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Nutritional Supplementation in Pain Management: Clinical Strategies Nancy Cotter MD Medical Director Atlantic Integrative Medicine Morristown Memorial.

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Presentation on theme: "Nutritional Supplementation in Pain Management: Clinical Strategies Nancy Cotter MD Medical Director Atlantic Integrative Medicine Morristown Memorial."— Presentation transcript:

1 Nutritional Supplementation in Pain Management: Clinical Strategies Nancy Cotter MD Medical Director Atlantic Integrative Medicine Morristown Memorial and Overlook Hospitals Morristown and Summit NJ

2 Nutraceuticals and pain management Highlight the use of nutritional supplementation in the context of a holistic approach to pain management Discuss evidence based use of nutraceuticals for pain management, site of action, practical aspects of use Analyze 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.

3 Functional approach to pain management Assess substrate: state of tissue, circulation, nervous system Examine structure: musculoskeletal and organ restrictions Evaluate Function: Physiologic: adequate nutrients and intact biological pathways for proper physiologic functioning Mental/ emotional: mind/ spirit axis

4 Functional approach to pain management Physical pain may be the final common pathway of single or multiple levels of dysfunction: biological emotional spiritual

5 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

6 Osteoarthritis Myofascial Pain Fibromyalgia Neurodegenerative pain Peripheral Vascular Pain

7 Pain and the anti- inflammatory approach Inflammatory 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

8 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

9 o Omega-6: Linoleic acid (LA)--vegetable oils, seeds, nuts o Arachidonic 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 o Eicosopentaenoic acid (EPA)-fish oil o Docosahexaenoic acid (DHA)--fish oil, breast milk Essential Fatty Acids:

10 Omega 6 Fatty Acid (Linoleic Acid) Omega 3 Fatty Acids (alpha-linolenic acid) Gamma-linolenic acid (GLA) Arachidonic Acid Leukotrienes Prostaglandins (PGE2) (Inflammatory) Lipoxygenase Cyclo-oxygenase (COX) Eicosatetraenoic Acid Prostaglandins PGE1, 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

11 Omega 3 Fatty Acids Standard American Diet 40:1 to 10:1 n=6 to n=3 Omega FA 4:1 adequate for healthy individuals 1:1 preferred in inflammatory conditions for treatment Covington M Am Fam Phys 2004; 70:133-40

12 ω3 Fatty Acid sources: marine Fish oils: Mackerel, herring, salmon, bluefin tuna, sardines All fish have ω3 LCFA; some more concentrated than others Flax 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

13 Sources of Fish Oil Fish Contamination with PCB, dioxin, and Hg Higher in AA than fish oil Crude fish oil High contamination Health food grade Minimal contamination with PCBs and dioxins Ultra-Refined EPA/DHA Concentrates Removal of PCBs and other toxins Can be used in high doses

14 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

15 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): Recommended intake Omega-3 fats:

16 Omega 6 Fatty Acid (Linoleic Acid) Omega 3 Fatty Acids (alpha-linolenic acid) Gamma-linolenic acid (GLA) Arachidonic Acid Leukotrienes Prostaglandins (PGE2) (Inflammatory) Lipoxygenase Cyclo-oxygenase (COX) Eicosatetraenoic Acid Prostaglandins PGE1, 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

17 Omega 6 Fatty Acid (Linoleic Acid) Omega 3 Fatty Acids (alpha-linolenic acid) Gamma-linolenic acid (GLA) Evening Primrose Oil Borage Oil/ Black Current Oil Arachidonic Acid Leukotrienes Prostaglandins (PGE2) (Inflammatory) Eicosapentaenoic Acid (EPA) Prostaglandins PGE1, PGE3 5-Leukotrienes (less inflammatory) Docosahexaenoic acid (DHA) Cyclooxygenase (COX ) Δ5-Desaturase Dihomogammalinoleic acid (DGLA) Eicosatetraenoic acid Elongase 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, (1):7-37

18 Arachidonic Acid Phospholipase A-2 Cyclo-oxygenase Pathway Lipoxygenase Pathway Prostaglandins & Thromboxanes Leukotrienes Steroids Aspirin NSAIDs COX II Inhibitors: Celebrex, Vioxx, Mobic Colchicine Sulfasalazine Leukotriene Inhibitors: Accolate, Singulair, Zyflo

19 Supplementation: Inflammatory profile modification Structural modification Matrix Support

20 Boswellia Significant 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): , 2006

21 Boswellia Potentiates effects of glucosamine in experimental conditions Singh et al Bioorganic and Medicinal Chemistry Letters 17 (2007) Blocks arachidonic acid - to - leukotriene conversion Poeckel D. Werz O. Boswellic acids: biological actions and molecular targets. Current Medicinal Chemistry. 13(28): , 2006 Standardized to 65% boswellic acids; 300 mg tid

22 Bromelain Sulfur containing enzyme from pineapple plant Inhibits PGE2 synthesis Enhances PGE1 synthesis Decreases vascular permeability Separate analgesic properties Effective Dosage in studies ranges between mg/day No significant adverse effects Brien,S, Lewith, Walker A et al 2004 Evidence based Complementary and Alternat Med(3) :

23 Ginger Ginger extract reduced inflammation in synovial cell cultures Frondoza CG. et al In Vitro Cellular & Developmental Biology. 40(3-4):95-101, 2004 Ginger Inhibits COX and LOX pathways Grzanna et al J Med Food (2) Ginger assd w/ weakened delayed -type hypersensitivity in mice Zhou et al J Ethnopharm :

24 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, 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.

25 Harpagophytum procumbens: Devils Claw Harpagophytum and low back pain N= 130 treated with H procumbens ; significant improvement with no serious side effects Laudahn D Walper A 2001 Phytother Res (15) Likely acts synergistically with NSAIDs Brendler T et al J Herb Pharmacotherapy 6(1): COX2 inhibitor Huang et al J Ethnopharmacology 2006; 104:

26 Omega 6 Fatty Acid (Linoleic Acid) Omega 3 Fatty Acids (alpha-linolenic acid) Gamma-linolenic acid (GLA) Evening Primrose Oil Borage Oil/ Black Current Oil Arachidonic Acid Leukotrienes Prostaglandins (PGE2) (Inflammatory) Lipoxygenase Cyclo-oxygenase (COX) Eicosapentaenoic Acid (EPA) Prostaglandins PGE1, PGE3 5-Leukotrienes (less inflammatory) Lipoxygenase (LOX) Docosahexaenoic acid (DHA) Cyclooxygenase (COX ) Δ5-Desaturase Dihomogammalinoleic acid (DGLA) Eicosatetraenoic acid Elongase Δ6-Desaturase Elongase Δ6-Desaturase

27 Arachidonic Acid Phospholipase A-2 Cyclo-oxygenase Pathway Lipoxygenase Pathway Prostaglandins & Thromboxanes Leukotrienes Steroids Aspirin NSAIDs COX II Inhibitors: Celebrex, Vioxx, Mobic Colchicine Sulfasalazine Leukotriene Inhibitors: Accolate, Singulair, Zyflo Curcumin, Bromelain Ginger, Devils Claw Boswellia Turmeric

28 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

29 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

30 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

31 acetyl l carnitine Acetyl-L-carnitine in neuropathic pain: experimental data. Chiechio S. et al CNS Drugs 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

32 St Johns Wort Analgesic 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

33 Symptom Modification: Glucosamine & Chondroitin GAIT study Clegg DO et al. NEJM 2006;354: GUIDE study Herrero- Beaumont et al Arth Rheum 2007; Meta- analyses Towheed TE et al Cochrane Database 2005(2):CD Biggee BA et al Med Health R 2004; 87: Richy F et al Arch Intern Med 2003; 163:

34 Structural Modification: Glucosamine & Chondroitin Glucosamine sulfate 1500mg qd x 3years Joint 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 : Glucosamine sulfate 1500mg qd x 3years Joint space narrowing over 3 years 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 (18):

35 Structural modification S-adenosyl-L-methionine:SAMe As effective as ibuprofen Fetrow CW Avila JR Ann Pharmacotherapy 35(11) Significant improvement over placebo Bradley JD et al J Rheumatol 1994; 21: Soeken KL et al J Fam Prac : Acts as a restorative after damage induced by TNF alpha Gutierrez et al : 27-31

36 Structural modification: Avocado/ soybean unsaponifiables Byproduct of soapmaking Not widely available in US currently Significant improvement over placebo in multiple trials Ernst E: Clin Rheum 2003; 22(4-5):

37 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) Vitamin D deficiency: what a pain it is. Holick MF. Mayo Clinic Proceedings. 78(12):1457-9, 2003 Magnesium, Calcium & Zinc

38 Other things to consider in context Muscle weakness, tightness, imbalance Fascial tension and disorganization Mind- body interventions

39 Route of delivery Oral Pills and capsules Liquid extract Tinctures/teas Patient preference and comfort Topical preparations Local delivery Avoid systemic effects Keeps pills at minimum

40 Combination Products Allows intervention in multiple pathways Synergistic and antagonistic effects under investigation With potentiation and synergistic activities, may need less of each single agent

41 Putting it all together Assess biochemical and tissue health before supplementation Laboratory studies: Inflammatory load: CRP, ESR Oxidative stress Vitamin levels if deficiency suspected: Vitamin D, B12 Critical minerals: Mg, Zn Assess diet health Anti- inflammatory diet Fat Resistance Diet by Leo Galland Gives patients recipes and diet plan if structure is desired; guidelines for design it yourself approach If weight loss is desired, begin at Stage I If weight loss is desired, begin at Maintenance phase

42 Putting it all together Supplementation Consider waiting until dietary changes have been implemented Intervene at multiple sites: reduce AA intake/modify FA supply/ COX-LOX / joint modification/ antioxidants Fish oil daily for 3- 6 months, then 5x/week Focus on combination anti- inflammatory products May need to try several products for a few weeks each to find best benefit/ side effect ratio Most 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

43 In Conclusion: 1. Pain is the manifestation of multi- level imbalance 2. Inflammation is the final common pathway in many types of pain 3. Multiple natural anti- inflammatory compounds exist in nature; they are still being defined 4. Using an anti- inflammatory diet improves overall health and tissue responsiveness to interventions 6. Optimal supplementation may require some trials in materials and dosing 7. Use supplements to intervene at multiple sites in the inflammatory cascade 8. Supplementation is one modality in holistic pain management; consider it in the context of structural and mind body interventions

44 THANK YOU


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