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NUTRITION and PAIN

Presenter

Julie Besse B.Sc., Registered Dietitian (CDO) St. Joseph’s Care Group –Chronic Pain & Mental Health Programs

Certified in Nutritional Pain Management 2017 (AIPM) Member of "Project ECHO" Chronic Pain & Opioids St. Joseph’s Care Group and The Ottawa Hospital

Member of the Chronic Pain Quality Standard Advisory Committee - Health Quality Ontario

ECHO CHRONIC PAIN, Queen’s & University Health Network

Nov 8, 2018

Disclosures for Julie Besse RD

Relationships with For-Profit organizations: NONE

Relationship with Non-Profit organizations: • Paid Employee of St. Joseph’s Care Group

• Registered Dietitian (CDO) for Chronic Pain & Mental Health Programs

• Member of "Project ECHO" Chronic Pain & Opioids St. Joseph’s Care Group and The Ottawa Hospital– volunteering my expertise

• Member of the Chronic Pain Quality Standard Advisory Committee - Health Quality Ontario – volunteering my expertise

Learning Objectives

1) Provide a QUICK overview of some nutritional mechanisms associated with chronic pain

2) Help identify key nutrients involved in optimizing the management of chronic pain

Note that most of the concepts explored today are hypothetical or theorical

Nutrition and Human Health

REF: “Foods, Nutrients, and Dietary Patterns: Interconnections and Implications for Dietary Guidelines.” Tapsell LC, Neale EP, Satija A, Hu FB., Adv Nutr. May 2016 AND “The joint WHO/FAO expert consultation on diet, nutrition and the prevention of chronic diseases: process, product and policy implications., Nishida C, Uauy R, Kumanyika S, Shetty P., Public Health Nutr. Feb 2004

Source: ObesityCanada.ca

• Complex

• Inter-related • Anatomy

• Physiology

• Metabolic pathways

• Cell biology

• Food Chemistry

Meeting nutritional requirements reduces risks of chronic diseases

The “Western” or “SAD” – Standard American Diet

[PERCENTAGE] [PERCENT

AGE] [PERCENTAGE]

63%

U.S. FOOD CONSUMPTION - USDA 2009 AS A % OF CALORIES

PROCESSED FOOD Added Fats & Oils,

Sugars, Refined Grains

ANIMAL FOOD Meat, Dairy, Eggs, Fish, Seafood

WHOLE UNPROCESSED PLANT FOOD Vegetables, Fruits, Legumes, Nuts & Seeds, Whole Grains

PROCESSED PLANT FOODS ie: almonds in candy bars, apples in pies, spinach in quiche

NOT meeting Nutrition Needs

ONLY 30% of Canadians eat fruits/vegetables daily 5 or more

times daily (Statistics Canada 2016)

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Nutrition and Chronic Pain Mechanisms

REF: “Total Western Diet Alters Mechanical and Thermal Sensitivity and Prolongs Hypersensitivity Following Complete Freund's Adjuvant in Mice”., Totsch SK et al., J Pain. Jan 2016 Jan

• Poor diet quality leads to pain in mice

Per Dr. Bonakdar, Pain specialist • Inflammation • Shift of gut microbiome • Modulation of the immune System • Improvement of joint function • Elimination of pain triggers • Correct deficiencies

REF: “Prevention of Atherosclerosis by Berries: The Case of Blueberries”, Wu X, Wang TTY, Prior RL, Pehrsson PR., J Agric Food Chem. Sep 2018

Theorical Food Pyramid Model to Manage Pain

REF: “Food pyramid for subjects with chronic pain: foods and dietary

constituents as anti-inflammatory and antioxidant agents”., Rondanelli M

et al., Nutr Res Rev. June 2018

DAILY

• Fruits/vegetables, 5 portions • Carbohydraties with low glycemic index, 3 portions • Extra Virgin Olive oil • RED wine 125mL • Yogurt 125ml • Spices (Curcumin, Ginger, Echinacea) • Seeds or Nuts WEEKLY • Legumes and Fish, 4 portions • Poultry, eggs and fresh cheese, 2 portions • Red or processed meat, 1 portions • Sweets occasionally (*100g of sweets weekly) SUPPLEMENTS (top of pyramid) • Vitamin B12, Omega-3 fatty acids, Vitamin D, fibre

New Evidence for Nutrition and Chronic Pain • Systematic Review Meta-Analysis Oct 2018:

• Nutrition Intervention significant effect in ↓ pain

• Many diet strategies, many types of pain

• Target more healthful eating pattern

• 2nd Ed. SIMPAR “Feed your Destiny” Aug 2018 • A balanced & personalized nutritional regimen

• Synergic strategy that can improve management of chronic pain

REF: “A systematic review and meta-analysis of nutrition interventions for chronic noncancer pain”., Brain K, Burrows TL, Rollo ME, Chai LK, Clarke ED, Hayes C, Hodson FJ, Collins CE., J Hum Nutr Diet. 2018 Oct 7 AND “2nd edition of SIMPAR's "Feed Your Destiny" workshop: the role of lifestyle in improving pain management”., De Gregori M et al., J Pain Res. 2018 Aug 27;11:1627-1636

Canada’s Food Guide, Mediterranean or DASH DASH:

• 27% calories from fat

• 6% saturate

MEDITERRANEAN

• 35% calories from fat

• ≤ 10% saturates

• Emphasis on EVOO & oily fish

CANADA’s FOOD GUIDE

• 10% Sat, 10% Poly, 10% Mono

• Emphasis on Canola, Olive or Soybean Oil

• 2 portions fatty fish/week

USDA

• 20-35% of calories from fat

• <10% sat fats

Key Nutrition Issues associated with Chronic Pain

• Westernized “inflammatory” diet

• Vitamin D

• Fish oils and Omega-3 EPA & DHA

• Magnesium

• Fibers, FODMAP and Probiotics

• Vitamin B-complex + B12 & Folate

• Other rare but important micronutrient deficiencies • associated with westernized diet

• associated with absorption/modulation deficits (gene mutations)

ADAPTED FROM: “Evidence-Based Nonpharmacologic Strategies for Comprehensive Pain Care: The Consortium Pain Task Force White Paper., Tick H et al., Pain Task Force of the Academic Consortium for Integrative Medicine and Health., Explore (NY). 2018 May - Jun;14(3):177-211. AND Nutritional Interventions in Clinical Depression, Kaitlyn Rechenberg, Clinical Psychological Science 2016, Vol 4 (1) 144-162 Nutritional Supplements in Depressive Disorders, Monica Martinez-Cengotitabengoa and Ana Gonzalez-Pinto, Actas Esp Psiquiatr 2017; 45 (Suppl. 1): 8-15

Anti-Inflammatory/Anti-Oxidants SOURCE: https://www.jamieoliver.com/news-and-features/features/fruit-eat-the-rainbow/

REF: Health Canada - Social determinants of health and health inequalities (www.canada.ca) AND Healthy dietary habits in relation to social determinants and lifestyle factors., Johansson L et al., Br J Nutr. 1999 Mar;81(3):211-20. AND “Anti-inflammatory Diets.”, Sears B., J Am Coll Nutr. 2015;34 Suppl 1:14-21.

Goal: 7-10 fruit/veg a day RICH IN : phenolics, flavonoids, carotenoids, vitamin C, folate, pro-vitamin A, potassium, calcium, and magnesium, and pre-biotic fibers

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Anti-Inflammatory - Mediterranean Diet

Adapted from teachings by Dr. Rupinder Dhaliwal – SEE www.metabolicsyndromecanada.ca/change-program

Dietary Inflammation Index (DDII®)

REF: “Dietary Inflammatory Index and Biomarkers of Lipoprotein Metabolism, Inflammation and Glucose Homeostasis in Adults.”, Phillips CM, Shivappa N, Hébert JR, Perry IJ., Nutrients. Aug 2018

TOP 10 BEST – Foods rich in the following:

Tumeric (curcumin)

Isoflavones

Beta Carotene

Green & Black Tea

Magnesium

Ginger

Vitamin D

Omega-3 Fatty Acids

Vitamin C

Garlic & Onion family

Vitamin D may constitute a safe, simple and potentially beneficial way to reduce pain among patients with vitamin D deficiency (Helde-Franklin M.,“Vitamin D in Pain Management”, Int J Mol Sci. Oct 2017

RISK FACTORS (Medscape)

• Living in Northern Hemisphere • Sunscreen use & Less sun exposure • Darker skin • Older age • Gastro-intestinal dysfunctions • Less milk drinking • No vitamin D supplement use

VITAMIN D: Do you drink milk/substitute? Note that ONLY “liquid Milk to Drink” has to be

enriched with vitamin D BY LAW.

Do you eat 2-3 portions of FATTY FISH per week? PLANT FORM ANIMAL FORM THAT HUMANS CAN USE

3 TYPES of OMEGA-3

ALA (plant) EPA (animal form) DHA (animal form)

Only 5-15% of ALA is

transformed in EPA & DHA

Omega-3 combats Inflammatory Omega-6

• EPA fight against Ω-6 AA (arachidonic acid)

• Ω-6 are PRO-inflammatory and are omnipresent in our diet

• Ω-6:Ω-3 ratio is high in Western diet ~25:1

• Health Goal ratio: 4 :1 • Inflammatory Diseases: Goal

ratio: 1:1 • Nerve cells Integrity

Omega-3 and Chronic Pain

• Analgesia enhancement and prevention of tolerance to morphine: beneficial effects of combined therapy with omega-3 fatty acids. (Escudero GE, et al., J Pharm Pharmacol. Sep 2015)

• Ω-3 ↓inflammation & pain associated with Rheumatic Arthritis (Abdulrazaq M et

al, Nutrition Jul 2017 AND Gioxari A et al, Nutrition Jan 2018) and↓ need for NSAIDs (Lee YH et al, Arch Med Res, Jul 2012)

• ↓ pain 2° nerve injury (Galán-Arriero I et al, Biochim Biophys Acta Biomembr, Sep 2017)

• ↓ post-op pain & CRP levels (Ruiz-Tovar J et al., Clin Nutr, Jul 2018)

• Ω-3 beneficial for DB Neuropathy (Yorek MA, Curr Diabetes Rev. 2018;14(4)

• Effects similar to antidepressants & recommended adjunct treatment (“Nutritional Interventions in Clinical Depression”, K. Rechenberg, Clinical Psychological Science 2016, Vol 4 (1) 144-162 AND “Nutritional Supplements in Depressive Disorders”, M. Martinez-Cengotitabengoa & Ana Gonzalez-Pinto, Actas Esp Psiquiatr 2017)

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Do you eat Nuts, Legumes and Seeds?

• Magnesium deficiency is associated with neurological disorders such as chronic pain and migraines (“The Role of Magnesium in Neurological Disorder”, Kirkland et al, Nutrients, June 2018)

• Most common deficiency in N-America

• No tests for Magnesium body stores = identify ↓Mg with diet assessment

• Stress and alcohol intake can decrease magnesium body stores.

• Excessive supplementation of Mg causes cramps & diarrheas (separate in 3 smaller doses/d) SOURCE: https://www.123rf.com/photo

Source of Magnesium, Vitamin E, Zinc, Prebiotics, Isoflavones, Vitamin B, Fibers, etc…

Magnesium Magnesium as a NMDA Receptor blocker • Effects similar to tricyclics

antidepressants • Mg helps opioids be more

effective for lesser doses • Infusion for Migraines in ER • Glutamate-Gaba pathway • N-methyl-D-aspartate

(NMDA) receptor antagonist or blocker

• Results in its analgesic effect

REF: “Magnesium in pain research: state of the art.” Srebro D et al, Curr Med Chem. Dec 2016 “Nutritional Interventions in Clinical Depression”, K. Rechenberg, Clinical Psychological Science 2016, Vol 4 (1) 144-162 “Nutritional Supplements in Depressive Disorders”, M. Martinez-Cengotitabengoa & Ana Gonzalez-Pinto, Actas Esp Psiquiatr 2017; “Magnesium enhances opioid-induced analgesia - What we have learnt in the past decades?”, Bujalska-Zadrożny M et al, Eur J Pharm Sci. Mar 2017

REF: “Magnesium L-threonate prevents and restores memory deficits associated with neuropathic pain by inhibition of TNF-α.”, Wang J, et al., Pain Physician. 2013 Sep-Oct

Magnesium and Pain - N-Methyl-D-Aspartate Receptor blocker

• Magnesium L-threonate prevents and restores memory deficits associated with neuropathic pain by inhibition of TNF-α

• Odds of migraine ↑ 35.3X when serum magnesium was below normal

• In migraines, a low serum Mg was found to ↑CRP

• Doses of 600 mg/day of trimagnesium dicitrate for adults or 3 mg/kg/day of magnesium oxide three times a day for children and adolescents were found to be effective in preventing migraines Evidence C, Practice-based Evidence in Nutrition®Aug2017

“Serum concentration of magnesium as an independent risk factor in migraine attacks: a matched case-control study and review of the literature.”, Assarzadegan F et al, Int Clin Psychopharmacol. 2016 Sep

Gut Microbiota & Gut-Brain Axis

REF: Stress & the gut-brain axis: Regulation by the microbiome - Jane A. Foster et al., Neurobiol Stress. 2017 Dec; 7: 124–136.

ROLE OR GUT MICROBIOTA

• Energy Production

• Synthesis of Vitamins & Short Chain Fatty Acids • Modulates absorption

• Fermentation of non-digestible substances

PROTECTION

• Antimicrobial effect

• Physical barrier against pathogenic bacteria • Stimulation of immune System

MENTAL HEALTH

• Synthesis of neurotransmitters

Active Culture

=

PRO-Biotics

Abnormalties in Gut Flora results: • Decrease in BDNF • Hypo-active NMDAr • Causes GI tract inflammation • Changes Tryptophan & Kynurenine • Alters brain Serotonin Levels and

other neurotransmitters release • Changes in Isovaleric Acid • Decreased Butyric Acid

Diet & Dysbiosis (Abnormalities of the Gut Microbiome)

Diet (Fibers as Prebiotics) is one of the most important modifying factors

of the microbiota-gut-brain axis

REF “The role of microbiota in the pathogenesis of schizophrenia and major depressive disorder and the possibility of targeting microbiota as a treatment option”, Lv F et al., Oncotarget. Sep 2017

Dietary Fibers =

PRE-biotics

Microbiome and Chronic Pain

REF: “Visceral pain: gut microbiota, a new hope?” Matteo M Pusceddu et al., J Biomed Sci. 2018; 25: 73. E-pub 2018 Oct 11 AND “Stress and the Microbiota-Gut-Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome.”, Moloney RD et al, CNS Neurosci Ther. Feb 2016 AND “Nutrition, Oxidative Stress and Intestinal Dysbiosis: Influence of diet on gut microbiota in inflammatory bowel diseases”,Tomasello G et al, Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. Dec 2016

The gut microbiota dramatically impacts normal visceral pain sensation and affects the mechanisms mediating visceral nociception(Moloney RD et al, Feb 2016)

• GERD, Gastroparesis and Gastric Ulcers

• Pancreatic Pain

• Chronic Prostatitis • Chronic Pelvic Pain

• Irritable Bowel Disease

• Food Allergies and Intolerances & MCAS

• Inflammatory Bowel Diseases

• Constipation and Ehlers-Danlos Syndrome

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Vitamin B-12 deficiency symptoms Deficiency causes neurological disorders (irreversible sometimes) including pain

REF: UptoDate

REF: “Evidence-Based Nonpharmacologic Strategies for Comprehensive Pain Care: The Consortium Pain Task Force White Paper”., Tick H et al., Pain Task Force of the Academic Consortium for Integrative Medicine and Health., Explore (NY). 2018 May - Jun;14(3):177-211.

Vitamin B-12 Deficiency Symptoms

• Subtle neurologic, cognitive, or psychiatric changes

• Depression or mood impairment

• Irritability

• Insomnia

• Cognitive slowing

• Fatigue, Forgetfulness

• Psychosis, Dementia

• Poor appetite

• Visual disturbances (ass w/optic atrophy)

• Tongue: glossitis - red beefy color

• Peripheral sensory deficits

• Weakness, which may progress to paraplegia and incontinence if severe

• Impaired position sense

• Impaired vibration sense

• Lhermitte sign, a shock-like sensation that radiates to the feet during neck flexion

• Ataxia or positive Romberg test

• Abnormal deep tendon reflexes

• Extrapyramidal signs (eg, dystonia, dysarthria, rigidity)

• Restless legs syndrome

SEE ALSO “Challenging clinical presentations of pernicious anemia”., Oo TH et al, Discov Med. Sep 2017

Vitamin B12 & Vitamin B9 (Folate) testing • 80% cases are missed with CBC only…

• B12 deficiency can hide Folate deficiency & vice versa

• Combined anemias hide each-other (microcytic +macrocytic)

• Ferritin levels falsely normalized by ↑inflammation

• Blood serum levels ≠ body tissues levels. B12 below 300pmol/L is “borderline”, Ideal levels for mental health is >450pmol/L(Kimball SM, Mirhosseini N, Rucklidge J. Nutrients. 2018 Jan 30 ;10(2))

• ++ genetic mutation of enzymes transporting B12 and Folate (& other B-vitamins) through Blood Brain Barrier; MTHFR…

• B12 needs folate, and Folates need B12 (with B6 and B2) in the One-Carbon Methylation Pathway

• Elevated Homocysteine can indicate B12 or Folate problems, but 70$ charged to the patient

OTHER REF: “Megaloblastic Anemias: Nutritional and Other Causes”., Green R, Datta Mitra A., Med Clin North Am. Mar 2017.; “Anemias beyond B12 and iron deficiency: the buzz about other B's, elementary, and nonelementary problems”. Green R., Hematology Am Soc Hematol Educ Program. 2012.; “Vitamin B12 deficiency from the perspective of a practicing hematologist”., Green R., Blood. May 2017; [Treatable Dementia due to Vitamin B12 and Folate Deficiency]. Yoshizawa T., Brain Nerve. Apr 2016; “Vitamin B12”., Smith AD, Warren MJ, Refsum H., Adv Food Nutr Res. 2018;83:215-279

• B-12 - Yellow Arrow

• B-9 Folate – Green Wheel

• B-2 Riboflavin - Green Arrow

• B-6 Pyridoxine - Blue Arrow

“Anti-depressants such as SSRIs seems to have an effect on most of chronic pain conditions”

B-Complex Vitamins and Methylation Pathway

REF: “Nutritional Interventions in Clinical Depression”, K. Rechenberg, Clinical Psychological Science 2016, Vol 4 (1) 144-162

“Nutritional Supplements in Depressive Disorders”, M. Martinez-Cengotitabengoa & Ana Gonzalez-Pinto, Actas Esp Psiquiatr 2017

“Chronic Pain and Mental Health Disorders: Shared Neural Mechanisms, Epidemiology, and Treatment”, Hooten WM. Mayo Clin Proc. Jul 2016

“Treating Chronic Pain with SSRIs: What Do We Know?”, Patetsos E, Horjales-Araujo E., Pain Res Manag. 2016

Vitamin B12 and Methylcobalamin Folate and Methyltetrahydrofolate (Levomefolate)

• Methylcobalamin has potential analgesic effects in many neurological conditions

• In rat studies, supplementing methylcobalamin attenuated neuropathic pain

• Methyltetrahydrofolate at 7.5-15mg helps in management of depression (1mg avail. in Canada) REF: “Methylcobalamin: a potential vitamin of pain killer”, Zhang M, Han W, Hu S, Xu H.Neural Plast. 2013;2013:424651

“Methylcobalamin ameliorates neuropathic pain induced by vincristin in rats: Effect on loss of peripheral nerve fibers and imbalance of cytokines in the spinal dorsal horn.”, Xu J, Wang W, Zhong XX, Feng Y, Wei X, Liu XG.,Mol Pain. Jun 2016

“Adolescence/adult onset MTHFR deficiency may manifest as isolated and treatable distinct neuro-psychiatric syndromes”., Gales A et al., Orphanet J Rare Dis. 2018 Feb 1;13(1):29

“What You Need to Know About the MTHFR Gene” Ashley Marcin reviewed by Karen Gill, MD, July 13, 2018 www.healthline.com

“Folate, folic acid and 5-methyltetrahydrofolate are not the same thing”., Scaglione F, Panzavolta G., Xenobiotica. May 2014

SOME SUGGESTED MECHANISMS

• Intra-epidermal nerve fibers

• Mitochondria

• Inflammatory cytokines

• Folate Methylation Pathway

• Enzymatic function

• Spinal Dorsal Horn

• “Epigenetic modifications are influenced by … environmental factors, including dietary exposures and nutritional status.” (“Emerging concepts on the role of epigenetics in the relationships between nutrition and health”, Stover PJ et al. 2018)

• DNA Methyl Group = Epigenetic Tag (Folate, Vitamin B2, B6, B12, Methionine, Betaine, Choline)

epigenetic tags

SOURCE: C. Haughton

Epigenetics and Nutrigenomics

SEE ALSO: “Regulation of gene expression and pain states by epigenetic mechanisms.”, Géranton SM, Tochiki KK., Prog Mol Biol Transl Sci. 2015; “Folate and epigenetics: why we should not forget bacterial biosynthesis”., Kok DE et al, Epigenomics. Sep 2018

Epigenetics Chronic Pain “The persistent nature of pain (somatic, visceral, or neuropathic) suggests that epigenetic machinery may be a critical factor driving chronic pain.” (“Targeting Epigenetics Mechanisms for Chronic Pain” Ligon CO et al. 2016)

SOURCE: Dr. Bonakdar Eudcation Slides SEE ALSO: “Chronic postsurgical pain: is there a possible genetic link?”, James SK., Br J Pain. 2017 Nov “Recent advances in understanding neuropathic pain: glia, sex differences, and epigenetics”., Machelska H et al, F1000Res. Nov 2016; “Chronic pain: emerging evidence for the involvement of epigenetics”., Denk F, McMahon SB., Neuron. Feb 2012

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Latent Scurvy with pain & other non-specific symptoms (Vitamin-C Deficiency) 3 cases of previously healthy children

• no significant medical history: all had microcytic anemia

• leg pain and refusal to walk

• 2 with gingival hyperplasia & petechia, ↓vit D, one with night sweats and gingival bleeding for past few weeks

3 cases of alcoholics

• alcoholics

• extreme lassitude

• leg pain

• 2 with discreet classic symptoms (petechiae or hyperkeratosis of the legs)

REF: “Scurvy: still a threat in the well-fed first world?” Ceglie G et al., Arch Dis Child.Aug 2018

REF: “Latent Scurvy with tiredness and leg pain in alcoholics”, Christine Lux-Battistelli et al, Medicine (Baltimore) Nov2017

Vitamin D

EPA/DHA Omega-3

Vitamin C, A (Beta-Carotene), B-Vitamins, Flavonoids, Prebiotics

Magnesium, Zinc, Vitamin E, Isoflavones, Prebiotics

Vitamin B12

B- vitamins, Prebiotics

In conclusion… HEALTHY DIET for PAIN MANAGEMENT

• Liquid Milk ≥2 cups/d

• ≥ 2-3 portions fatty fish/wk

• ≥ 7 portions fruits/vegetables/d .

• Plant proteins (legumes, nuts, seeds)

• Animal foods

• Whole grains/complex carbohydrates

Adapted from : Tatiana Ayazo /rd.com

125mL

Vegetables:

Allium

Cruciferous

Tomato/Peppers

Orange colored

Green leafy

Citrus, Berries

Orange colored

Black or

Green tea,

70%+ Cocoa

125mL Red wine

Herbs & Spices

“See-Food Diet” (Diet Infographics)