Nutritional and Weight Loss Supplements

1. Nutritional and Weight Loss Supplements Galen Goertzen, PharmD Group Health Cooperative

2. Disclosures • No conflicts of interest or commercial affiliations • Free of commercial bias • Includes unlabeled uses for ALL discussed natural medicines

3. Objectives • Discuss the process by which dietary supplements reach the US market and the FDA’s role in that process • Provide brief overview of most common dietary supplements used by adults in the U.S. • Discuss the evidence for efficacy and safety for the various dietary and weight loss supplements • Identify evidence-based natural medicine resources for clinicians and members.

4. Background • Use of herbal products has increased by nearly 400% during the last decade. • There appears to be an implicit belief that, because herbal remedies are natural, they are safe. • The FDA does not regulate herbs for content and safety. • Dietary Supplement and Nonprescription Drug Consumer Protection Act serious adverse event reporting – effective on products labeled after December 22, 2007 (enforcement begins 1/1/2010).

5. 38% of adults 41% of adults aged 60-69 1 in 9 children 42.8% women 55.4% of people with higher levels of education - Masters, doctorate or professional 60% of pregnant and breast-feeding women Who is doing it?U.S. CAM Patient Demographics 60-70% do NOT disclose this information to their doctors 2007 Statistics on CAM Use in the United States, http://nccam.nih.gov/news/camstats/2007/

7. What’s the concern?Not all Dietary Supplements are Created Equal

8. What’s the concern?Differences in Regulatory Standards * Premarket notification is required for "new dietary ingredients" which have not been previously marketed. However, proof of safety is not required.** Starting in 2007 dietary supplement manufacturers are required to report adverse event information that they receive to the FDA.*** Dietary supplement GMPs are in development by the FDA

9. What’s the concern?Safety and other concerns • Toxicity – may be inherently unsafe when orally ingested i.e. ephedra, aristolochic acid • Adulterants – contamination, particularly with imported products – i.e. Man Up Now and Vigor-25 contain sulfoaildenafil • Dosage variability – active ingredients may vary wildly between different products – i.e. hoodia • Risks to special populations – what is effect in pregnancy, children, kidney disease • Economic risks – May be considerably more expensive than FDA approved products on market – Airborne, Red Yeast Rice vs. lovastatin

10. What’s the concern?Drug-Supplement Interactions • The POTENTIAL for interactions is huge. • We know that drug-supplement interactions do in FACT occur based on case reports and some clinical studies. 1. Pharmacokinetic These interactions occur when absorption, distribution, metabolism, or elimination (ADME) of a drug is altered. • Calcium: quinolone antibiotics, tetracycline, bisphoshonates, levothyroxine • St. John’s wort: CYP3A4 substrates 2. Pharmacodynamic interactions can often be predicted based on the pharmacology of a drug and supplement. These interactions can occur when the pharmacological effects of two products are additive or oppositional. • Kava: Hepatotoxic drugs • Ginkgo: Antiplatelet drugs

11. What’s the Concern?Fad ingredients particularly susceptible to adulteration and fraud • Products for “Sexual enhancement” - > 80 FDA actions • Claim to work in minutes or hours or have long-lasting effects up to 24-72 hours • Weight Loss products - >70 FDA actions • “Bodybuilding” products - > 80 FDA actions • Claim to be legal alternative to anabolic steroids • Watch particularly for products marketed in foreign language or through mass e-mails • Are the claims too good to be true???

12. What’s the concern?$2.5B Spent, No Alternative Med Cures • Ten years ago the government set out to test herbal and other alternative health remedies to find the ones that work. • No better than PLACEBO in big studies funded by the NIH National Center for Complementary and Alternative Medicines. • Echinacea for colds. • Ginkgo biloba for memory. • Glucosamine and chondroitin for arthritis. • Black cohosh for menopausal. • Saw palmetto for prostate health. • Shark cartilage for cancer. • The lone exception: ginger capsules may help chemotherapy nausea. • Studying herbals is tough because they are not standardized as prescription drugs are required to be. http://nccam.nih.gov/

13. Evidence based information Complementary & Alternative Medicine Databases • Natural Medicines Comprehensive Database • Natural Standard - AAFP recommended resource • ConsumerLab.com - A Quality "Watchdog" for Herbal and Dietary Supplements CAM on PubMed http://nccam.nih.gov/research/camonpubmed/ Cochrane Database – search in reviews by topic and select Complementary Medicine Fieldhttp://www.cochrane.org Natural Medicines Watch™

14. How to help patients select a natural supplement Step #1: Safety Assessment • Safety Rating: Likely Safe to Unsafe Step #2: Effectiveness Assessment • Effective to Likely Ineffective

15. Bring Safety and Efficacy Together Developed by Natural Medicines Comprehensive Database

16. How to help patients select a natural supplement Step #3: Product Quality Assessment Look for the USP-Verified Mark • USP standards are enforceable by the FDA. • The mark represents that USP has rigorously tested and verified the supplement to assure the following: • What's on the label is in fact in the bottle. • The supplement does not contain harmful levels of contaminants. • The supplement will break down and release ingredients in the body. • The supplement has been made under good manufacturing practices. Practice Pearl – National Vitamin Company is USP verified for disintegration and dissolution standards. They maintain Pharmaceutical Standards of GMP and are in compliance with Pharmacopeia standards for measuring identity, strength, quality, and purity of active ingredients.

17. USP Dietary Supplement Verification Program • Comprehensive laboratory testing of supplements against USP standards • Thorough manufacturing and quality control document review • On-site manufacturing facility audit for compliance with USP standards and FDA current Good Manufacturing Practices • Random off the shelf testing to confirm that products continue to meet USP standards

18. What patients are taking

19. Effective Hypertriglyceridemia. Fish oil from supplements or from dietary sources can reduce triglyceride levels by 20% to 50% Lovaza is FDA approved as adjunct to diet therapy in the treatment of hypertriglyceridemia at 4g/day – no evidence of increased effectiveness Likely effective Cardiovascular disease. Consuming fish oil from dietary sources (fish), two servings of fatty fish/week, seems to reduce the risk of developing cardiovascular disease (primary prevention) Adults Likely safe when used orally and appropriately. Doses of 3 grams per day and less can be safely used by most people. Possibly unsafe in large amounts. Doses greater than 3 grams per day can inhibit blood coagulation and potentially increase the risk of bleeding and might also suppress immune response. Pregnancy and lactation Likely safe Children Possibly safe Fish Oilomega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) Consider recommending in adults

20. Adults Likely safe when used orally, short-term. Several formulations of echinacea have been used safely in trials lasting up to 12 weeks. Pregnancy: possibly safe when used orally, short-term. Lactation: insufficient reliable information available; avoid using. Children Possibly safe when used orally, short-term; might increase the risk of rash in some children. Possibly Effective Common cold. Taking some echinacea preparations seems to modestly reduce symptom severity and duration, possibly by about 10% to 30% Vaginal candidiasis. Taking echinacea orally in combination with a topical antifungal cream seems to be effective for preventing recurrent vaginal yeast infection. Product Concerns Echinacea products are frequently mislabeled or may contain no Echinacea. Echinacea products have been commonly adulterated. Some have been contaminated with selenium, arsenic, and lead. Echinaceaechinacea angustifolia; echinacea pallida; echinacea purpurea Don’t recommend this product

21. Glucosamine SULFATE & Chondroitin SULFATE Adults Likely safe when used orally. Glucosamine has been used safely in multiple clinical trials lasting from 4 weeks to 3 years. Chondroitin sulfate has been used safely in studies lasting from 2 months to 6 years. Possibly safe when used IM short-term. Glucosamine sulfate in combination with chondroitin sulfate, shark cartilage, and camphor appears to be safe when applied topically on an as-needed basis for up to eight weeks. Pregnancy and Lactation: Insufficient reliable information available; avoid using. Osteoarthritis Likely Effective Clinical trials show that glucosamine sulfate orally significantly improves symptoms of pain and functionality compared to placebo in patients with osteoarthritis of the knee in studies up to 3 years. Note: There is conflicting evidence about the effectiveness of glucosamine HCl. Possibly effective Clinical research on the effectiveness of chondroitin sulfate is inconsistent. Combination products of glucosamine plus chondroitin are probably effective, but there is no reliable evidence that it is better than glucosamine alone. Consider recommending in adults Don’t recommend these products

22. L-Methylfolate (Deplin) • Dietary folate is a mixture of different forms of folate – converted to L-methylfolate enzymatically • Compared to folic acid in pregnancy and heart disease – slightly more bioavailable but with continued use there is no difference in blood levels • Safety appears to be equivalent to folic acid – avoid high dose use in elderly (just like folic acid) due to possible increased cancer risk • No need to recommend

23. Pyridoxine: ACOG considers pyridoxine a first line option for N/V of pregnancy - however, it should not be used long-term or without medical supervision 25 mg every 8 hours better than placebo Lower doses also help for nausea Doxylamine added when patients don't respond to pyridoxine alone Ginger: 250 mg four times daily better than placebo and comparable to vitamin B6. Takes approximately 3 days to see benefit. Chemotherapy related nausea: Contradictory evidence of effectiveness for CINV. PONV: 1 gram one hour prior to surgery seems to reduce the incidence of 24-hour postoperative nausea and vomiting Adults Both likely safe when used orally. Pyridoxine is possibly safe in amounts exceeding the recommended dietary allowance and possibly unsafe in doses exceeding 1000 mg daily or total doses of 1000 grams (neuropathy). Pregnancy: Pyridoxine is likely safe; but possibly unsafe when used in excessive doses. There is some concern that high-dose maternal pyridoxine can cause neonatal seizures. Ginger is possibly safe in pregnancy Children: Pyridoxine is likely safe Nausea TreatmentsPyridoxine (B6) and Ginger Consider recommending

24. Consider recommending this product. Don't recommend using this product. Recommend against using this product. Summary of Select Supplements in Adults* *Listed are the best efficacy and safety ratings for each product, different doses and uses may have different ratings.

25. Weight Loss Supplements • Appetite suppression – hoodia, Fen-phen • Metabolism boosters – ephedrine, bitter orange, caffeine • Inhibition of nutrient absorption – orlistat (Xenical), barley, bean pod

26. Weight Loss Supplements • Hoodia – succulent from South Africa – difficult to find so often substituted with cactus no evidence that it is effective • Ephedrine (not ephedra) – similar to PPA – when combined with caffeine may lead to wt loss – also ↑risk of psychiatric symptoms, autonomic hyperactivity and palpitations • Chromium – small effect if any

27. Weight Loss Supplements • Bitter Orange – linked to reports of ischemic stroke and cardiotoxicity including tachyarrhythmia, cardiac arrest, syncope, angina, MI, ventricular arrhythmia, and death in otherwise healthy patients • Conjugated linoleic acid (CLA) - may increase lean body mass but not decrease total body weight – may be associated with insulin resistance

28. Consider recommending this product. Don't recommend using this product. Recommend against using this product. Summary of Select Weight Loss Supplements in Adults* *Listed are the best efficacy and safety ratings for each product, different doses and uses may have different ratings recreated from Pharmacist’s Letter

29. HCG diet • Human Chorionic Gonadotropin given by IM injection or now sublingually in addition to 500-800 calorie diet • Shown to be no more effective than 500-800 calorie diet by itself • Promoted by Kevin Trudeau in his book, “The Weight Loss Cure “They” Don’t Want You to Know About.”

30. Patient Friendly Information Patient Handouts from Natural Medicines Database or Natural Standard Fact sheets on dietary supplements from the National Institutes of Health: http://nccam.nih.gov/

31. Summary • As with conventional drugs, careful consideration of the risk vs. benefit should be done before recommending natural medicines. • Products without clear benefit and safety should be avoided. • Products that are likely safe and effective or likely effective and are high quality (e.g. USP-Verified Mark) are appropriate to recommend. • Ask your patients specifically about herbal products • Find a good consultation source, whether it is a good database or a good pharmacist!