Nutritional and Weight Loss Supplements

Galen Goertzen, PharmD

Group Health Cooperative

Disclosures

• No conflicts of interest or commercial affiliations

• Free of commercial bias

• Includes unlabeled uses for ALL discussed natural medicines

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.

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).

Who is doing it?U.S. CAM Patient Demographics

• 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

2007 Statistics on CAM Use in the United States, http://nccam.nih.gov/news/camstats/2007/

60-70% do NOT disclose this information to their doctors

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

What’s the concern?Differences in Regulatory Standards

Drugs vs. Supplements: Different Regulatory Standards  Rx Drugs Supplements

Proof of Safety Required Not required*

Proof of Effectiveness Required Not required

Post-marketing Surveillance Required Not required**

Good Manufacturing Practices (GMPs) Pharmaceutical GMPs Food GMPs***

Disease Treatment Claims Allowed Not allowed

* 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

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

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

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???

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/

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 Field http://www.cochrane.orgNatural Medicines Watch™

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

Bring Safety and Efficacy Together

Developed by Natural Medicines Comprehensive Database

How to help patients select a natural supplement

Step #3: Product Quality AssessmentLook 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.

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

What patients are taking

Fish Oilomega-3 fatty acids eicosapentaenoic acid (EPA) and

docosahexaenoic acid (DHA) EffectiveHypertriglyceridemia. 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 effectiveCardiovascular 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)

AdultsLikely 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 lactationLikely safe

ChildrenPossibly safe

Consider recommending in adults

Echinaceaechinacea angustifolia; echinacea pallida; echinacea purpurea

AdultsLikely 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.

ChildrenPossibly safe when used orally, short-term; might increase the risk of rash in some children.

Possibly EffectiveCommon 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 ConcernsEchinacea products are frequently mislabeled or may contain no Echinacea. Echinacea products have been commonly adulterated. Some have been contaminated with selenium, arsenic, and lead.

Don’t recommend this product

Glucosamine SULFATE & Chondroitin SULFATEAdultsLikely 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.

OsteoarthritisLikely EffectiveClinical 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

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

Nausea TreatmentsPyridoxine (B6) and Ginger

Pyridoxine: ACOG considers pyridoxine a first line option for N/V of pregnancy - however, it should not be used long-term or without medical supervision25 mg every 8 hours better than placebo Lower doses also help for nauseaDoxylamine 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

AdultsBoth 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 safeConsider recommending

Summary of Select Supplements in Adults*Safety/Efficacy Likely Safe Possibly Safe Insufficient

EvidencePossibly Unsafe

Likely Unsaf

e

Unsafe

Effective Fish Oil

Likely Effective

Co-Enzyme Q10Ginger Glucosamine SulfatePyridoxine

Possibly Effective

Chondroitin SulfateFlaxseedEchinaceaGarlicGinkgoSiberian Ginseng

American GinsengPanax Ginseng

Insufficient Evidence

Glucosamine HCl

Possibly Ineffective

Consider recommending this product. Don't recommend using this product. Recommend against using this product.

*Listed are the best efficacy and safety ratings for each product, different doses and uses may have different ratings.

Weight Loss Supplements

• Appetite suppression – hoodia, Fen-phen

• Metabolism boosters – ephedrine, bitter orange, caffeine

•Inhibition of nutrient absorption – orlistat (Xenical), barley, bean pod

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

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

Summary of Select Weight Loss Supplements in Adults*

Safety/Efficacy Likely Safe Possibly Safe Insufficient Evidence

Possibly Unsafe

Likely Unsafe

Effective

Likely Effective

Possibly Effective

- Blond psyllium (for orlistat side effects)- Calcium

- Conjugated linoleic acid

Ephedra

Insufficient Evidence

- Barley- Chromium- St John’s Wort

- Bean pod- Chitosan- Glucomannan- Guggul- pyruvate

- Cha de bugre- Hoodia- Usnea

-5 HTP- Bitter orange

Aristolochia

Possibly Ineffective

- Guar gum - Garcinia- Inulin

Consider recommending this product. Don't recommend using this product. Recommend against using this product.

*Listed are the best efficacy and safety ratings for each product, different doses and uses may have different ratings recreated from Pharmacist’s Letter

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.”

Patient Friendly Information

Fact sheets on dietary supplements from the National Institutes of Health: http://nccam.nih.gov/

Patient Handouts from Natural Medicines Database or Natural Standard

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!