Ephedra and Ephedrine for Athletic Performance Enhancement

Clinical Efficacy and Side Effects

Source Under its Evidence-based Practice Program, the Agency for Healthcare Research and Quality (AHRQ) developes scientific information for other agencies and organizations on which to base clinical guidelines, performance measures, and other quality improvement tools.

Overview AHRQ addressed research questions regarding the efficacy of herbal ephedra and ephedrine for athletic performance through a comprehensive literature review and synthesis of evidence. They assessed the safety of these products through review of clinical trials. Meta-analysis was performed where appropriate. In addition, they reviewed herbal ephedra- and ephedrine-related adverse events reports on file with the U.S. Food and Drug Administration (FDA), published case reports, and reports to a manufacturer of ephedra-containing products.

After searching published reports, journal articles, conference presentations, and various sources of unpublished studies, AHRQ identified 52 controlled clinical trials of ephedrine or herbal ephedra for weight loss or athletic performance in humans. The FDA provided copies of over 1,000 adverse event reports (AERs) related to herbal ephedra and 125 AERs related to ephedrine.

Efficacy for Physical Performance Enhancement: The effect of ephedrine on athletic performance was assessed in seven studies. No studies have assessed the effect of herbal ephedra-containing dietary supplements on athletic performance. The few studies that assessed the effect of ephedrine on athletic performance have, in general, included only small samples of fit individuals (young male military recruits) and have assessed the effects only on very short-term immediate performance. Thus, these studies did not assess ephedrine as it is used in the general population. The data support a modest effect of ephedrine plus caffeine on very short-term athletic performance. No studies have assessed the sustained use of ephedrine on performance over time. The only study that assessed the additive effects of these agents reported that ephedrine must be supplemented with caffeine to affect athletic performance.

Safety Issues: The data on adverse events were drawn from clinical trials and case reports published in the literature, submitted to the FDA, and reported to Metabolife, a manufacturer of ephedra-containing supplement products. The strongest evidence for causality should come from clinical trials; however, in most circumstances, such trials do not enroll sufficient numbers of patients to adequately assess the possibility of rare outcomes. Such was the case with our review of ephedrine and ephedra-containing dietary supplements. Even in aggregate, the clinical trials enrolled only enough patients to detect a serious adverse event rate of at least 1.0 per 1,000.

For rare outcomes, we reviewed case reports, but a causal relationship between ephedra or ephedrine use and these events cannot be assumed or proven. Evidence from controlled trials was sufficient to conclude that the use of ephedrine and/or the use of ephedra-containing dietary supplements or ephedrine plus caffeine is associated with two to three times the risk of nausea, vomiting, psychiatric symptoms such as anxiety and change in mood, autonomic hyperactivity, and palpitations. The majority of case reports are insufficiently documented to make an informed judgment about a relationship between the use of ephedrine or ephedra-containing dietary supplements and the adverse event in question. For prior consumption of ephedra-containing products, AHRQ identified two deaths, three myocardial infarctions, nine cerebrovascular accidents, three seizures, and five psychiatric cases as sentinel events; for prior consumption of ephedrine, AHRQ identified three deaths, two myocardial infarctions, two cerebrovascular accidents, one seizure, and three psychiatric cases as sentinel events. AHRQ identified 43 additional cases as possible sentinel events with prior ephedra consumption and seven additional cases as possible sentinel events for prior ephedrine consumption. About half the sentinel events occurred in persons aged 30 years or younger. Classification as a sentinel event does not imply a proven cause and effect relationship.

AHRQ did not assess the plethora of additional symptoms that have been reported in the published literature and the FDA Medwatch file for ephedra-containing dietary supplements and ephedrine products. Availability of Full Report: Printed copies may be obtained free of charge from the AHRQ Publications Clearinghouse by calling 800-358-9295. Requesters should ask for Evidence Report/Technology Assessment No. 76, Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects. The Evidence Report can also be downloaded as a zipped Word® or PDF file online at:

Questions on content or suggestions to improve this page are appreciated.

Cycling Performance Tips
Home | Table of Contents | Local Services/Information