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A Meta-analysis

Paul G. Shekelle, MD, PhD; Mary L. Hardy, MD; Sally C. Morton, PhD; Margaret Maglione, MPP; Walter A. Mojica, MD, MPH; Marika J. Suttorp, MS; Shannon L. Rhodes, MFA; Lara Jungvig, BA; James Gagné, MD

JAMA. 2003;289:1537-1545.

Context  Ephedra and ephedrine sometimes are used for weight loss or enhanced athletic performance, but the efficacy and safety of these compounds are uncertain.

Objective  To assess the efficacy and safety of ephedra and ephedrine used for weight loss and enhanced athletic performance.

Data Sources  We 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 We included unpublished trials and non–English-language documents.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 Selection  Eligible 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 Extraction  Two 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 Synthesis  No 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.

Conclusions  Ephedrine 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.

Author Affiliations: Southern California Evidence-based Practice Center–RAND, Santa Monica, Calif (Drs Shekelle, Morton, Mojica, and Mss Maglione, Suttorp, Rhodes, and Jungvig); Cedars-Sinai Medical Center, Los Angeles, Calif (Dr Hardy); Greater Los Angeles Veterans Affairs Healthcare System (Dr Shekelle); and Department of Family Medicine, University of Southern California, Los Angeles (Dr Gagné).

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