nutritional supplementation in pain management: clinical strategies nancy cotter md medical director...
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Nutritional Supplementation in Pain Management: Clinical
Strategies
Nancy Cotter MDMedical Director
Atlantic Integrative MedicineMorristown Memorial and Overlook Hospitals
Morristown and Summit NJ
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Nutraceuticals and pain management
Highlight the use of nutritional supplementation in the context of a holistic approach to pain managementDiscuss evidence based use of nutraceuticals for pain management, site of action, practical aspects of useAnalyze the anti-inflammatory and anti-pain benefits of omega-3 and omega-6 fatty acids, glucosamine sulfate, and other nutrients.Consider nutritional supplementation for patients with pain.
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Functional approach to pain management
Assess substrate: state of tissue, circulation, nervous systemExamine structure: musculoskeletal and organ restrictions Evaluate Function:
Physiologic: adequate nutrients and intact biological pathways for proper physiologic functioningMental/ emotional: mind/ spirit axis
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Functional approach to pain management
Physical pain may be the final common pathway of single or multiple levels of dysfunction: biological emotional
spiritual
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Functional approach to pain management:1. Evaluate inflammatory load, oxidative status, food sensitivities,
health of GI function, levels of key nutrients
2. Decrease inflammatory load through diet
3. Detoxify as necessary by removing aggravating conditions and by upregulation of detoxification pathways
4. Add anti- inflammatory nutraceuticals and intervene at as many sites as possible
5. Modify aggravating structural imbalances: tight muscles, tendons and joint capsules, postural defects, muscle weaknesses
6. Restore energy movement and balance
7. Implement mental/ emotional habits to maintain outlook,
maintain good habits, prevent stress- related aggravation of condition
This is a baseline approach to chronic inflammation- based pain: Rheumatoid and Osteoarthritis, Fibromyalgia, chronic muscular pain, neurodegenerative pain, peripheral vascular pain
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OsteoarthritisMyofascial Pain
FibromyalgiaNeurodegenerative painPeripheral Vascular Pain
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Pain and the anti- inflammatory
approachInflammatory mediators are also pain mediators: IL2, MCF, TNF, therefore……
Decreasing inflammatory load decreases pain
Anti- inflammatory Diet: Eliminate foods that are pro- inflammatory
Improve overall nutritional status: reduce oxidatve stress to increase tissue responsiveness to natural supplements or other interventions
Exercise and weight loss: Increase lean muscle mass: adipose tissue produces adipokines which likely contribute to joint inflammation separately and distinctly from mechanical stress
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Supplementation for Pain Management
1.Modify Cell membrane composition via anti- inflammatory diet and omega-3 supplementation
2. Use supplements that dampen the inflammatory cascade
3. Use supplements that modify structure and disease course if possible
4. Support biological matrix with vitamins, minerals, cofactors
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oOmega-6: Linoleic acid (LA)--vegetable oils, seeds, nuts
oArachidonic Acid (AA)--meat and dairy products
o Gamma Linolenic Acid (GLA)--borage and primrose oil
o Omega-3: Alpha Linolenic Acid (ALA)--legumes, leafy vegetables, flax, flaxseed and canola oils
oEicosopentaenoic acid (EPA)-fish oil
oDocosahexaenoic acid (DHA)--fish oil, breast milk
Essential Fatty Acids:
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Omega 6 Fatty Acid (Linoleic Acid)
Omega 3 Fatty Acids(alpha-linolenic acid)
Gamma-linolenic acid(GLA)
Arachidonic Acid
LeukotrienesProstaglandins (PGE2)
(Inflammatory)
Lipoxygenase
Cyclo-oxygenase
(COX)
Eicosatetraenoic Acid
ProstaglandinsPGE1, PGE3 5-Leukotrienes
Docosahexaenoic acid(DHA)
Cyclooxygenase(COX )
Elongase
Dihomogammalinoleic acid (DGLA)
Stearidonic acid
Elongase
Δ6-Desaturase
Δ5-Desaturase
Δ6-Desaturase
Eicosapentaenoic Acid
Lipoxygenase(LOX)
Elongase, Δ4-Desaturase
Δ5-Desaturase
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Omega 3 Fatty AcidsStandard American Diet 40:1 to 10:1 n=6 to n=3 Omega FA4:1 adequate for healthy individuals1:1 preferred in inflammatory conditions for treatment
Covington M Am Fam Phys 2004; 70:133-40
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ω3 Fatty Acid sources: marine
Fish oils: Mackerel, herring, salmon, bluefin tuna, sardinesAll fish have ω3 LCFA; some more concentrated than othersFlax seed oil for vegetarians: high volumes necessary for EPA production
(approx 11:1 ratio); DHA now available from algae
Simopoulos AP. Essential fatty acids in health and chronic
diseases Forum of Nutrition. 2003;56:67-70
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Sources of Fish OilFish
Contamination with PCB, dioxin, and HgHigher in AA than fish oil
Crude fish oilHigh contamination
Health food gradeMinimal contamination with PCB’s and dioxins
Ultra-Refined EPA/DHA ConcentratesRemoval of PCB’s and other toxinsCan be used in high doses
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ω3 Fatty Acid sources: vegetarian
Flax seed oil for vegetarians: high volumes necessary for EPA production (approx 11:1 conversion ratio ALA: EPA)
1 tbsp flax oil contains approx 7g ALA(www.pbi.nrc.ca/en/bulletin/2002issue2/page5.htm)
Other plant sources: purslane, walnuts, canola
Simopoulos AP. Essential fatty acids in health and chronic
diseases Forum of Nutrition. 2003;56:67-70
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o Standard American Diet 40:1 to 10:1
o Maintenance 2.5 g/d of EPA/ DHA
o Strive for Omega 6: Omega-3 ratio of 4:1
o Healing phase 1:1
o Pain management/ treatment chronic pain up to 7.5 g/d
Cleland LG. James MJ. Proudman SM. The role of fish oils in the treatment of rheumatoid arthritis. Drugs. 2003;63(9):845-53
Recommended intake Omega-3 fats:
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Omega 6 Fatty Acid (Linoleic Acid)
Omega 3 Fatty Acids(alpha-linolenic acid)
Gamma-linolenic acid(GLA)
Arachidonic Acid
LeukotrienesProstaglandins (PGE2)
(Inflammatory)
Lipoxygenase
Cyclo-oxygenase
(COX)
Eicosatetraenoic Acid
ProstaglandinsPGE1, PGE3 5-Leukotrienes
Docosahexaenoic acid(DHA)
Cyclooxygenase(COX )
Elongase
Dihomogammalinoleic acid (DGLA)
Stearidonic acid
Elongase
Δ6-Desaturase
Δ5-Desaturase
Δ6-Desaturase
Eicosapentaenoic Acid
Lipoxygenase(LOX)
Elongase, Δ4-Desaturase
Δ5-Desaturase
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Omega 6 Fatty Acid (Linoleic Acid)
Omega 3 Fatty Acids(alpha-linolenic acid)
Gamma-linolenic acid(GLA)
Evening Primrose OilBorage Oil/ Black Current Oil
Arachidonic Acid
LeukotrienesProstaglandins (PGE2)
(Inflammatory)
Eicosapentaenoic Acid(EPA)
ProstaglandinsPGE1, PGE3
5-Leukotrienes(less inflammatory)
Docosahexaenoic acid(DHA)
Cyclooxygenase(COX )
Δ5-Desaturase
Dihomogammalinoleic acid (DGLA)
Eicosatetraenoic acidElongase
Δ6-Desaturase
Elongase
Δ6-Desaturase
Lipoxegenase (LOX)
Cyclo-oxygenase
(COX) Lipoxygenase
Desaturase is suppressed by excessive intake of saturated, trans fat, insulin excess; requires Mg, Zn*
Free radical peroxidation of AA = isoprostanes (stronger inflamm effect)
*Wallace JM. Nutritional and botanical modulation of the inflammatory cascade Integrative Cancer Therapies, 2002. 1(1):7-37
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Arachidonic Acid
Phospholipase A-2
Cyclo-oxygenase
PathwayLipoxygenase
Pathway
Prostaglandins&
ThromboxanesLeukotrienes
SteroidsAspirin
NSAIDs
COX II Inhibitors:
Celebrex, Vioxx, Mobic
Colchicine
Sulfasalazine
Leukotriene Inhibitors:
Accolate, Singulair, Zyflo
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Supplementation:
Inflammatory profile modificationStructural modificationMatrix Support
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BoswelliaSignificant improvement over placebo for osteoarthritis of the knee
Kimmatkar N. Thawani V. Hingorani L. Khiyani R. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial. Phytomedicine. 10(1):3-7, 2003
Ammon HP. Boswellic acids in chronic inflammatory diseases. [Review] [69 refs] [Journal Article. Review] Planta Medica. 72(12):1100-16, 2006
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BoswelliaPotentiates effects of glucosamine in experimental conditionsSingh et al Bioorganic and Medicinal Chemistry Letters 17 (2007) 3706-3711
Blocks arachidonic acid - to - leukotriene conversionPoeckel D. Werz O. Boswellic acids: biological actions and molecular targets. Current Medicinal Chemistry. 13(28):3359-69, 2006
Standardized to 65% boswellic acids; 300 mg tid
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BromelainSulfur containing enzyme from pineapple plantInhibits PGE2 synthesisEnhances PGE1 synthesisDecreases vascular permeabilitySeparate analgesic propertiesEffective Dosage in studies ranges between 100-900+ mg/dayNo significant adverse effects
Brien,S, Lewith, Walker A et al 2004 Evidence based Complementary and Alternat Med(3) :251-257
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GingerGinger extract reduced inflammation in synovial cell culturesFrondoza CG. et al In Vitro Cellular & Developmental Biology. 40(3-4):95-101, 2004
Ginger Inhibits COX and LOX pathwaysGrzanna et al J Med Food 2005
8(2)125-132Ginger ass’d w/ weakened delayed -type hypersensitivity in mice
Zhou et al J Ethnopharm 2006 105:101-105
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Curcumin
Singh S. Khar A.Current Medicinal Chemistry - Anti-Cancer Agents. 6(3):259-70, 2006
Bright JJ. Curcumin and autoimmune disease. Advances in Experimental Medicine & Biology. 595:425-51, 2007. Shishodia S. Sethi G. Aggarwal BB. Curcumin: getting back to the roots. Annals of the New York Academy of Sciences. 1056:206-17, 2005 Nov.
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Harpagophytum procumbens: Devil’s Claw
Harpagophytum and low back painN= 130 treated with H procumbens ; significant improvement with no serious side effectsLaudahn D Walper A 2001 Phytother Res (15)621-624
Likely acts synergistically with NSAIDsBrendler T et al J Herb Pharmacotherapy 6(1): 89-126
COX2 inhibitorHuang et al J Ethnopharmacology 2006; 104:149-155
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Omega 6 Fatty Acid (Linoleic Acid)
Omega 3 Fatty Acids(alpha-linolenic acid)
Gamma-linolenic acid(GLA)
Evening Primrose OilBorage Oil/ Black Current Oil
Arachidonic Acid
LeukotrienesProstaglandins (PGE2)
(Inflammatory)
Lipoxygenase
Cyclo-oxygenase
(COX)
Eicosapentaenoic Acid(EPA)
ProstaglandinsPGE1, PGE3
5-Leukotrienes(less inflammatory)
Lipoxygenase(LOX)
Docosahexaenoic acid(DHA)
Cyclooxygenase(COX )
Δ5-Desaturase
Dihomogammalinoleic acid (DGLA)
Eicosatetraenoic acidElongase
Δ6-Desaturase
Elongase
Δ6-Desaturase
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Arachidonic Acid
Phospholipase A-2
Cyclo-oxygenase
Pathway
Lipoxygenase
Pathway
Prostaglandins&
ThromboxanesLeukotrienes
SteroidsAspirin
NSAIDsCOX II Inhibitors:
Celebrex, Vioxx, Mobic
ColchicineSulfasalazineLeukotriene Inhibitors:
Accolate, Singulair, Zyflo
Curcumin, Bromelain
Ginger, Devils ClawBoswellia
Turmeric
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Horse Chestnut
Treatment of patients with venous insufficiency with fresh plant horse chestnut seed extract: a review of 5 clinical studies.
Suter A. Bommer S. Rechner J. Advances in Therapy. 23(1):179-90, 2006 Horse chestnut seed extract for chronic venous insufficiency
Pittler MH. Ernst E. Cochrane Database of Systematic Reviews. (1):CD003230, 2006
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White Willow Bark
Tanacetum parthenium and Salix alba (Mig-RL) combination in migraine prophylaxis: a prospective, open-label study.
Shrivastava R. Pechadre JC. John GW. Clinical Drug
Investigation. 26(5):287-96, 2006 Herbal medicine for low back pain.Gagnier JJ. van Tulder M. Berman B. Bombardier C. Cochrane
Database of Systematic Reviews. (2):CD004504, 2006
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α-Lipoic Acid (A-LA)
ALADIN Trial :alpha-lipoic 600 mg/day IV over 3 weeks At 19 days, improvement in total symptom score of at least
30%, were 70.8% in ALA 1200, 82.5% in ALA 600, 65.2% in ALA 100, and 57.6% in PLAC (ALA 600 vs PLAC; p = 0.002)
Ziegler D. Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical reviewTreatments in Endocrinology. 3(3):173-89, 2004 Veresiu IA. Treatment of diabetic polyneuropathy with alpha-lipoic acid is evidence based. Romanian Journal of Internal Medicine. 42(2):293-9, 2004
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acetyl l carnitine
Acetyl-L-carnitine in neuropathic pain: experimental data.
Chiechio S. et al CNS Drugs 2007 21 Suppl 1:31-8
Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients.
Rossini M. et al Clinical & Experimental Rheumatology. 25(2):182-8, 2007
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St John’s WortAnalgesic and topical anti-inflammatory activity of Hypericum canariense L. and Hypericum glandulosum Ait.
Rabanal RM. Et al Journal of Ethnopharmacology. 96(3):591-
6, 2005 Anti-inflammatory and analgesic activity of Indian Hypericum perforatum L.
Kumar V. Singh PN. Bhattacharya SK. Indian Journal of
Experimental Biology. 39(4):339-43, 2001
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Symptom Modification: Glucosamine & Chondroitin
GAIT study Clegg DO et al. NEJM 2006;354:795-808.
GUIDE study Herrero- Beaumont et al Arth Rheum 2007; 555-67
Meta- analysesTowheed TE et al Cochrane Database 2005(2):CD002946
Biggee BA et al Med Health R 2004; 87:176-179 Richy F et al Arch Intern Med 2003; 163:1514-22
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Structural Modification: Glucosamine & Chondroitin
Glucosamine sulfate 1500mg qd x 3yearsJoint space narrowing over 3 years -3.1 mm with placebo vs 0.06mm with glucosamine Five year followup RR of lower limb surgery 0.52 compared to control
Reginster Lancet 2001 357:251-56Glucosamine sulfate 1500mg qd x 3yearsJoint space narrowing over 3 years -0.19 mm with placebo vs 0.04 mm with glucosamine Five year followup 75% reduction of knee replacement surgery as compared to control
Pavelka et al. Arch Int Med 2002 162(18):2113-23
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Structural modificationS-adenosyl-L-methionine:SAMe
As effective as ibuprofenFetrow CW Avila JR Ann Pharmacotherapy 35(11)1414-25Significant improvement over placeboBradley JD et al J Rheumatol 1994; 21: 905-911
Soeken KL et al J Fam Prac 2002 51:425-430Acts as a restorative after damage induced by TNF alphaGutierrez et al 200737: 27-31
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Structural modification:Avocado/ soybean unsaponifiables
Byproduct of soapmakingNot widely available in US currentlySignificant improvement over placebo in multiple trialsErnst E: Clin Rheum 2003; 22(4-5):285-288
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Matrix Support: Vitamin D
Vitamin D Evolution and function of vitamin D. Holick MF. Recent Results in Cancer Research. 164:3-28,
2003 Heath K, Elovic E Am J Phys Med Rehab 2006 (85)916-923
Vitamin D deficiency: what a pain it is. Holick MF. Mayo Clinic Proceedings. 78(12):1457-9, 2003
Magnesium, Calcium & Zinc
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Other things to consider in context
Muscle weakness, tightness, imbalanceFascial tension and disorganizationMind- body interventions
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Route of deliveryOral
Pills and capsules Liquid extractTinctures/teasPatient preference and comfort
Topical preparationsLocal deliveryAvoid systemic effectsKeeps pills at minimum
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Combination Products
Allows intervention in multiple pathwaysSynergistic and antagonistic effects under investigationWith potentiation and synergistic activities, may need less of each single agent
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Putting it all together
Assess biochemical and tissue health before supplementationLaboratory studies:
Inflammatory load: CRP, ESROxidative stressVitamin levels if deficiency suspected: Vitamin D, B12Critical minerals: Mg, Zn
Assess diet healthAnti- inflammatory dietFat Resistance Diet by Leo Galland
Gives patients recipes and diet plan if structure is desired; guidelines for “design it yourself” approachIf weight loss is desired, begin at Stage IIf weight loss is desired, begin at Maintenance phase
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Putting it all togetherSupplementation
Consider waiting until dietary changes have been implemented
Intervene at multiple sites: reduce AA intake/modify FA supply/ COX-LOX / joint modification/ antioxidantsFish oil daily for 3- 6 months, then 5x/week Focus on combination anti- inflammatory productsMay need to try several products for a few weeks each to find best benefit/ side effect ratioMost commonly: GI discomfort; reduce by 1/3 and ramp up 1/3 dose per week; treat GI imbalance It might be useful to have a slide listing all the supplements and the dosages for convenience
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In Conclusion:1. Pain is the manifestation of multi- level imbalance2. Inflammation is the final common pathway in many
types of pain3. Multiple natural anti- inflammatory compounds
exist in nature; they are still being defined4. Using an anti- inflammatory diet improves overall
health and tissue responsiveness to interventions6. Optimal supplementation may require some trials in
materials and dosing7. Use supplements to intervene at multiple sites in
the inflammatory cascade8. Supplementation is one modality in holistic pain
management; consider it in the context of structural and mind body interventions
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