Docket Management
Docket: 95N-0304 - Dietary Supplements Containing Ephedrine Alkaloids
Comment Number: EC -1343

Accepted - Volume 326

Comment Record
Commentor Dr. Arthur Grollman Date/Time 2003-04-04 13:03:23
Organization SUNY at Stony Brook
Category Health Professional

Comments for FDA General
Questions
1. General Comments Kreider, Greenwood, Greenwood and Leutholtz have posted a detailed comment on this docket, describing themselves as researchers of “national and international distinction” from a “leading laboratory that works on the safety and efficacy of national supplements”. Surprisingly, citations to this research do not appear among the 41 references listed in this comment. Many of the statements by Kreider et al are inaccurate and the thrust of the document is misleading. For example, they state that the authors of the Rand Report “concur” with the central claim made by the supplement industry; namely, that “ephedra can safely promote weight loss in healthy but overweight populations” when, in fact, the authors concluded that, after reviewing the complete literature on that subject, they were unable to evaluate events with a risk of less than 1 per 1000. Kreider et al describe a recent report by Boozer et al (1) as the “most thorough study of the safety of ephedra”. This report, funded by Metabolife, was discredited when it was discovered that the ephedra and placebo used in the study had been mislabeled. Kreider et al cite approximately 1,500 reports of adverse reactions of ephedra reported to the FDA since 1993, but fail to mention that the Office of the Inspector General of HHS reported that less than 1% of adverse effects are reported to FDA under the current voluntary system (2). The correctness of the OIG analysis was confirmed (a) when the manufacturer of Metabolife revealed the dramatic under-reporting of adverse reactions to their product and (b) by the large number of adverse reports to ephedra reported to Poison Control Centers (3). It is misleading to compare safety and efficacy of ephedra to over the counter drugs. Medications must be evaluated according to their health benefit relative to risk. All drugs are toxic for some individuals. The effectiveness of aspirin in relieving pain and as an anticoagulant is unquestioned. In contrast, the benefit of ephedra at least is limited to the loss of 1-2 pounds a month more than placebo for studies of up to 4-6 months. And although obesity is associated with various health problems, this modest degree of drug-induced weight loss has never been shown to reduce the increased morbidity observed in obese patients. Our personal responses to the specific questions posed by FDA are recorded elsewhere on this docket. Based on our published analysis of this problem (4), we concluded that ephedra and related sympathometic amines (including those found in so-called “ephedra-free” supplements, are drugs, not dietary supplements, and should be regulated as such by the FDA. Arthur Grollman, M.D. Professor of Medicine and Pharmacological Sciences State University of New York at Stony Brook School of Medicine Donald Marcus, M.D., Professor of Medicine and Microbiology Baylor University School of Medicine **In contrast to the disclaimer by Kreider et al, the comments we have placed on this docket reflect the scientific opinions of our relevant professional organizations; namely, the American Medical Association and the American Association for Pharmacology and Experimental Therapeutics. References: 1. Boozer CN, Daly PA, Homel P, Solomon JL, Blanchard D, Nasser JA, Strauss R, Meredith T. Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial. Int J Obes Relat Metab Disord, 26:593-604, 2002. 2. “Adverse event reporting for dietary supplements: an inadequate safety valve. Washington, DC: Office of Inspector General, April 2002 (Report no. OEI-01-00-00180). 3. Bent S., Tiedt TN, Odden MC, Shlipak MG. The relative safety of ephedra compared with other herbal products. Ann Intern Med, 138:468-471, 2003. 4. Grollman AP and Marcus DM. Botanical Medicines – The need for new regulations. N Engl J Med, 347:2073-2076, 2002.




EC -1343