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Previous Volume 343:1833-1838 December 21, 2000 Number 25 Next

	Full Text PDF Editorial by Fleming, G. A. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Dietary supplements that contain ephedra alkaloids (sometimes called ma huang) are widely promoted and used in the United States as a means of losing weight and increasing energy. In the light of recently reported adverse events related to use of these products, the Food and Drug Administration (FDA) has proposed limits on the dose and duration of use of such supplements. The FDA requested an independent review of reports of adverse events related to the use of supplements that contained ephedra alkaloids to assess causation and to estimate the level of risk the use of these supplements poses to consumers.

Methods We reviewed 140 reports of adverse events related to the use of dietary supplements containing ephedra alkaloids that were submitted to the FDA between June 1, 1997, and March 31, 1999. A standardized rating system for assessing causation was applied to each adverse event.

Results Thirty-one percent of cases were considered to be definitely or probably related to the use of supplements containing ephedra alkaloids, and 31 percent were deemed to be possibly related. Among the adverse events that were deemed definitely, probably, or possibly related to the use of supplements containing ephedra alkaloids, 47 percent involved cardiovascular symptoms and 18 percent involved the central nervous system. Hypertension was the single most frequent adverse effect (17 reports), followed by palpitations, tachycardia, or both (13); stroke (10); and seizures (7). Ten events resulted in death, and 13 events produced permanent disability, representing 26 percent of the definite, probable, and possible cases.

Conclusions The use of dietary supplements that contain ephedra alkaloids may pose a health risk to some persons. These findings indicate the need for a better understanding of individual susceptibility to the adverse effects of such dietary supplements.

Source Information

From the Division of Clinical Pharmacology and Experimental Therapeutics, Departments of Medicine and Biopharmaceutical Sciences, University of California, San Francisco, and the California Poison Control System, San Francisco Division — both in San Francisco.

Address reprint requests to Dr. Benowitz at the Division of Clinical Pharmacology and Experimental Therapeutics, University of California, San Francisco, Box 1220, San Francisco, CA 94143-1220, or at nbeno{at}itsa.ucsf.edu.

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• Lopez-Garcia, E., van Dam, R. M, Rajpathak, S., Willett, W. C, Manson, J. E, Hu, F. B (2006). Changes in caffeine intake and long-term weight change in men and women. Am. J. Clin. Nutr. 83: 674-680 [Abstract] [Full Text]  
• Calfee, R., Fadale, P. (2006). Popular Ergogenic Drugs and Supplements in Young Athletes. Pediatrics 117: e577-e589 [Abstract] [Full Text]  
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• Bui, L. T, Nguyen, D. T, Ambrose, P. J (2006). Blood Pressure and Heart Rate Effects Following a Single Dose of Bitter Orange. The Annals of Pharmacotherapy 40: 53-57 [Abstract] [Full Text]  
• Smolinske, S. C. (2005). Herbal Product Contamination and Toxicity. Journal of Pharmacy Practice 18: 188-208 [Abstract]  
• Woodward, K N (2005). The potential impact of the use of homeopathic and herbal remedies on monitoring the safety of prescription products. Hum Exp Toxicol 24: 219-233 [Abstract]  
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• Richard, C. L, Jurgens, T. M (2005). Effects of Natural Health Products on Blood Pressure. The Annals of Pharmacotherapy 39: 712-720 [Abstract] [Full Text]  
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• Bent, S., Tiedt, T. N., Odden, M. C., Shlipak, M. G. (2003). The Relative Safety of Ephedra Compared with Other Herbal Products. ANN INTERN MED 138: 468-471 [Abstract] [Full Text]  
• Chyka, P. A. (2003). Health Risks of Selected Performance-Enhancing Drugs. Journal of Pharmacy Practice 16: 37-44 [Abstract]  
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• Corns, C, Metcalfe, K (2002). Risks associated with herbal slimming remedies. The Journal of the Royal Society for the Promotion of Health 122: 213-219 [Abstract]  
• Skinner, C. M., Rangasami, J. (2002). Preoperative use of herbal medicines: a patient survey. Br J Anaesth 89: 792-795 [Abstract] [Full Text]  
• Markman, M. (2002). Safety Issues in Using Complementary and Alternative Medicine. JCO 20: 39s-41 [Abstract] [Full Text]  
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• Metcalfe, K., Corns, C., Fahie-Wilson, M., Mackenzie, P. (2002). Chinese medicines for slimming still cause health problems. BMJ 324: 679-679 [Full Text]  
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• Blanck, H. M., Khan, L. K., Serdula, M. K. (2001). Use of Nonprescription Weight Loss Products: Results From a Multistate Survey. JAMA 286: 930-935 [Abstract] [Full Text]  
• Boucher, J. L., Shafer, K. J., Chaffin, J. A. (2001). Weight Loss, Diets, and Supplements: Does Anything Work?. Diabetes Spectr. 14: 169-175 [Full Text]  
• Ang-Lee, M. K., Moss, J., Yuan, C.-S. (2001). Herbal Medicines and Perioperative Care. JAMA 286: 208-216 [Abstract] [Full Text]  
• Margolis, M. L. (2001). A Survey of the Use of Herbal Agents Among Philadelphia Veterans Affairs Medical Center Pulmonary Outpatients. Chest 119: 1981-1982 [Full Text]  
• Hutchins, G. M., Traub, S. J., Hoyek, W., Hoffman, R. S., Haller, C. A., Benowitz, N. L. (2001). Dietary Supplements Containing Ephedra Alkaloids. NEJM 344: 1095-1097 [Full Text]  
• (2001). Some natural scepticism about the Natural Health Products Directorate. CMAJ 164: 613-613 [Full Text]  
• (2001). La Direction des produits de sante naturels : un peu de scepticisme naturel. CMAJ 164: 615-615 [Full Text]  
• (2001). Dangers of Dietary Supplements with Ephedra Alkaloids. Journal Watch Cardiology 2001: 3-3 [Full Text]  
• (2000). Risks with Phenylpropanolamine and Ephedra Alkaloids. JWatch General 2000: 1-1 [Full Text]  
• Fleming, G. A. (2000). The FDA, Regulation, and the Risk of Stroke. NEJM 343: 1886-1887 [Full Text]  
• Jordan, J., Tank, J., Shannon, J. R., Diedrich, A., Lipp, A., Schroder, C., Arnold, G., Sharma, A. M., Biaggioni, I., Robertson, D., Luft, F. C. (2002). Baroreflex Buffering and Susceptibility to Vasoactive Drugs. Circulation 105: 1459-1464 [Abstract] [Full Text]