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

Objective: To synthesize the evidence for the safety and efficacy of ephedra for weight loss and athletic performance. Data sources: Using the terms ephedra, ephedrine, adverse effect, side effect, efficacy, effective, and toxic, 9 databases including MEDLINE, AMED, and International Pharmaceutical Abstracts were searched up to 2001 for controlled trials reported in any language that assessed weight loss or athletic performance in humans. The reference lists of retrieved articles were searched, and unpublished evidence was solicited. Case reports from FDA MedWatch files, published literature, and symptom reports to a manufacturer of dietary supplements were screened. Study selection: For pooled analysis of efficacy of ephedrine products for weight loss, trials were required to have an 8-week treatment duration and have a placebo comparison group (n = 19). The 8 controlled studies of ephedrine to enhance performance were selected despite diverse performance measures. Studies selected for assessing adverse effects were 52 controlled trials and 65 case reports (independently selected from 530 articles and reports by 2 reviewers). Adverse events reports that documented that ephedra or ephedrine was consumed 24 hours before the event, or that identified ephedra use in blood or urine tests, and that had no plausible alternative explanation for the adverse event were included. Data extraction: Details of study methods, type of intervention, trial duration, sample size, and outcomes were extracted. Adverse events were divided into 7 categories. Main results: Ephedrine was more effective than placebo in promoting weight loss: ephedrine versus placebo (6 comparisons), random effects pooled estimate of greater weight loss, 0.6 kg/mo (95% CI, 0.2–1.0); and ephedrine and caffeine versus placebo (12 trials), estimate of greater weight loss, 1.0 kg/mo (CI, 0.7–1.3). Ephedra alone (1 trial) and ephedra with herbs containing caffeine (4 trials) were similarly more effective than placebo in promoting weight loss. In 6 crossover trials by the same investigators, exercise capacity in young men (oxygen consumption, time to exhaustion, or carbon dioxide production) was not improved by a single dose of ephedrine or caffeine alone, but the combination resulted in a 20% to 30% increase in performance. Compared with side effects from placebo, ephedrine and ephedra (with or without caffeine) were associated with raised pooled odds ratios for psychiatric symptoms (3.64; 95% CI, 1.91–7.31), autonomic hyperactivity (3.37; CI, 2.19–5.31), heart palpitations (2.29; CI, 0.49–13.34), upper gastrointestinal tract symptoms (2.15; CI, 1.39– 3.38), and headache (1.64; CI, 0.62– 4.68). Tachycardia was reported in 6 instances in the intervention groups and none in the placebo groups. These side effects were not deemed severe. Among the 17,842 adverse event reports, 5 deaths, 5 myocardial infarctions, 11 cerebrovascular accidents, 4 seizures, and 8 psychiatric cases were attributed to consumption of ephedra or ephedrine. A further 50 similar events were possibly associated with ephedra or ephedrine consumption. About half of the serious adverse events occurred in persons younger than 30 years. Conclusions: Ephedrine and ephedra resulted in a small improvement in weight loss, but with an excess of side effects. There was insufficient evidence to evaluate ephedrine and ephedra as athletic performance enhancers. In case reports, ephedra or ephedrine consumption was probably or possibly related to serious adverse events.