Efficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic Performance

Abstract

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 We included unpublished trials and non–English-language documents.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.

Effects of Ephedrine-Containing Products on Weight Loss and Lipid Profiles: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…However, 1 year later, the U.S. District Court overturned the FDA's ban [39], and the cardiovascular safety of ephedrine remained to be clarified. Our meta-analysis results show that patients taking ephedrine-containing products had faster heart rates, which was consistent with previous studies showing that ephedrine-containing dietary supplements were associated with a 2-fold higher risk of palpitations [20]. However, our review failed to demonstrate statistical significance in terms of ephedrine's effects on SBP and DBP, possibly due to the small number of included studies.…”

Effect of a Dietary Herbal Supplement Containing Caffeine and Ephedra on Weight, Metabolic Rate, and Body Composition*

“…The only adverse event in this trial that could logically be attributed to catacholamines, arrhythmia, was seen in the placebo group. The lack of toxicity in this trial is consistent with other trials of C&E in both herbal and pharmaceutical forms (4,21) Phase III gives further evidence of safety. There was no evidence from physical examination, electrocardiogram, blood tests, or urinalysis of toxicity from a 6‐month course of treatment with the herbal dietary supplement containing C&E.…”

Psychiatric Effects of Ephedra Use: An Analysis of Food and Drug Administration Reports of Adverse Events

“…In 2003, the FDA proposed placing a telephone number on product labels for reporting adverse events; since then, a ban on ephedra dietary supplements has taken effect. Our findings are another piece of evidence in addition to evidence of minor psychiatric symptoms found in randomized clinical trials (7). Although firm conclusions regarding the severe psychiatric effects of ephedra have not been established, taken together, these pieces of evidence raise concern that ephedra may be related to such symptoms.…”