Docket Management
Docket: 95N-0304 - Dietary Supplements Containing Ephedrine Alkaloids
Comment Number: EC -344

Accepted - Volume 307

Comment Record
Commentor Dr. Arthur Grollman Date/Time 2003-03-19 12:45:45
Organization SUNY Stony Brook University
Category Health Professional

Comments for FDA General
Questions
1. General Comments Having reviewed all published information on ephedra, including the RAND report, I offer the following comments from the perspective of an academic clinical pharmacologist. 1. Danger-- Ephedra alkaloids in various forms marketed for weight loss, with or without caffeine, represent a clear and present danger to a significant fraction of the American public who are persuaded through misleading advertising claims that these substances will a) help them achieve one sustain weight loss and/or b) enhance athletic performance or c) provide energy. Performing a case-controlled study, as suggested by authors of the RAND report, will delay efforts to safeguard the public’s health and it is likely that most institutional review boards would find the proposed study unethical, in light of the weight of present evidence for the dangers, and lack of significant health benefits, of ephedra supplements. 2. Warning label-- A warning label is urgently required along the lines described in the formal announcement. In addition, the FDA recommendation proposed earlier in which the maximum daily dose should not exceed 24 mg should be re-instated. 3. Removal from the market -- Based on published data, ephedra alkaloids with or without caffeine present a significant and unreasonable risk of illness and injury. The FDA should henceforth regulate supplements containing ephedra or ephedra-like substances with sympathomimetic activity, such as synephrine (which replace ephedra in so-called ephedra free products), as an OTC product, not as a dietary supplement. 4. Legislation—changes are urgently needed in the Dietary and Supplement Health Education Act, under which ephedra-containing herbs now classified as a dietary supplements. For specific recommendations for change, I refer you to two commentaries published earlier this year in major medical journals: a) Marcus, D.M and Grollman A.P, Botanical Medicines -- The need for new regulations, NEJM, 347, 2073-2076 (2003). b) Fontanarosa, P.B., Rennie, D. and DeAngelis, C.D. – The need for regulation of dietary supplements – Lessons from Ephedra, JAMA, 289, 1568-1570 (2003). 5. There is important additional data on ephedra-related adverse reactions that was not considered in the RAND report. These include a number of reported deaths and serious adverse reactions that led to the removal of ephedra containing supplements from the Canadian market place, and the more than 30 deaths that occurred in otherwise healthy young adults while serving in the US armed forces. The latter should be requested through the Defense Department, which banned their sale at military commissaries. This information would be very useful even if all identifying information for individuals were removed. These cases should be reviewed using the approach described by Haller and Benowitz in their New Eng J Med article, rather than that utilized by RAND, which greatly underestimates the potential dangers of ephedra. Arthur P. Grollman, M.D.




EC -344