Ephedrine alkaloid products, used to enhance weight loss and improve athletic performance, recently have come under scrutiny because of well-publicized adverse effects. Shekelle and colleagues searched nine databases for studies on weight loss, athletic performance, and adverse effects.

Weight loss trials were required to be at least eight weeks in duration. When possible, data were pooled for clinically similar trials. Because of the low statistical power of even the aggregate clinical trials, the authors also searched for case reports to establish the potential for causal relationships between adverse events and ephedrine products.

The authors identified five trials comparing ephedrine with placebo. The random-effects pooled estimate of the weight loss rate was 1.3 lb (0.6 kg) per month above weight loss with placebo. Of 12 trials comparing ephedrine and caffeine with placebo, the random-effects pooled estimate of the weight loss rate was 2.2 lb (1.0 kg) per month above weight loss with placebo. The pooled average percentage weight loss was 11 percent at four months. Other studies comparing ephedra with placebo or herbs containing caffeine yielded similar results.

Six trials that measured athletic performance reported no improvements using caffeine or ephedrine; when used in combination, exercise performance improved in terms of oxygen consumption, time to exhaustion, and carbohydrate consumption.

In 50 trials assessing the safety of ephedra, participants in active treatment had 2.2 to 3.6 increased odds of psychiatric symptoms, autonomic hyperactivity, upper gastrointestinal symptoms, and heart palpitations. Data were too sparse to determine dosage effects and the effects of adding caffeine. Published case reports did not contain sufficient data to make an informed judgment about adverse events. In unpublished reports, two deaths, three myocardial infarctions, nine cerebrovascular accidents, three seizures, and five psychiatric cases were associated with prior ephedra intake; similar numbers were associated with ephedrine.

The authors determined that evidence supports the efficacy of ephedra- and ephedrine-related products in promoting modest weight loss, at least in the short term, and that caffeine enhances this efficacy. Athletic performance trials were not controlled and not representative of general repeated use, so they did not lead to definitive conclusions about whether ephedrine products enhance athletic performance. Ephedrine and ephedra products are associated with a twofold to threefold risk of psychiatric symptoms, autonomic symptoms, upper gastrointestinal symptoms, and heart palpitations; caffeine may contribute to these effects. More serious adverse effects cannot be excluded, but if they occur, they are uncommon.