ContextEphedra and ephedrine sometimes are used for weight loss or enhanced athletic performance, but the efficacy and safety of these compounds are uncertain.ObjectiveTo assess the efficacy and safety of ephedra and ephedrine used for weight loss and enhanced athletic performance.Data SourcesWe searched 9 databases using the terms ephedra, ephedrine, adverse effect, side effect, efficacy, effective, and toxic. We included unpublished trials and non–English-language documents. Adverse events reported to the US Food and Drug Administration MedWatch program were assessed.Study SelectionEligible studies were controlled trials of ephedra or ephedrine used for weight loss or athletic performance and case reports of adverse events associated with such use. Eligible studies for weight loss were human studies with at least 8 weeks of follow-up; and for athletic performance, those having no minimum follow-up. Eligible case reports documented that ephedra or ephedrine was consumed within 24 hours prior to an adverse event or that ephedrine or an associated product was found in blood or urine, and that other potential causes had been excluded. Of the 530 articles screened, 52 controlled trials and 65 case reports were included in the adverse events analysis. Of more than 18 000 other case reports screened, 284 underwent detailed review.Data ExtractionTwo reviewers independently identified trials of efficacy and safety of ephedra and ephedrine on weight loss or athletic performance; disagreements were resolved by consensus. Case reports were reviewed with explicit and implicit methods.Data SynthesisNo weight loss trials assessed duration of treatment greater than 6 months. Pooled results for trials comparing placebo with ephedrine (n = 5), ephedrine and caffeine (n = 12), ephedra (n = 1), and ephedra and herbs containing caffeine (n = 4) yielded estimates of weight loss (more than placebo) of 0.6 (95% confidence interval, 0.2-1.0), 1.0 (0.7-1.3), 0.8 (0.4-1.2), and 1.0 (0.6-1.3) kg/mo, respectively. Sensitivity analyses did not substantially alter the latter 3 results. No trials of ephedra and athletic performance were found; 7 trials of ephedrine were too heterogeneous to synthesize. Safety data from 50 trials yielded estimates of 2.2- to 3.6-fold increases in odds of psychiatric, autonomic, or gastrointestinal symptoms, and heart palpitations. Data are insufficient to draw conclusions about adverse events occurring at a rate less than 1.0 per thousand. The majority of case reports are insufficiently documented to allow meaningful assessment.ConclusionsEphedrine and ephedra promote modest short-term weight loss (≈0.9 kg/mo more than placebo) in clinical trials. There are no data regarding long-term weight loss, and evidence to support use of ephedra for athletic performance is insufficient. Use of ephedra or ephedrine and caffeine is associated with increased risk of psychiatric, autonomic, or gastrointestinal symptoms, and heart palpitations.

There is good evidence that vitamin E supplementation does not beneficially or adversely affect cardiovascular outcomes.

containing products to promote weight loss or to enhance athletic performance has garnered a great deal of recent attention, due in part to a number of wellpublicized adverse events reportedly associated with the use of ephedra-or ephedrine alkaloid-containing products. [1][2][3] These reports have led several groups to ask the US Food and Drug Administration (FDA) to ban the production and sale of ephedra products. 4 Advocates counter that ephedra is safe and effective. 5 The US Department of Health and Human Services requested this synthesis of available evidence regarding efficacy and safety of ephedra use to clarify the existing state of the science on ephedrine alkaloids. The National Institutes of Health will use this information to guide an expanded research effort to better understand the safety of ephedrine alkaloids. 6

Clinicians should be aware that serious psychiatric symptoms could be associated with ephedra use.