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).
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 We included unpublished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
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
Shekelle PG, Hardy ML, Morton SC, Maglione M, Mojica WA, Suttorp MJ, Rhodes SL, Jungvig L, Gagné J. Efficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic PerformanceA Meta-analysis. JAMA. 2003;289(12):1537–1545. doi:10.1001/jama.289.12.1470