MS CENTER

1. MS CENTER ******** TO DO- 55�prof.-O�start, 15� the good, 30� antiox, 45� pascal Thanks -thanks for intro -thanks to locals Subj -Will discuss alt med and MS -controversial and confusing -important but often not discussed-like elephant in liv rm -Admirable that part of grand rounds Me -yes conv sci and clinical, BUT recognize pt interest; I got interested when pts asked questions and I realized it took me long time to come up with clear answers to questions. Talk (organiz on slide 3) Handouts- -copies of PowerPoint -handout with detailed alphabetical listing of all supplements talked about today and more -lay handout that can give to pts if time limited or interest is limited -COPYRIGHT-did because of copies on internet, feel free to make copies of lay handout Rmmsc-Info for presentation-developed through cam program at RMMSC ******** TO DO- 55�prof.-O�start, 15� the good, 30� antiox, 45� pascal Thanks -thanks for intro -thanks to locals Subj -Will discuss alt med and MS -controversial and confusing -important but often not discussed-like elephant in liv rm -Admirable that part of grand rounds Me -yes conv sci and clinical, BUT recognize pt interest; I got interested when pts asked questions and I realized it took me long time to come up with clear answers to questions. Talk (organiz on slide 3) Handouts- -copies of PowerPoint -handout with detailed alphabetical listing of all supplements talked about today and more -lay handout that can give to pts if time limited or interest is limited -COPYRIGHT-did because of copies on internet, feel free to make copies of lay handout Rmmsc-Info for presentation-developed through cam program at RMMSC

2. I like cartoon -time consuming -frustrating -no answer in the end -ALSO-no health professional involved in processI like cartoon -time consuming -frustrating -no answer in the end -ALSO-no health professional involved in process

3. Levels of Involvement in CAM �Don�t ask, don�t tell� Refer to information sources Provide information Make recommendations Practice therapies ******** Explain levels If at �Don�t ask, don�t tell��I don�t think this is optimal for pt care�if more involved, can direct away from harmful rx and toward possibly beneficial rx My goal with this talk-(�AIT�) -change some attitudes--make you more open to cam -spark some interest -give tools to start talking with patients at a relatively detailed level, esp with diets and dietary supplements (TO DO THIS- -copies of PowerPoint -handout with detailed alphabetical listing of all supplements talked about today and more -lay handout that can give to pts if time limited or interest is limited -COPYRIGHT-did because of copies on internet, feel free to make copies of lay handout)******** Explain levels If at �Don�t ask, don�t tell��I don�t think this is optimal for pt care�if more involved, can direct away from harmful rx and toward possibly beneficial rx My goal with this talk-(�AIT�) -change some attitudes--make you more open to cam -spark some interest -give tools to start talking with patients at a relatively detailed level, esp with diets and dietary supplements (TO DO THIS- -copies of PowerPoint -handout with detailed alphabetical listing of all supplements talked about today and more -lay handout that can give to pts if time limited or interest is limited -COPYRIGHT-did because of copies on internet, feel free to make copies of lay handout)

4. Rocky Mountain MS Center ******** After rev slide�.. �Now for large group of patients with questions about cam, where can they find info?�bookstore is used by many��******** After rev slide�.. �Now for large group of patients with questions about cam, where can they find info?�bookstore is used by many��

5. Dietary Supplements Several types Vitamins Minerals Herbs �Other��enzymes, hormones, amino acids

6. Dietary Supplements Dietary Supplements Health and Education Act (1994) �DSHEA� No standards for quality, safety, efficacy Initiative to Provide Better Health Information for Consumers (www.cfsan.fda) To implement in 2004 Good manufacturing practices (GMPs) Accuracy of content labeling Qualified health claims

8. Herbal Medicine Accessible and popular $5 billion/yr 60 million adults $54/person/yr Many conventional medications are derived from herbs 35% prescription drugs 60% OTC drugs ***** Dshea�passed 1994 Initiative�very positive step, to implement by 2004, details at fda website (www.cfsan.fda.gov (center for food safety and applied nutrition)***** Dshea�passed 1994 Initiative�very positive step, to implement by 2004, details at fda website (www.cfsan.fda.gov (center for food safety and applied nutrition)

9. Herbal Therapy Same mech as drug: eg kava and gabaSame mech as drug: eg kava and gaba

10. Herbal Therapy ?eg sjw??eg sjw?

11. Herbal Therapy Eg cranberry, mild thistleEg cranberry, mild thistle

12. The Good

13. �Modified Swank Diet� Dietary changes Limit saturated fat intake Fish: 2-3 times/week Possible supplements omega 3: fish oil, cod liver oil, EPA/DHA omega 6: sunflower, evening primrose omega 3 + 6: flaxseed oil NOT: borage, black currant seed, spirulina **** Diet changes�also fat < 30% total calories **** Diet changes�also fat < 30% total calories

14. �Modified Swank Diet� May be of interest to some patients NOT instead of FDA-approved medications IMPORTANT Vitamin E: 100-400 IU daily

15. Possibly Effective Herbs St. John�s Wort Depression-possibly Self dx or rx is not safe P450 inducer Photosensitivity, sedation Cranberry UTI prevention-possibly Inhibits bacterial adhesion Better evidence for cranberry than vitamin C NOT for UTI treatment **** SJW-1000s of yrs/2 rec � rct but 23 past rct/not self/p450-antidepr, anticonv, bcp�little sj�s/se�s -used for 1000s of years; blooms around 6/24, feast day of St John the Baptist -mild-mod possible-not severe -at least 23 past RCT, 2 recent �RCT (one with severe, other with � result Zoloft) -multiple poss drug interactions- -2d6-ca ch blockers, protease inhibitors, ssris, ocps�many �little St Johns� with ocps, serotonin syndrome with ssris -3a4-ssris, bz�s, ca ch blockers, aricept -p-glycoprotein-drug transporter inhibitors: multiple drugs (ca ch blockers, abx (eg erythro), antifungals, proton pump inhibitors (omeprazole), protease inh�s Cranberry-antibacti Germans, 1840/ � +studies/ fruct and proanth -antibacterial activity proposed by German scientists in 1840 -some MS pts are prone to UTIs -4 RCT-3+, 1- -proanthocyanidins and fructose may decrease adhesion**** SJW-1000s of yrs/2 rec � rct but 23 past rct/not self/p450-antidepr, anticonv, bcp�little sj�s/se�s -used for 1000s of years; blooms around 6/24, feast day of St John the Baptist -mild-mod possible-not severe -at least 23 past RCT, 2 recent �RCT (one with severe, other with � result Zoloft) -multiple poss drug interactions- -2d6-ca ch blockers, protease inhibitors, ssris, ocps�many �little St Johns� with ocps, serotonin syndrome with ssris -3a4-ssris, bz�s, ca ch blockers, aricept -p-glycoprotein-drug transporter inhibitors: multiple drugs (ca ch blockers, abx (eg erythro), antifungals, proton pump inhibitors (omeprazole), protease inh�s Cranberry-antibacti Germans, 1840/ � +studies/ fruct and proanth -antibacterial activity proposed by German scientists in 1840 -some MS pts are prone to UTIs -4 RCT-3+, 1- -proanthocyanidins and fructose may decrease adhesion

16. Possibly Effective Herbs Valerian Insomnia-possibly Anxiety-uncertain efficacy Spasticity-unstudied Possibly sedating **** Valerian-1000s of yrs -used for thousands of years, used in some root beers -several RCTs -anxiety and spasticity, esp with MS pts (lore for spasticity), but only one anx rct study and no spasticity studies -sedating�may incr ms fatigue or augment sed eff�s of meds such as bacl, zan, bzs Kava -used in South Pacific, first botanical description by Captain Cook�s second voyage -one of few herbs for which active constituent has been identified�kavapyrones, act on GABA-A receptors -insomnia-only one rct **** Valerian-1000s of yrs -used for thousands of years, used in some root beers -several RCTs -anxiety and spasticity, esp with MS pts (lore for spasticity), but only one anx rct study and no spasticity studies -sedating�may incr ms fatigue or augment sed eff�s of meds such as bacl, zan, bzs Kava -used in South Pacific, first botanical description by Captain Cook�s second voyage -one of few herbs for which active constituent has been identified�kavapyrones, act on GABA-A receptors -insomnia-only one rct

17. Ginkgo Biloba Two major constituents flavonoids: antioxidant terpenes: PAF antagonists EAE: effective MS attacks: NOT effective MS cognitive dysfunction possible (AAN,2002) Preventing attacks: unstudied Possible bleeding and seizures **** **describe pics-bilobed leaf, terpene which is cage molecule Unique botany and unique chemistry -�living fossil�-minimal change for 200 M yrs, live as long as 1000 yrs Terpenes-terpene trilactones: bilobalides and ginkgolides; �cage molecules� Terpenes and flavonoids: complex molecules, industrial scale synthesis is not possible **** **describe pics-bilobed leaf, terpene which is cage molecule Unique botany and unique chemistry -�living fossil�-minimal change for 200 M yrs, live as long as 1000 yrs Terpenes-terpene trilactones: bilobalides and ginkgolides; �cage molecules� Terpenes and flavonoids: complex molecules, industrial scale synthesis is not possible

18. Now switch gears and talk about vitamins Vitamin D plays well known role in maintaining bone densityNow switch gears and talk about vitamins Vitamin D plays well known role in maintaining bone density

19. Vitamin D and Calcium Osteoporosis and osteopenia Underdiagnosed and undertreated in MS MS risk factors: nonambulatory, female, low body weight, low sun exposure, ?steroids Disease course EAE: vitamin D is effective MS: vitamin D analog ineffective in small study Some patients may consider reasonable Daily vitamin D doses should be < 2,000 IU

20. Good or Bad?

21. B Vitamins B vitamins generally Used commonly No large MS clinical trial studies Vitamin B12 Subgroup may be B12 deficient If not B12 deficient, no known benefit Vitamin B6 (pyridoxine) Daily doses < 50 mg Vitamin B3 (niacin) Daily doses < 35 mg

22. Antioxidants and MS Possibly beneficial Axonal injury Myelin damage Oxidative markers increased Possibly harmful Stimulate T cells and macrophages **** **NOW-change gears and talk about �grey area� between good and bad **Pic-talk about O2, free radicals, antioxidants**** **NOW-change gears and talk about �grey area� between good and bad **Pic-talk about O2, free radicals, antioxidants

23. Antioxidants and MS Compounds currently being studied

24. Antioxidants and MS Various approaches: Simple approach: fruits and vegetables If supplements taken, modest doses: Vitamin A, <5,000 IU daily Vitamin C, 60-90 mg daily Vitamin E, 100-400 IU daily �Designer antioxidants:� no clear benefit, expensive If high PUFA diet, vitamin E supplements Fruits-2-4 servings Veg-3-5Fruits-2-4 servings Veg-3-5

25. �LDN�Low Dose Naltrexone Opioid antagonist Claims: �boost the immune system�helping those with HIV/AIDS, cancer, and autoimmune diseases.� Positive MS anecdotes Evidence Immune system: variable effects including increased Th1 response EAE: high dose worsens disease MS clinical trials: none Conclusion: unstudied, theoretical risks

26. �Ambrotose� Manufactured by Mannatech Contains polysaccharides Company literature: ��extracts of certain fungi and plants may be of assistance in the treatment of cancer. On investigation, many of these extracts have been found to possess potent immune-stimulating activity�this activity is attributable to complex carbohydrates.� Dr. Ian Tizard

27. �Ambrotose� Claimed to be effective for AIDS, cancer, MS, and many other diseases Anecdotal MS reports MS studies EAE: none MS clinical studies: none Conclusion: unstudied, theoretical risks

28. Prokarin Transdermal patch: histamine and caffeine Two published trials 1999 study: N=55, not controlled, 67% improvement 2002 study: N=27, controlled, possibly fatigue Web-based survey-www.ms-cam.org Total n=1326, 125 users of Prokarin 49% benefit, 66% discontinued Breathing problems, 2%; rash, 44% Cost: $150-250/month **** Not technically a dietary supplement, but thought would mention 1999 study: **Conclusion -gets some people angry because of methods used to promote, but if take evidence based approach you can�t totally �trash� -for some pts it may provide benefit, which could be placebo, and probably is low risk -I put in category of �unstudied�**** Not technically a dietary supplement, but thought would mention 1999 study: **Conclusion -gets some people angry because of methods used to promote, but if take evidence based approach you can�t totally �trash� -for some pts it may provide benefit, which could be placebo, and probably is low risk -I put in category of �unstudied�

29. The Bad

30. �Immune-stimulating� Supplements Usually limited to in vitro studies Sometimes recommended as MS treatment in lay books Herbs Echinacea Alfalfa, astragalus, cat�s claw, garlic, ginseng, others Other supplements Antioxidants: vitamins A, C, E; selenium Others: DHEA, melatonin, zinc ******** **NOW-talk about bad or potentially bad **Slides now will be quite detailed with many different supplements listed- -you have copies and MOST HELPFUL is alphabetical listing that has all this info and more **pic of echinacea [lung ca risk and smokers: study 1: beta-carotene, study 2: vit A and beta-carotene] In theory, may worsen disease or counteract effects of immune-modulating or immune-suppressing medications Evidence against using these supplements is theoretical, but this evidence may still be stronger than evidence (e.g., no evidence, testimonials) used to support their use******** **NOW-talk about bad or potentially bad **Slides now will be quite detailed with many different supplements listed- -you have copies and MOST HELPFUL is alphabetical listing that has all this info and more **pic of echinacea [lung ca risk and smokers: study 1: beta-carotene, study 2: vit A and beta-carotene] In theory, may worsen disease or counteract effects of immune-modulating or immune-suppressing medications Evidence against using these supplements is theoretical, but this evidence may still be stronger than evidence (e.g., no evidence, testimonials) used to support their use

31. Kava Kava Used in South Pacific Kavapyrones-act on GABA-A receptors Anxiety-possibly effective Insomnia-uncertain Possibly sedating ? severe liver toxicity Kava -used in South Pacific, first botanical description by Captain Cook�s second voyage -one of few herbs for which active constituent has been identified�kavapyrones, act on GABA-A receptors -insomnia-only one rct Kava -used in South Pacific, first botanical description by Captain Cook�s second voyage -one of few herbs for which active constituent has been identified�kavapyrones, act on GABA-A receptors -insomnia-only one rct

32. Sedating Herbs Asian ginseng Barberry Black cohosh Calendula Catnip Chamomile Couchgrass Goldenseal Henbane Kava kava Passionflower St. John�s wort Scullcap Siberian ginseng Stinging nettle Valerian This is partial listing of some of the more popular herbs These herbs could worsen MS fatigue or potentiate effects of sedating meds, like Zanaflex, Baclofen, BZs Some of more common on this list ARE This is partial listing of some of the more popular herbs These herbs could worsen MS fatigue or potentiate effects of sedating meds, like Zanaflex, Baclofen, BZs Some of more common on this list ARE

33. Sedating Herbs Asian ginseng Barberry Black cohosh Calendula Catnip Chamomile Couchgrass Goldenseal Henbane Kava kava Passionflower St. John�s wort Scullcap Siberian ginseng Stinging nettle Valerian Some of more common on this list -already talked about-SJW, kava kava, valerian -2 ginsengs -Goldenseal, Passionflower Some of more common on this list -already talked about-SJW, kava kava, valerian -2 ginsengs -Goldenseal, Passionflower

34. Herb-Drug Interactions Immune-modulating and immune-suppressing drugs �Immune-stimulating� supplements Methotrexate �Immune-stimulating� supplements Echinacea: liver toxicity Salicylate-containing herbs Black cohosh, meadowsweet, poplar, sweet birch, willow, wintergreen �Imm stim�-see previous slides MTX -some using as combo Rx -salicylates may incr bld levels (decr excr, incr % free) and incr liver toxicity�Imm stim�-see previous slides MTX -some using as combo Rx -salicylates may incr bld levels (decr excr, incr % free) and incr liver toxicity

35. Herb-Drug Interactions Steroids Asian ginseng, cascara sagrada, ephedra, fenugreek, licorice, lily-of-the-valley, squill SSRIs St. John�s wort Tricyclic antidepressants Belladonna, henbane, mistletoe, St. John�s wort, scopolia Amantadine Belladonna, henbane, pheasant�s eye, scopolia Steroids -most are hypokalemia or hyperglycemia SSRIS -serotonin syndrome has been described TCAs -cholinergic effectsSteroids -most are hypokalemia or hyperglycemia SSRIS -serotonin syndrome has been described TCAs -cholinergic effects

36. The Ugly

37. Dangerous Supplements Recommended for MS Borage seed oil: hepatotoxicity Chaparral: severe hepatotoxicity Comfrey: hepatotoxicity Ephedra: severe hypertension, arrhythmias, death Germanium: renal toxicity, death Lobelia: tachycardia, hypotension, death Scullcap: severe hepatotoxicity Yohimbe: hypertension, hypotension, arrhythmias, death ******** NOW-the UGLY Ones I�ve seen most frequently ARE******** NOW-the UGLY Ones I�ve seen most frequently ARE

38. Dangerous Supplements Recommended for MS Borage seed oil: hepatotoxicity Chaparral: severe hepatotoxicity Comfrey: hepatotoxicity Ephedra: severe hypertension, arrhythmias, death Germanium: renal toxicity, death Lobelia: tachycardia, hypotension, death Scullcap: severe hepatotoxicity Yohimbe: hypertension, hypotension, arrhythmias, death ******** NOW-the UGLY Ones I�ve seen most frequently ARE******** NOW-the UGLY Ones I�ve seen most frequently ARE

40. ****PRACTICE Royalties to cam program at rmmsc****PRACTICE Royalties to cam program at rmmsc

41. Alternative Medicine Websitewww.ms-cam.org >15,000 users MS-relevant CAM information >40 therapies Professional version with references �Forum� Email system Newsletters Surveys

42. References Dietary Supplements and Multiple Sclerosis: A Health Professional�s Guide. Bowling AC, Stewart TM. Demos Medical Publishing, 2004. Alternative Medicine and Multiple Sclerosis. Bowling AC, Demos Medical Publishing, 2001.

43. References �Alternative medicine and multiple sclerosis: an objective review from an American perspective.� Bowling AC, Ibrahim R, Stewart TM. International Journal of MS Care 2000; 2: 14-21. (www.mscare.com) �Current complementary and alternative therapies for multiple sclerosis.� Bowling AC, Stewart TM. Current Treatment Options in Neurology 2003; 5: 55-68.

44. References Dietary Supplements Generally Natural Medicines Comprehensive Database, Jellin JM, Batz F, Hitchens K, Therapeutic Research Faculty, 2002. (www.NaturalDatabase.com) The Health Professional�s Guide to Popular Dietary Supplements, Fragakis A, American Dietetic Association, 2002. Alternative Medicine Generally Complementary and Alternative Medicine: A Desktop Reference, Ernst E, Mosby, 2001. ******** CONCL -some pts and health profs have blanket approach�I hope I�ve shown this is not possible (-like junkyard) -strongly encourage to get involved for several reasons (�EAQ�) -enjoyable-interesting info, broadens view of dis, forces you to think in terms of pt perspective -patients appreciate-improves relations -improve quality of care-avoid dangerous ( -some situations-incr conv and decr cam) ******** CONCL -some pts and health profs have blanket approach�I hope I�ve shown this is not possible (-like junkyard) -strongly encourage to get involved for several reasons (�EAQ�) -enjoyable-interesting info, broadens view of dis, forces you to think in terms of pt perspective -patients appreciate-improves relations -improve quality of care-avoid dangerous ( -some situations-incr conv and decr cam)

45. Conclusions CAM is rewarding Broadens your view of disease Forces you to think from patient perspective Patients appreciate your efforts Can provide CAM information in a timely way Improves patient care -enjoyable-interesting info, broadens view of dis, forces you to think in terms of pt perspective -patients appreciate-improves relations -improve quality of care-avoid dangerous ( -some situations-incr conv and decr cam) -enjoyable-interesting info, broadens view of dis, forces you to think in terms of pt perspective -patients appreciate-improves relations -improve quality of care-avoid dangerous ( -some situations-incr conv and decr cam)

46. Acknowledgments Thomas Stewart, JD, PA-C Ronald Murray, MD Patricia Kennedy, RN, CNP Lee Shaughnessy Gina Ibrahim, PhD Julie Lawton CAM website users Rocky Mtn. MS Center Teva Neuroscience Biogen Serono Berlex HealthOne Foundation Denver Botanic Gardens Hudson Gardens