73
8/13/2019 Drug Induced Nutrient Depletion http://slidepdf.com/reader/full/drug-induced-nutrient-depletion 1/73 Drug-Herb/Drug-Nutrient Interactions & Depletions Mario Roxas, ND ACHS 2010 Portland, OR

Drug Induced Nutrient Depletion

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Page 1: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 173

Drug-HerbDrug-Nutrient

Interactions amp Depletions

Mario Roxas NDACHS 2010

Portland OR

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 373

144million

Source Health United States 2009 table 95httpwwwcdcgovnchsdatahushus09pdf095

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 473

$287billion

Source Consumer Reports

httpwwwconsumerreportsorghealthprescription-

drugsbest-drugs-for-lessoverviewbest-drugs-for-lesshtm

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 573

$94billion

Source Nutritional Supplements in the US 4th Edition

httpwwwpackagedfactscomNutritional-Supplements-Edition-2642045

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 673

Top 20 Prescription Drugs in 2009in units sold

1 Lipitor

2 Nexium

3 Plavix

4 Singulair5 Lexapro

6 Pro-Air HFA

7 Synthroid

8 Crestor9 Advair Diskus

10Diovan

11 Cymbalta

12 Effexor XR

13 Klor-Con

14 Prevacid15 Diovan HCT

16 Actos

17 Flomax

18 Seroquel19 Levaquin

20 Tricor

(httpwwwdrugscomtop200_unitshtml)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 773

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Clinical Indication

bull Cholesterol-lowering medication

Actionbull Inhibits HMG CoA Reductase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 873

Tricor(fenofibrate)

Clinical Indication

bull Cholesterol-lowering medication

Action

bull Fibrate ndash Peroxisome proliferator-activated receptoralpha (PPAR-α) agonist

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 973

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1073

HMG-CoA Reductase

Pathway

Source enImageHMG-CoA_reductase_pathwaypng

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1173

PPAR-alpha Pathway

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1273

CoQ10

Nutrient Depletion

bull Coenzyme Q10

ndash Decreases CoQ10 serumlevels

ndash Consider supplementation

w CoQ10

ndash 100 mgday prevented

Q10 drop

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1373

Statins can reduce serum levels of

coenzyme Q 10 by up to 40

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1473

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Nutrient Interaction

bull Niacin ndash Concomitant use may increase potential for myopathies

bullL-Arginine ndash Coadministration may enhance triglyceride-lowering effect

bull Vitamin A ndash Higher blood vitamin A levels found in individuals taking

HMG CoA reductase inhibitors for 2 years

ndash Unknown mechanism (hepatic storage)

bull Vitamin D ndash Deficiency may increase risk of myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 2: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 373

144million

Source Health United States 2009 table 95httpwwwcdcgovnchsdatahushus09pdf095

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 473

$287billion

Source Consumer Reports

httpwwwconsumerreportsorghealthprescription-

drugsbest-drugs-for-lessoverviewbest-drugs-for-lesshtm

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 573

$94billion

Source Nutritional Supplements in the US 4th Edition

httpwwwpackagedfactscomNutritional-Supplements-Edition-2642045

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 673

Top 20 Prescription Drugs in 2009in units sold

1 Lipitor

2 Nexium

3 Plavix

4 Singulair5 Lexapro

6 Pro-Air HFA

7 Synthroid

8 Crestor9 Advair Diskus

10Diovan

11 Cymbalta

12 Effexor XR

13 Klor-Con

14 Prevacid15 Diovan HCT

16 Actos

17 Flomax

18 Seroquel19 Levaquin

20 Tricor

(httpwwwdrugscomtop200_unitshtml)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 773

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Clinical Indication

bull Cholesterol-lowering medication

Actionbull Inhibits HMG CoA Reductase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 873

Tricor(fenofibrate)

Clinical Indication

bull Cholesterol-lowering medication

Action

bull Fibrate ndash Peroxisome proliferator-activated receptoralpha (PPAR-α) agonist

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 973

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1073

HMG-CoA Reductase

Pathway

Source enImageHMG-CoA_reductase_pathwaypng

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1173

PPAR-alpha Pathway

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1273

CoQ10

Nutrient Depletion

bull Coenzyme Q10

ndash Decreases CoQ10 serumlevels

ndash Consider supplementation

w CoQ10

ndash 100 mgday prevented

Q10 drop

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1373

Statins can reduce serum levels of

coenzyme Q 10 by up to 40

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1473

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Nutrient Interaction

bull Niacin ndash Concomitant use may increase potential for myopathies

bullL-Arginine ndash Coadministration may enhance triglyceride-lowering effect

bull Vitamin A ndash Higher blood vitamin A levels found in individuals taking

HMG CoA reductase inhibitors for 2 years

ndash Unknown mechanism (hepatic storage)

bull Vitamin D ndash Deficiency may increase risk of myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 3: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 373

144million

Source Health United States 2009 table 95httpwwwcdcgovnchsdatahushus09pdf095

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 473

$287billion

Source Consumer Reports

httpwwwconsumerreportsorghealthprescription-

drugsbest-drugs-for-lessoverviewbest-drugs-for-lesshtm

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 573

$94billion

Source Nutritional Supplements in the US 4th Edition

httpwwwpackagedfactscomNutritional-Supplements-Edition-2642045

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 673

Top 20 Prescription Drugs in 2009in units sold

1 Lipitor

2 Nexium

3 Plavix

4 Singulair5 Lexapro

6 Pro-Air HFA

7 Synthroid

8 Crestor9 Advair Diskus

10Diovan

11 Cymbalta

12 Effexor XR

13 Klor-Con

14 Prevacid15 Diovan HCT

16 Actos

17 Flomax

18 Seroquel19 Levaquin

20 Tricor

(httpwwwdrugscomtop200_unitshtml)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 773

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Clinical Indication

bull Cholesterol-lowering medication

Actionbull Inhibits HMG CoA Reductase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 873

Tricor(fenofibrate)

Clinical Indication

bull Cholesterol-lowering medication

Action

bull Fibrate ndash Peroxisome proliferator-activated receptoralpha (PPAR-α) agonist

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 973

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1073

HMG-CoA Reductase

Pathway

Source enImageHMG-CoA_reductase_pathwaypng

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1173

PPAR-alpha Pathway

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1273

CoQ10

Nutrient Depletion

bull Coenzyme Q10

ndash Decreases CoQ10 serumlevels

ndash Consider supplementation

w CoQ10

ndash 100 mgday prevented

Q10 drop

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1373

Statins can reduce serum levels of

coenzyme Q 10 by up to 40

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1473

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Nutrient Interaction

bull Niacin ndash Concomitant use may increase potential for myopathies

bullL-Arginine ndash Coadministration may enhance triglyceride-lowering effect

bull Vitamin A ndash Higher blood vitamin A levels found in individuals taking

HMG CoA reductase inhibitors for 2 years

ndash Unknown mechanism (hepatic storage)

bull Vitamin D ndash Deficiency may increase risk of myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 4: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 473

$287billion

Source Consumer Reports

httpwwwconsumerreportsorghealthprescription-

drugsbest-drugs-for-lessoverviewbest-drugs-for-lesshtm

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 573

$94billion

Source Nutritional Supplements in the US 4th Edition

httpwwwpackagedfactscomNutritional-Supplements-Edition-2642045

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 673

Top 20 Prescription Drugs in 2009in units sold

1 Lipitor

2 Nexium

3 Plavix

4 Singulair5 Lexapro

6 Pro-Air HFA

7 Synthroid

8 Crestor9 Advair Diskus

10Diovan

11 Cymbalta

12 Effexor XR

13 Klor-Con

14 Prevacid15 Diovan HCT

16 Actos

17 Flomax

18 Seroquel19 Levaquin

20 Tricor

(httpwwwdrugscomtop200_unitshtml)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 773

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Clinical Indication

bull Cholesterol-lowering medication

Actionbull Inhibits HMG CoA Reductase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 873

Tricor(fenofibrate)

Clinical Indication

bull Cholesterol-lowering medication

Action

bull Fibrate ndash Peroxisome proliferator-activated receptoralpha (PPAR-α) agonist

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 973

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1073

HMG-CoA Reductase

Pathway

Source enImageHMG-CoA_reductase_pathwaypng

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1173

PPAR-alpha Pathway

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1273

CoQ10

Nutrient Depletion

bull Coenzyme Q10

ndash Decreases CoQ10 serumlevels

ndash Consider supplementation

w CoQ10

ndash 100 mgday prevented

Q10 drop

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1373

Statins can reduce serum levels of

coenzyme Q 10 by up to 40

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1473

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Nutrient Interaction

bull Niacin ndash Concomitant use may increase potential for myopathies

bullL-Arginine ndash Coadministration may enhance triglyceride-lowering effect

bull Vitamin A ndash Higher blood vitamin A levels found in individuals taking

HMG CoA reductase inhibitors for 2 years

ndash Unknown mechanism (hepatic storage)

bull Vitamin D ndash Deficiency may increase risk of myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 5: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 573

$94billion

Source Nutritional Supplements in the US 4th Edition

httpwwwpackagedfactscomNutritional-Supplements-Edition-2642045

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 673

Top 20 Prescription Drugs in 2009in units sold

1 Lipitor

2 Nexium

3 Plavix

4 Singulair5 Lexapro

6 Pro-Air HFA

7 Synthroid

8 Crestor9 Advair Diskus

10Diovan

11 Cymbalta

12 Effexor XR

13 Klor-Con

14 Prevacid15 Diovan HCT

16 Actos

17 Flomax

18 Seroquel19 Levaquin

20 Tricor

(httpwwwdrugscomtop200_unitshtml)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 773

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Clinical Indication

bull Cholesterol-lowering medication

Actionbull Inhibits HMG CoA Reductase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 873

Tricor(fenofibrate)

Clinical Indication

bull Cholesterol-lowering medication

Action

bull Fibrate ndash Peroxisome proliferator-activated receptoralpha (PPAR-α) agonist

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 973

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1073

HMG-CoA Reductase

Pathway

Source enImageHMG-CoA_reductase_pathwaypng

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1173

PPAR-alpha Pathway

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1273

CoQ10

Nutrient Depletion

bull Coenzyme Q10

ndash Decreases CoQ10 serumlevels

ndash Consider supplementation

w CoQ10

ndash 100 mgday prevented

Q10 drop

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1373

Statins can reduce serum levels of

coenzyme Q 10 by up to 40

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1473

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Nutrient Interaction

bull Niacin ndash Concomitant use may increase potential for myopathies

bullL-Arginine ndash Coadministration may enhance triglyceride-lowering effect

bull Vitamin A ndash Higher blood vitamin A levels found in individuals taking

HMG CoA reductase inhibitors for 2 years

ndash Unknown mechanism (hepatic storage)

bull Vitamin D ndash Deficiency may increase risk of myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 6: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 673

Top 20 Prescription Drugs in 2009in units sold

1 Lipitor

2 Nexium

3 Plavix

4 Singulair5 Lexapro

6 Pro-Air HFA

7 Synthroid

8 Crestor9 Advair Diskus

10Diovan

11 Cymbalta

12 Effexor XR

13 Klor-Con

14 Prevacid15 Diovan HCT

16 Actos

17 Flomax

18 Seroquel19 Levaquin

20 Tricor

(httpwwwdrugscomtop200_unitshtml)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 773

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Clinical Indication

bull Cholesterol-lowering medication

Actionbull Inhibits HMG CoA Reductase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 873

Tricor(fenofibrate)

Clinical Indication

bull Cholesterol-lowering medication

Action

bull Fibrate ndash Peroxisome proliferator-activated receptoralpha (PPAR-α) agonist

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 973

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1073

HMG-CoA Reductase

Pathway

Source enImageHMG-CoA_reductase_pathwaypng

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1173

PPAR-alpha Pathway

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1273

CoQ10

Nutrient Depletion

bull Coenzyme Q10

ndash Decreases CoQ10 serumlevels

ndash Consider supplementation

w CoQ10

ndash 100 mgday prevented

Q10 drop

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1373

Statins can reduce serum levels of

coenzyme Q 10 by up to 40

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1473

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Nutrient Interaction

bull Niacin ndash Concomitant use may increase potential for myopathies

bullL-Arginine ndash Coadministration may enhance triglyceride-lowering effect

bull Vitamin A ndash Higher blood vitamin A levels found in individuals taking

HMG CoA reductase inhibitors for 2 years

ndash Unknown mechanism (hepatic storage)

bull Vitamin D ndash Deficiency may increase risk of myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 7: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 773

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Clinical Indication

bull Cholesterol-lowering medication

Actionbull Inhibits HMG CoA Reductase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 873

Tricor(fenofibrate)

Clinical Indication

bull Cholesterol-lowering medication

Action

bull Fibrate ndash Peroxisome proliferator-activated receptoralpha (PPAR-α) agonist

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 973

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1073

HMG-CoA Reductase

Pathway

Source enImageHMG-CoA_reductase_pathwaypng

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1173

PPAR-alpha Pathway

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1273

CoQ10

Nutrient Depletion

bull Coenzyme Q10

ndash Decreases CoQ10 serumlevels

ndash Consider supplementation

w CoQ10

ndash 100 mgday prevented

Q10 drop

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1373

Statins can reduce serum levels of

coenzyme Q 10 by up to 40

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1473

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Nutrient Interaction

bull Niacin ndash Concomitant use may increase potential for myopathies

bullL-Arginine ndash Coadministration may enhance triglyceride-lowering effect

bull Vitamin A ndash Higher blood vitamin A levels found in individuals taking

HMG CoA reductase inhibitors for 2 years

ndash Unknown mechanism (hepatic storage)

bull Vitamin D ndash Deficiency may increase risk of myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 8: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 873

Tricor(fenofibrate)

Clinical Indication

bull Cholesterol-lowering medication

Action

bull Fibrate ndash Peroxisome proliferator-activated receptoralpha (PPAR-α) agonist

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 973

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1073

HMG-CoA Reductase

Pathway

Source enImageHMG-CoA_reductase_pathwaypng

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1173

PPAR-alpha Pathway

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1273

CoQ10

Nutrient Depletion

bull Coenzyme Q10

ndash Decreases CoQ10 serumlevels

ndash Consider supplementation

w CoQ10

ndash 100 mgday prevented

Q10 drop

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1373

Statins can reduce serum levels of

coenzyme Q 10 by up to 40

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1473

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Nutrient Interaction

bull Niacin ndash Concomitant use may increase potential for myopathies

bullL-Arginine ndash Coadministration may enhance triglyceride-lowering effect

bull Vitamin A ndash Higher blood vitamin A levels found in individuals taking

HMG CoA reductase inhibitors for 2 years

ndash Unknown mechanism (hepatic storage)

bull Vitamin D ndash Deficiency may increase risk of myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 9: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 973

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1073

HMG-CoA Reductase

Pathway

Source enImageHMG-CoA_reductase_pathwaypng

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1173

PPAR-alpha Pathway

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1273

CoQ10

Nutrient Depletion

bull Coenzyme Q10

ndash Decreases CoQ10 serumlevels

ndash Consider supplementation

w CoQ10

ndash 100 mgday prevented

Q10 drop

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1373

Statins can reduce serum levels of

coenzyme Q 10 by up to 40

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1473

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Nutrient Interaction

bull Niacin ndash Concomitant use may increase potential for myopathies

bullL-Arginine ndash Coadministration may enhance triglyceride-lowering effect

bull Vitamin A ndash Higher blood vitamin A levels found in individuals taking

HMG CoA reductase inhibitors for 2 years

ndash Unknown mechanism (hepatic storage)

bull Vitamin D ndash Deficiency may increase risk of myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 10: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1073

HMG-CoA Reductase

Pathway

Source enImageHMG-CoA_reductase_pathwaypng

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1173

PPAR-alpha Pathway

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1273

CoQ10

Nutrient Depletion

bull Coenzyme Q10

ndash Decreases CoQ10 serumlevels

ndash Consider supplementation

w CoQ10

ndash 100 mgday prevented

Q10 drop

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1373

Statins can reduce serum levels of

coenzyme Q 10 by up to 40

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1473

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Nutrient Interaction

bull Niacin ndash Concomitant use may increase potential for myopathies

bullL-Arginine ndash Coadministration may enhance triglyceride-lowering effect

bull Vitamin A ndash Higher blood vitamin A levels found in individuals taking

HMG CoA reductase inhibitors for 2 years

ndash Unknown mechanism (hepatic storage)

bull Vitamin D ndash Deficiency may increase risk of myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 11: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1173

PPAR-alpha Pathway

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1273

CoQ10

Nutrient Depletion

bull Coenzyme Q10

ndash Decreases CoQ10 serumlevels

ndash Consider supplementation

w CoQ10

ndash 100 mgday prevented

Q10 drop

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1373

Statins can reduce serum levels of

coenzyme Q 10 by up to 40

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1473

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Nutrient Interaction

bull Niacin ndash Concomitant use may increase potential for myopathies

bullL-Arginine ndash Coadministration may enhance triglyceride-lowering effect

bull Vitamin A ndash Higher blood vitamin A levels found in individuals taking

HMG CoA reductase inhibitors for 2 years

ndash Unknown mechanism (hepatic storage)

bull Vitamin D ndash Deficiency may increase risk of myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 12: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1273

CoQ10

Nutrient Depletion

bull Coenzyme Q10

ndash Decreases CoQ10 serumlevels

ndash Consider supplementation

w CoQ10

ndash 100 mgday prevented

Q10 drop

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1373

Statins can reduce serum levels of

coenzyme Q 10 by up to 40

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1473

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Nutrient Interaction

bull Niacin ndash Concomitant use may increase potential for myopathies

bullL-Arginine ndash Coadministration may enhance triglyceride-lowering effect

bull Vitamin A ndash Higher blood vitamin A levels found in individuals taking

HMG CoA reductase inhibitors for 2 years

ndash Unknown mechanism (hepatic storage)

bull Vitamin D ndash Deficiency may increase risk of myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 13: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1373

Statins can reduce serum levels of

coenzyme Q 10 by up to 40

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1473

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Nutrient Interaction

bull Niacin ndash Concomitant use may increase potential for myopathies

bullL-Arginine ndash Coadministration may enhance triglyceride-lowering effect

bull Vitamin A ndash Higher blood vitamin A levels found in individuals taking

HMG CoA reductase inhibitors for 2 years

ndash Unknown mechanism (hepatic storage)

bull Vitamin D ndash Deficiency may increase risk of myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 14: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1473

Lipitor (atorvastatin)

Crestor (rosuvastatin)

Nutrient Interaction

bull Niacin ndash Concomitant use may increase potential for myopathies

bullL-Arginine ndash Coadministration may enhance triglyceride-lowering effect

bull Vitamin A ndash Higher blood vitamin A levels found in individuals taking

HMG CoA reductase inhibitors for 2 years

ndash Unknown mechanism (hepatic storage)

bull Vitamin D ndash Deficiency may increase risk of myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 15: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1573

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 16: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1673

Statins and Niacin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 17: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1773

Statins and L-Arginine

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 18: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1873

Low Vitamin D a Cause of Statin-induced Myositis-Myalgia

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 19: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 1973

Tricor(fenofibrate)

Nutrient Interaction

bull CoQ10

- May deplete natural stores

- Concurrent supplementation may be

beneficial

bull Vitamin E

- May deplete natural stores in liver

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 20: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2073

Tricor (fenofibrate) and CoQ10

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 21: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2173

Tricor (fenofibrate) and vitamin E

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 22: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2273

Red Yeast Rice(Monascus purpureus)

Monacolin K (aka mevinolin)

The HMG-CoA reductase activity of red yeast ricecomes from a family of naturally occurringsubstances called monacolins

Monacolin K is the ingredient in red yeast rice thatMerck amp Co pharmaceutical manufacturer ofMevacorsbquo (lovastatin) asserts is a patentedpharmaceutical

However red yeast rice contains a family of ninedifferent monacolins all of which have the ability to

inhibit HMG-CoA reductase

Other active ingredients in red yeast rice includesterols (betasitosterol campesterol stigmasterolsapogenin) isoflavones and monounsaturated fattyacids

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 23: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 24: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2473

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 25: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2573

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 26: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2673

Nexium (esomeprazole)

Prevacid (lansoprazole)

Clinical Indication

bull Hyperchlorhydria GERD

Action

bull Proton Pump Inhibitors

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 27: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2773

Nexium (esomeprazole)

Prevacid (lansoprazole)

Nutrient Depletion

bull Beta Carotene

bullVitamin B12

bull Folates

bull Calcium

bull Chromium

bull

Copperbull Iron

bull Selenium

bull Zinc

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 28: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2873

Plavix(clopidrogrel)

Clinical Indication

bull StrokeMI Prevention

Action

bull Anti-platelet agent -

Specifically inhibits P2Y12 ADP

receptors involved in platelet

aggregation

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 29: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 2973

Plavix

(clopidrogrel)Nutrient Interaction

Depletion

bull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 30: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3073

Warfarin-induced Atherosclerosis

In rats arterial calcification was induced by warfarin and reversed by vitamin K

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 31: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3173

Warfarin-induced Atherosclerosis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 32: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3273

Is Vitamin K Really Contraindicated with Warfarin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 33: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3373

Is Conventional Wisdom Really Wise

bull double-blind 6-month RCT

bull n=70 patients on warfarin

with unstable anticoagulation

bull 150 mcgday vit K or placebo

bullK supplementation resulted in

significant decrease in

variation of INR

bullK supplementation alsoresulted in sig increase in of

time within target INR range

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 34: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3473

Is Conventional Wisdom Really Wise

Conclusion Small series of 8 patients poorly controlled on warfarin 100 mcg K

daily ldquosignificantly increased the number of INRs in range as well as the time in

range and decreased INR fluctuation in this small series of selected patientsrdquo

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 35: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3573

Bottom line on Vitamin K and Anticoagulants

Wise to avoid high doses of vitamin K in patients on

anticoagulant therapy

Low-dose ndash 100-150 mcg ndash may actually benefit

patients on warfarin

Need to do in conjunction with prescribing doctoras would need to adjust warfarin dose accordingly

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 36: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3673

Seroquel

(quetiapine)

Clinical Indication

bull Schizophrenia Bipolar

Disorder Depression

Action

bull

Atypical antipsychotic

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 37: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3773

Seroquel(quetiapine)

Nutrient InteractionDepletion

bull No established cases

bull But one food to avoid isgrapefruit

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 38: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3873

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Indication

bull Depression

bull Anxietybull Peripheral

neuropathy

(Cymbalta)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 39: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 3973

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

Action

bull Selective Serotonin

Reuptake Inhibitor(SSRI) Selective

Serotonin and

Norepinephrine

Reuptake Inhibitor(SSNRI)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 40: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4073

Lexapro (escitalopram)Cymbalta

(duloxetine)Effexor XR (venlafaxine)

HerbNutrient Interactions

bull St Johns wort

bull 5-HTPL-tryptophan

bull Chromium

bull Zincbull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 41: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4173

ldquoI want a new drugrdquo- Huey Lewis

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 42: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4273

5-MTHF(5-methyltetrahydrofolate)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 43: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4373

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 44: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4473

5-MTHF

(5-methyltetrahydrofolate)

bull J Clin Psychopharmacol 2003 Jun23(3)309-13

bull Prediction of treatment response in geriatric depression frombaseline folate level interaction with an SSRI or a tricyclicantidepressant

bull Alpert M Silva RR Pouget ER

bull

Department of Psychiatry New York University Medical Center 550First Avenue New York NY 10016 USA

bull Abstract

bull Depressed geriatric patients have lower levels of folate (FOL) thancontrols Also FOL supplement can reduce depressive morbidityOne hypothesis consistent with this is that FOL deficiency causes alowering of CNS serotonin that contributes to depression Thepresent report is from one site of a multicenter study that comparedan SSRI (sertraline) with a nonspecific tricyclic antidepressant(nortriptyline) in geriatric depressed patients We added measures ofFOL at baseline and outcome for 22 depressed patients older than 60years Both treatments were effective At baseline FOL levels werewithin the normal range Higher FOL levels at baseline predictedgreater improvement Further study of FOL interaction with SSRI iswarranted For the group treated with the SSRI baseline FOL levelwas a more efficient predictor of improvement especially for resultson a self-rating depression scale (POMS)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 45: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4573

5-MTHF

(5-methyltetrahydrofolate)

Ann Clin Psychiatry 2002 Mar14(1)33-8

Folinic acid (Leucovorin) as an adjunctive treatment for

SSRI-refractory depressionAlpert JE Mischoulon D Rubenstein GE Bottonari K Nierenberg AA Fava MDepression Clinical and Research Program Department of Psychiatry Massachusetts

General Hospital Boston 02114 USA jalpertpartnersorg

Abstract

Low folate is associated with poorer response to selective serotonin reuptake

inhibitors (SSRIs) in major depressive disorder (MDD) Folate supplementation

in MDD has been studied in other settings with promising results The

objective of this study was to assess the efficacy of methylfolate as an

adjunctive treatment among adults with MDD and inadequate response to an

SSRI Twenty-two adults (59 female mean age 452 +- 110 years) withDSM-IV MDD partial or nonresponse to an SSRI after at least 4 weeks of

treatment and a 17-item Hamilton Depression Rating Scale (HAM-D-17) score

gt or = 12 were enrolled in this 8-week prospective open trial Exclusion criteria

included current use of anticonvulsants or psychotropics other than an SSRI or

B12 deficiency Leucovorin (folinic acid) which is metabolized to methylfolate

was added to SSRIs at 15-30 mgday Folate levels rose from 28 +- 19 ngmL

to 301 +- 203 ngmL (p lt 0001) HAM-D-17 scores among the 16 completers

decreased from 191 +- 39 to 128 +- 70 (p lt 001) However only 31 of

- -

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 46: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4673

Singulair

(montelukast)

Indication

bull Asthma

bull Seasonal Allergies

Action

bull Leukotriene inhibitor

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 47: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4773

Singulair(montelukast)

Nutrient Interaction

Depletion

bull

No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 48: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4873

ProAir HFA(albuterol inhalation)

Indication

bull AsthmaCOPD

Action

bull Beta-II-adrenoceptor agonistbronchodilator

Nutrient InteractionDepletion

bull

Calciumbull Magnesium

bull Potassium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 49: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 4973

Advair Diskus(fluticasone and salmenterol)

Indication

bull AsthmaCOPD

Actionbull Corticosteroidbeta-agonist

combination inhaler forbronchodilation and anti-

inflammatory supportNutrient Depletion

bull Calcium

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 50: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5073

Advair Diskus(fluticasone and salmenterol)

Nutrient Depletion (cont)

bull Magnseium

bull

Potassiumbull Selenium

bull Zinc

bull

Folatebull Vitamin C

bull Vitamin D

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 51: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5173

Synthroid(levothyroxine)

Indication

bull Hypothryoidism

Action

bull Synthetic thyroid hormone

Nutrient InteractionDepletion

bull Iron

bull Soybull Bugleweed (Lycopus spp)

bull Lemon Balm (Melissa officinalis)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 52: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5273

DiovanDiovan HCT(valsartan and hydrochlorothiazide)

Indication

bull Hypertension CHF post-MI

Action

bull

Angiotensin II receptor agonistthiazide diuretic combination

Nutrient Depletion

bull Magnesium

bull

Phosphorousbull Potassium

bull Sodium

bull Zinc

Di Di HCT

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 53: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5373

DiovanDiovan HCT

(valsartan and hydrochlorothiazide)

Pezza V Bernardini F Pezza E et al Am J Hypertens 1998111267-1270

Nutrient Interaction

bull L-Arginine

ndash Co-administration may

improve blood pressure in

essential hypertension

l

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 54: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5473

Indication

bull Hypokalemia

Action

bull Prevention of hypo-kalemia

Nutrient InteractionDepletion

bull No established cases

Klor-Con(potassium hydrochloride)

A

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 55: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5573

Indication

bull Anti-diabetic agent

Action

bull Thiazolidinedione

Nutrient InteractionDepletion

bull No established cases

Actos(pioglitazone)

Fl

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 56: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5673

Flomax(tamsulosin)

Indication

bull BPH

Action

bull Alpha-adrenergic blocker

Nutrient InteractionDepletionbull No established cases

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 57: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5773

L i

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 58: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5873

Action

bull

Antibiotic

Nutrient Depletion

bull Vitamin K

bull Magnesium

bull Quercetin

Levaquin(levofloxacin)

Nutrient DepletionInteractions

bull Bifidobacterium bifidum

bull Lactobacillus acidophilus

bull Biotin

bull B Vitamins

bull Calcium

bull Iron

Levaquin

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 59: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 5973

Levaquin

(levofloxacin)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 60: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6073

Lactobacillus sporogenesbull Spore-forming highly stable

Bacillus organism

bull Also known as Bacillus

coagulans

Saccharomyces boulardii

bull a subspecies of

Saccharomyces cervesiaebull Beneficial yeast for the GI

tract

Celebrex

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 61: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6173

Celebrex(celecoxib)

Indication

bull OsteoarthritisRheumatoidarthritis

Action

bull Sulfa non-steroidal anti-inflammatory drug (NSAID)

COX-2 InhibitorNutrient Depletion

bull Folate

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 62: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6273

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 63: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6373

THE CURCUMIN COMPLEX

Three main polyphenols

Curcumin I

Demethoxy-curcumin (Curcumin II)

Bis-demethoxy-curcumin (Curcumin III)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 64: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6473

THE CURCUMIN COMPLEX

Over 3000 scientific articles

Antioxidant

Anti-inflammatory Joint Protective

GI Protective

Modulates cholesterol

Improves blood vessel function

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 65: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6573

Extensive research within the past two decades has shown that curcuminmediates its anti-inflammatory effects through the down regulation of

inflammatory transcription factors (such as nuclear factor Kappa B) enzymes

(such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor

necrosis factor interleukin 1 and interleukin 6)

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 66: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6673

CURCUMIN

Anti-Inflammatory Mechanisms of Action

Inhibition of NF-kB Downregulation of COX-2

Inhibition of lipoxygenase

Inhibition of inducible nitric oxide synthase

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 67: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6773

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6973

CURCUMIN amp CANCER

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7073

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7173

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7273

Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

Page 68: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 6873

Aim A proprietary complex of curcumin with soy phosphatidylcholine (Merivareg Indena SpA) was evaluated

in a registry study to define its efficacy in 50 patients with osteoarthritis (OA) at dosages corresponding to

200 mg curcumin per diem

MethodsOA signssymptoms were evaluated by the WOMAC scores Mobility was studied by walking

performance (treadmill) and inflammatory status was assessed by measurementsof C-reactive protein (CRP)

Results After three months of treatment the global WOMAC score decreased by 58 (Plt005) walking

distance in the treadmill test was prolonged from 76 m to 332 m (Plt005) and CRP levels decreased from

168 plusmn 18 to 113 plusmn 41 mgL in the subpopulation with high CRP In comparison the control group

experienced only a modest improvement in these parameters (2 in the WOMAC score from 82 m to 129 m

in the treadmill

test and from 175 plusmn 123 to 112 plusmn 222 mgL in the CRP plasma concentration) while the treatment costs(use of anti-inflammatory drugs treatment and hospitalization) were reduced significantly in the treatment

group

Conclusion These results show that Merivareg is clinically effective in the management and treatment of

osteoarthritis and suggests that the increased stability and better absorption of curcumin induced by

complexation with phospholipids has clinical relevance and sets the stage for larger and more prolonged

studies

PANMINERVA MED 201052

50 patients

250 mg bid of curcuminphospholipid combo (200 mg

curcuminday)

Significant improvement in CRP

Significant improvement in walking distance

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CURCUMIN amp CANCER

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Conclusions

8132019 Drug Induced Nutrient Depletion

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Thank you

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CURCUMIN amp CANCER

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8132019 Drug Induced Nutrient Depletion

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8132019 Drug Induced Nutrient Depletion

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Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

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8132019 Drug Induced Nutrient Depletion

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8132019 Drug Induced Nutrient Depletion

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Conclusions

8132019 Drug Induced Nutrient Depletion

httpslidepdfcomreaderfulldrug-induced-nutrient-depletion 7373

Thank you

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8132019 Drug Induced Nutrient Depletion

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Conclusions

8132019 Drug Induced Nutrient Depletion

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Thank you

Page 72: Drug Induced Nutrient Depletion

8132019 Drug Induced Nutrient Depletion

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Conclusions

8132019 Drug Induced Nutrient Depletion

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Thank you

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8132019 Drug Induced Nutrient Depletion

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Thank you