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1 Herbs & Supplements Did you remember to take your Gingko today ? Robert Baldor, MD Professor Family Medicine & Community Health 2 Why patients use CAM • • • • • • • 38% of US/$34 billion out-of-pocket in 2007 Arthritis/Back/Neck/Joint pain Anxiety Cholesterol management URIs Headache/Migraine Insomnia 3 A Clinician’s Perspective • What’s available • Efficacy • Safety 4 Herbal Therapies (Top Dozen) • • • • • • Gingko biloba St John’s Wort Ginseng Garlic Echinacea Saw Palmetto • • • • • • Kava Kava Valerian Soy Evening Primrose Grape seed Milk Thistle 5 Gingko Extracts • • • • Ancient Chinese herbal treatment Maidenhair tree leaves Effects from flavonoids - antioxidant Reduces capillary fragility, vasodilator 6 Ginkgo Considerations • Recommended to stabilize cognition in Alzheimer's or multi-infarct dementia; improves walking with claudication • 120-240 mg BID, TID • Appears safe • Avoid with anticoagulants (2002 Cochrane) 7 Marketed For ... • Memory enhancement • Improved concentration • No evidence for improved memory/concentration in normal, healthy individuals (NEJM 2002) 8 St. John’s Wort • Flowering plant (H. perforatum) • Hypericin, a naphthodianthrone is the main active ingredient • Inhibits neurotransmitter uptake of serotonin, norepinephrine, & dopamine • Binds to GABA receptors 9 St. John’s Wort • Outsells Prozac in Germany 7:1 • Meta-analysis - appears effective as low doses of standard antidepressants • Phototoxicity 10 Depression Consumers Report 2004 11 Ginseng • From genus panax (panacea!) • An adoptogen - no studies compared to stimulants such as caffeine • Considered safe • Siberian Ginseng – An abundant Russian herb thought to have the same properties as Ginseng – No published studies 12 The wonder herb . . . • Ginseng is expensive - study of 54 products 85% contained little or no ginseng, but …. varying amounts of caffeine! • Glacial Tropical Citrus Vitamin Water 21 mg of caffeine – Coke has 24 mg! 13 Red Bull… • Taurine (essential amino acid) 1000mg • Glucuronolactone (conjugates with toxic metabolites for excretion) 600 mg • B complex vitamins • Caffeine 80 mg (24 gms in Coke) • Sugar 27 grams (39 gms in Coke) 14 • B Vitamins – Niacin: 30 milligrams, or 150% of the RDV – Vitamin B6: 40 milligrams, or 2,000% of RDV – Vitamin B12: 0.5 milligrams , or 8,000% of RDV and…… – As much caffeine as a cup of premium coffee • A cup (8oz) of Starbucks has 180mg of caffeine Garlic (allium sativum) • • • • Organosulfer compounds May block carcinogens in food Garlic extract - decreases cholesterol 7% Available in ‘odor free’ capsules • Active agent (allium) is odoriferous 16 Long regarded to deter vampires • Norwegian experiment with leeches (lack of vampires) • Garlic-smeared hand preferred in 66% of time • Leeches attached in 14.9 secs vs 44.9 secs when going to the non-garlic hand (p < 0.05) • The traditional belief that garlic can deter vampires is probably wrong • The reverse may in fact be true Tidsskr Nor Laegeforen. 1994 Dec 10;114(30):3583-6. 17 Echinacea • For Rx of colds ($100 million in sales) • Appears to alleviate some cold symptoms no evidence for cure • 1998 randomized trial showed no ability to prevent colds (JFP 1999) 18 Zinc & Colds • Inhibits rhinovirus in tissue culture • Meta-analysis showed no conclusive evidence for reducing colds (Arch IM 1997) • Controlled trial of lozengers - ineffective & side effects - taste, N&V (JAMA 1998) • Randomized blinded trial of nasal gel – decreased length of cold by 2 days (ENT J 2000) • Improved Rx vs. antibiotics ? 19 Saw Palmetto • Appears safe and effective for BPH, comparable to finasteride (Proscar) • Inhibits the 5a reductase conversion of testosterone to dihydrotestosterone (a prostate growth stimulator) • 160 mg bid or 320 mg qd JAMA1998; AFP2003 20 Anxiolytics GABA Binding Activity • Valerian (insomnia) • Kava kava (anxiety) • Chamomile (insomnia) 21 Valerian • Some efficacy for insomnia • Unclear evidence for anxiety • Appears safe, maybe helpful to wean from benzodiazepines dependence • 300 - 600 mg before bedtime or as tea (2-3 gm of dried root) AFP 2003 22 KAVA & Hepatotoxicity • 70 reports of kava induced liver failure, with 4 deaths and 7 liver transplants • FDA 2002 advisory – avoid kava if having or at risk for liver disease • Last year UK banned Kava sales 23 Phytoestrogens for Menopause • Plant compounds resembling estradiol • Isoflavones most potent • Supplements of unclear benefits v. foods - Soy, Tofu, Black Cohosh • Consider for mild menopausal Sx • Reports of Black Cohosh induced hepatitis 24 Relief of Hot Flashes Consumers Report 2004 25 Milk Thistle • Flavonoid complex called silymarin • Used for improving liver function in hepatitis, cirrhosis • Meta- analysis – appears safe but no clear benefit…. Am J Med 2002 26 “Not much - just flushing out my arteries.” The NewYorker 27 What about Red Wine? • ‘The French paradox’ – low incidence of CVD – but a relatively high fat diet. • Grapes contain flavonoids (resveratol), potent antioxidants - ? account for positive effects • Red wine has 160ug/oz; peanuts 70 ug/oz • Grape juice is not fermented –negligible amounts • No enough evidence to conclude that red wine is more effective than other alcoholic bevearges in lowering CVD risk 28 “It’s a B-complex. Didn’t they used to put chocolate on the pillow?” 29 Chocolate (flavonoids) • 1 oz has as much flavonoids as 6 apples, 5 cups of tea or 2 glasses of red wine • Flavonoids reduce platelet aggregation • Decreased platelet activation 6 hours after eating chocolate – Didn’t measure glucose or lipid levels (MARS funded) • Recent meta-analysis dark cocoa products reduce BP 5/2 mmHg (AJH, 2010) 30 Ginger (zigiber officinale) • • • • Used for centuries to treat nausea Post-op nausea, motion & sea sickness Chemotherapy results disappointing Commonly used but not recommended for pregnancy (bleeding, miscarriage) 31 “Michael has had an interesting side-effect from taking St. John’s Wort” 32 FDA Approval • Drugs must be safe and effective • Average $230 million & 12 years • No patent to recoup costs for herbs 33 Dietary Supplement Act Of 1994 • Applies to ‘dietary supplements’ – vitamins, minerals, herbs, natural substances • Health claims not specified on label • FDA must prove unsafe before removing 34 Health Foods?….L-Trypthophan • An amino acid - assumed safe • Used for insomnia • Eosinophilia myalgia syndrome developed – 38 deaths!! • Banned by FDA in 1990 35 FDA Concerns …. • Over 2000 reports of adverse effects in 2009 • No manufacturing oversight: – 1/3rd of supplements <50% of stated ingredients (Ginseng products only contain caffeine) – Niacin product contained 10x safe level ( GI distress, hepatic damage, MI) • Proposed rule to prevent the sale of supplements that are sub- or super- potent, that contain drugs, or contaminants (i.e. bacteria, pesticides, glass, lead) 36 “Something from the supplement cart?” The NewYorker 37 Common Supplements • Glucosamine/ chondroitin • CoQ-10 • Melatonin • Amino Acids • • • • • Fish Oils/omega FA DHEA Acidophilus Chromium Sports enhancement 38 Glucosamine & Chondroitin • • • • Glucosamine (crab shell chitin) Chondritin (cow cartilage) The ‘raw materials for new cartilage’ Evidence for pain & disability relief in osteoarthritis, comparable to ibuprofen & acetaminophen • Safe – few side effects Cochrane Review 2005 39 Consumers Report 2004 40 Coenzyme Q10 • • • • • • • • Fat soluble vitamin Involved in mitochondrial oxidation producing ATP Some anti-oxidant properties In CHF, cardiac tissues under ↑’d oxidative stress w/decreased tissue levels of Q10 Approved in Japan since 1974 to treat CHF Some evidence for benefit in Parkinson’s & mitochondrial diseases 200mg qday lower BP 16/10 mmHG Safe but expensive (50-1200 mg/day) AFP 2005 41 Melatonin • Modified amino acid (tryptophan) • Released from pineal gland by diminishing light levels • Role in humans not fully elucidated • Small, conflicting sleep studies 42 Melatonin for Sleep • • • • Induces sleep if plasma levels are low Shift workers Jet Lag 0.1 – 10 mg qhs 43 Insomnia Consumers Report 2004 44 Fish Oils & Omega 3 fatty acids • Fish oil supplements supported by RCTs – Lower triglycerides – Reduce CAD and stroke risk with known CVD disease – Lowers BP slightly (10/4 mmHg) • No evidence for primary prevention 45 DHEA (Dihydroepiandrosterone) • Produced by adrenals, unclear role outside of Rx for adrenal insufficiency • Converted to estrogens and testosterone • Plasma levels decline with age • Schedule II - an anabolic steroid • DHEA supplements are Yam extracts, not converted to DHEA 46 Marketed as... • • • • Anti-aging Hirsutism & deeping voice seen Concern for prostate or breast cancer Series of studies 1995 - 1998 in J. Clin Endocrinology - some perceived sense of well being, but no obvious benefits 47 Acidophilus - a probiotic (organism used medically) • Lactobacillus acidophilus - bacteria that live in the intestine and vagina • Good evidence to support L. acidophilus vaginal suppositories to Rx bacterial vaginosis • Some studies suggest eating yogurt enriched with L. acidophilus may be similarly beneficial • Benefit in colic treatment ? • Marketed to improve digestion, no clear evidence of benefit 48 Chromium for weight loss ?? • • • • • Essential trace mineral - Insulin cofactor China & Israeli studies for DM treatment Diabetics not chromium deficient Mixed results from a variety of studies Safe up to 1000mcg/day The Medical Letter 2006 49 Marketed To.... • Loose fat • Boost energy • ... no published support for such effects 50 Weight loss ….Health Foods?? • Metabolife contains Ma Hung • Bitter orange extract contains synephrine • Chomper is a natural laxative, contains digitalis - induces arrhythmias • Tryptophan & phenylalanine - amino acids ? efficacy 51 Health Foods?…. • Associated Press 5/22/00 …Herbalife Founder Mark Hughes dies at the age of 44 of ... .. Natural causes! 52 Ma-Huang or Ephedra • • • • MetaboLife, Herbal Ecstasy Contains Ephedrine Linked to 155 deaths & strokes Banned by NFL, NCAA after heat stroke deaths while using the supplement • FDA Ban in 2004 • Ban overturned, FDA overstepped authority 53 “I’m taking you off wine, women and song and putting you on broccoli” 54 A Clinician’s Perspective ..... varying approaches • Acceptance - ask about & tolerate use of herbal products by patients • Endorsement - accept patient use of natural products as initial therapy, monitor for effects • Integration - prescribe herbs with advice on use, dosing, etc. 55 56 Resources • www.NaturalStandard.com • NIH CAM Center (nccam.nih.gov) • NIH Office of Dietary Supplements (odp.od.nih.gov/ods/) • Food & Drug Administration (fda.gov) • www.consumerlab.com • Medical Letter • Published studies 57 Current Consensus …the best nutritional strategy for promoting optimal health & reducing the risk of chronic disease is to choose wisely from a wide variety of foods, with emphasis on anti-oxidant rich fruits, vegetables & whole grains . AHA 2002 ADA 2002 58 Best Advice . . . • Buy from well-known national companies • Label includes: – Herbs common & scientific name – Manufacture’s name & address – Dosing guidelines – Potential side effects – Batch & Lot number and expiration date • US Pharmacopoeia verification seal 59 60 A Final Thought….. • The Japanese eat very little fat and suffer fewer heart attacks than the British or Americans • However, the French eat a lot of fat and also suffer fewer heart attacks than the British or Americans • The Germans drink very little red wine and suffer fewer heart attacks than the British or Americans • While the Italians drink excessive amounts of red wine & suffer fewer heart attacks than British or Americans • Conclusion: Eat and drink what you like. Speaking English is apparently what kills you! 61 62