Clinical Interaction Drug-Supplement

8/9/2019 Clinical Interaction Drug-Supplement

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Interactions in Clinical Practice:

Drug-Supplement, Drug-Nutrient

Leo Galland, M.D.

Applied Nutrition, Inc.www.nutritionwors!op.com


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"#er#iew

"$ almost %&& drugs and $i'ed-drugcom(inations used in t!e ).S.:

* Almost +&& ma deplete speci$ic nutrients.* "#er +&& ma interact wit! $ood or $ood

components.

* "#er && !a#e (een s!own to interact wit!dietar supplements, wit! ad#erse and (ene$icial interactions euall common.


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/pes o$ Interactions

* Pharmacodynamic: two su(stances e'!i(it

p!armacologic actions t!at rein$orce or

inter$ere wit! eac! ot!er0s actions.

* Pharmacokinetic: t!e a(sorption,

distri(ution, e'cretion or en1matic

trans$ormation o$ one su(stance is altered ( anot!er. Most ad#erse interactions are o$

t!is tpe.


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P!armacoinetic Mec!anisms

* Alteration o$ gastrointestinal or urinar p2.

* Stimulation, induction or in!i(ition o$

en1mes in#ol#ed in (iotrans$ormation or

transport o$ drugs or nutrients .

* Displacement o$ a drug $rom (inding to

plasma proteins.

* Alteration o$ solu(ilit.


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3$$ects o$ Interactions

* Nutrient depletion: Indi#idual nutrients ma !a#e

t!eir dietar reuirement increased ( speci$ic

drugs 4or supplements5.* Ad#erse: A speci$ic supplement ma undesira(l

decrease or increase t!e e$$ect o$ a drug or

supplement (eing taen.

* 6ene$icial: Drugs 4or supplements5 ma !a#e t!eir

actions en!anced or side e$$ects diminis!ed (

speci$ic supplements.


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Drug-Induced Nutrient Depletion

* A(out !al$ t!e drugs used in clinical

practice !a#e documented nutrient

depleting e$$ects.

* Co-en1me 78&, $olic acid, 69, 6, Mg, ;n

are nutrients most liel to (e depleted.

* Mec!anisms include impaired a(sorption or

(ioacti#ation< increased e'cretion.


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Co-en1me 78& Depletion

* Statin-induced co-7 depletion impairs

mitoc!ondrial $unction, raising t!e serum

lactate=pru#ate ratio. Sim#astatin (ut notator#astatin depletes mo$i(rillar co-7.

* Supplemental co-7, 8&& mg=da, pre#ents t!e

decline in serum co-7 le#els wit!out impairment

o$ t!e lipid-lowering e$$ect o$ statins and mare#erse smptoms o$ statin mopat!.


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Co-en1me 78& Depletion

4cont0d5* Statin-induced Co-7 depletion is increased (

#itamin 3 4>&& I)=da5.

* Co-7 is consumed in reccling tocop!erluinones (ac to tocop!erols.

* /!ia1ides, some (eta-(locers and man older

psc!otropic drugs !a#e (een s!own to inter$ere

wit! co-7 dependent en1mes, creating a possi(le

need $or co-7 supplementation in patients

recei#ing t!em.


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Are reported ad#erse

cardio#ascular e$$ects o$ #itamin3 supplements related to co-7

depletion in patients taing drugs

t!at inter$ere wit! co-7

snt!esis or co-7 dependent

en1mes?


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@itamin 3 and Statins

* a-/ocop!erol pre#ents statin (ene$its in people wit! low 2DL-C and normal /C.

* elated to tocop!erol in!i(ition o$ statin-induced ele#ation o$ 2DL9-C.

* Selenium 48&& mcg=da5 and $is! oil !a#e

t!e opposite e$$ect.* a-/ocop!erol depletes gamma-tocop!erol

( competiti#e (inding to transport protein.


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Clinicall Signi$icant Depletions-8

* Adriamcin depletes co-en1me 78&.

Cardioto'icit is reduced ( co-7 and

proprionl-L-carnitine.* Cisplatin depletes Mg. Nep!troto'icit is

reduced ( i.#. and oral Mg 48& mg tid5.

* /!ia1ides and B-ASA deri#ati#es deplete$olate, raising !omocsteine concentration.


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Clinicall Signi$icant Depletions-9

* Loop diuretics increase e'cretion o$ , Ca,

Mg, ;n, 68, 6, C. Correcting 68 de$icit

impro#es cardiac $unction o$ C2 patients.

* Cep!alosporins 4parenteral5 can deplete

#itamin 9, causing !emorr!age.

* Steroids deplete Ca and Mg, causing (oneloss. e#ersi(le wit! calcium and #it D.


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Antiretro#iral Nutrient Depletion

* A;/ depletes muscle carnitine and

increases lmp!octe apoptosis. e#ersed

wit! carnitine supplementation.

* A;/ is associated wit! decreased serum

1inc and copper< 1inc 9&& mg=da reduced

Candida and Pneumocstis in$ections in patients taing A;/.


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P!entoin-induced Depletions

* P!entoin ma deplete (iotin, $olate,

t!iamine, #itamin D 4causing !pocalcemia

and osteomalacia and #itamin .

* Memor impairment is associated wit!

reduced 6C $olate. olic acid, 8 mg=da,

pre#ents de$icienc wit!out ad#ersela$$ecting p!entoin meta(olism.


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@alproic Acid Depletions

* @alproate depletes carnitine, raisingammonia< re#ersed wit! carnitine 9 g=da.

* @alproate acid lowers serum $olate and PBP,raising !omocsteine< re#ersed wit! +&&mcg $olate, 89& mg 6 and >B mg 69.

* @alproate in!i(its (iotinidase. 6iotin 8&mg=da re#erses #alproate-associated !airloss and dermatitis in c!ildren.


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C!elation and Drug A(sorption

* C!elation ( minerals impairs a(sorption o$

uinolone or tetraccline anti(iotics,

t!roid, (isp!osp!onates, L-D"PA, someAC3 in!i(itors.

* 3#en some !er(s lie dandelion and $ennel,

can (e so ric! in minerals t!at t!e in!i(ita(sorption o$ t!ese same drugs.

.


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/!e Ctoc!rome P+B& Sstem and

Drug-Supplement Interactions* 3'pressed c!ie$l in li#er, intestines, lungs

and idnes 4EP!ase 8 deto'icationF5.

* 9& di$$erent !uman CPs, grouped (

amino acid !omolog, not ( $unction.

* CP8A9, CP9C%, CP9C8%, CP9D,

CP938 and CPA+ most important $oro'idation o$ drugs, 'eno(iotics.


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CP8A9

* Li#er onl. Inacti#ates ca$$eine and

(ioacti#ates aromatic and !eterocclic

amines< large inter-indi#idual di$$erences4up to 8&&-$old5. Induced ( c!ar-(roiled

meat, cigarettes, pollutants, dio'ins and

cruci$erous #egeta(les.


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CP9: Drug-Drug Interactions

* CP9C% accounts $or &H o$ CP acti#it in!uman li#er. Ma (e modi$ied ( Gingo (ilo(a.

* CP9C8% is primaril !epatic. P!enotpe re$lectst!e interaction o$ gene alleles.

* CP9D is e'tra-!epatic. 6ioacti#atescodeine=codones. BB alleles.

* CP938 in li#er, lung, (rain meta(oli1es organic

sol#ents lie et!anol. Induced wit! c!ronic et!anoluse, $asting, o(esit. In!i(ited ( acute alco!olintae, tea, (roccoli, garlic, onion, watercress.


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CPA+

* Li#er and small intestine.

* /rans$orms a(out B&H o$ common drugs.

* Induced ( St. Jo!n0s wort 4li#er, intestine5and 3c!inacea 4li#er onl5.

* In!i(ited ( peppermint oil and piperine.

* Intestinal (ut not li#er CPA+ is in!i(ited ( grape$ruit Kuice, Se#ille orange Kuice and3c!inacea.


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CPA+ and St. Jo!n0s ort

* CPA+ stimulation ( St. Jo!n0s wort

reduces (lood le#els o$ (en1odia1epines,

calcium c!annel (locers, anti-retro#irals,estrogens 4including "CPs5, amitriptline,

cclosporine, met!adone, tacrolimus and

possi(l war$arin.


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Intestinal CPA+ In!i(ition

* Increases (lood le#els o$ amiodarone,

artemisinin, ator#astatin, (uspirone,

car(ema1epine, cclosporine, dia1epam,diltia1em, ert!romcin, estradiol,

$elodipine, $entanl, $luo'etine, lo#astatin,

met!l-prednisolone, ni$edipine,nimodipine, pra1iuantel, sauina#ir,

sertraline, sildena$il, sim#astatin, #erapamil


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P-glcoprotein /ransporter 4P-gp5

* 3Kects 'eno(iotics $rom cells and causes (ac$low o$ some drugs $rom intestinal

mucosa into t!e lumen.* Produces multi-drug resistance to cancer

c!emot!erap.

* In!i(ited ( piperine, mil t!istle andacutel ( St. Jo!n0s wort.

* Stimulated ( continued St. Jo!n0s wort.


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Alteration o$ Intestinal CPA+

and=or P-glcoprotein* "$ten in#ol#es t!e same su(strates.

* Primaril e$$ects drugs t!at pass slowl

t!roug! intestinal mucosa.

* Interactions in vivo ma not (e predicted (

interactions in vitro.


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Ad#erse P!armacodnamic

Interactions* B-2/P and SSI0s

* Licorice and !orsetail, diuretics or la'ati#es

* P!enlalanine or a#a and neuroleptics

* 6ee #enom and AC3 in!i(itors

* 6rewer0s east and MA" in!i(itors* Inter$eron-alp!a and (upleurum


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Antit!rom(otic Interactions

* B natural products in!i(it platelet $unction

in vivo $ollowing oral use. /!e ma

rein$orce eac! ot!er or interact wit!antit!rom(otic medication.

* Aspirin-#itamin 3 interaction: aspirin

in!i(its platelet aggregation< #itamin 3in!i(its platelet ad!esion to endot!elium.


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Aspirin-@itamin 3 Interactions

* a-/ocop!erol 4B& I)=da5 raised ris o$ gingi#al (leeding 9BH among ASA users.

* +&& I)=da a-tocop!erol added to 9B mg ASA=dareduced incidence o$ /IAs compared to aspirinalone.

* @it 3 B& I)=da, decreased isc!emic stroe ( &H

(ut increased !emorr!agic stroe ( 8+BH in!pertensi#e, non-dia(etic male smoers. India(etics, t!ere was no increase in !emorr!agicstroe and isc!emic stroe decreased ( >&H.


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ar$arin Interactions

* +% natural products ma inter$ere wit!war$arin< 98 con$irmed, 9 possi(le.

* 2er(al coumarins mig!t compete $or (inding to plasma protein, increasing plasma $ree war$arin concentration.

* Controlled studies $ound no e$$ect on#itamin 3 or coen1me 78& on IN o$ patients taing war$arin.


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6ene$icial Drug-Supplement

Interactions* e$lect additi#e=complementar e$$ects o$

supplements and drugs, or amelioration o$

to'ic drug e$$ects ( supplements.* is! oils en!ance anti-in$lammator,

antiarr!t!mic, anti-lipemic, antidepressant,

and neuroleptic drugs, (eta-(locers,lit!ium and insulin. 3PA and D2A ma

!a#e di$$erential e$$ects.


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Acetaminop!en /o'icit

* Protecti#e supplements:

N-acetl csteine 4clinical use5

L-met!ionine and SAMe

Mil t!istle

Andrograp!isSc!isandra


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ASA=NSAID Gastropat!

* Protecti#e supplements 4!uman trials5:

@it C 4B&&-8&&& mg (id5

SAMe B&& mg=da

Caenne 9& grams

Deglcrr!i1inated licorice B& mg tid

Colostrum 89B mg tid


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Neuroleptic Side 3$$ects


@itamin 3 89&&-8&& I)=da 4/.D.5

6ranc!ed c!ain amino acids 4/.D.5Gingo (ilo(a B& mg=da

Sarcosine 4N-C2-glcine5 9 gm=da

3icosapentaenoate 43PA5 9 gm=da

Glcine &.+-&. mg=g=da


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Cisplatin /o'icit


6ismut! 8B& mg=g=da 8&das

Gingo (ilom(a 8&& mg=g single dose

Glutat!ione B gm i.#.

MgS"+ gm i.#.= Mg 8& mg tid

Sili(inin 9&& mg=g i.#. single dose

N-acetl csteine gm=da

Selenium +&&& mcg=da das

@itamin C B&-9&& mg=g i.#. single dose

@itamin 3 && I)=da till mont!s post-c!emot!erap


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More Antineoplastic /o'icit

* Protecti#e supplements

@itamin 6 B& mg tid

Glutamine & gm=daMelatonin 9& mg 2S

Coriolus #ersicolor 8 gm tid

/!eanine 4in #itro5Inositol !e'ap!osp!ate 4IP5 4in #itro5

Calcium D-glucarate 4in #itro5


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is! oils, NSAIDs, ASA

* 9&& mg o$ 3PA D2A $or mont!s allow NSAID reduction in r!eumatoid art!ritis.

Plasma p!osp!olipid 3PA must reac! BH.* is! oil & ml=da re#ersed ASA0s increase

o$ L/6+ snt!esis< no !emorr!age.

* ASA increases snt!esis o$ anti-in$lammator resol#ins and protectins $romD2A in #itro ( acetlating C"-9.


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Conclusion

* Almost !al$ t!e drugs commonl used in t!e)S ma deplete speci$ic nutrients, creating a

need $or nutritional supplementation.* Ad#erse interactions !a#e recei#ed e'tensi#e

press co#erage.

* 6ene$icial drug-supplement interactions areat least as important and permit creati#enutritional t!erapies.

Documents

Clinical Interaction Drug-Supplement