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A Randomized Controlled Trial

Brian F. McBride, PharmD; Angeliki K. Karapanos, BSPharm; Agnes Krudysz, BSN, BSPharm; Jeffrey Kluger, MD; Craig I. Coleman, PharmD; C. Michael White, PharmD

JAMA. 2004;291:216-221.

Context  Metabolife 356, a multicomponent dietary supplement containing ephedra and caffeine (DSEC) in addition to several other components, is the top-selling dietary weight loss supplement. Given its common use, anecdotal reports of cardiovascular and cerebrovascular adverse events, and paucity of safety data, further research with this DSEC was warranted.

Objective  To determine the impact of the DSEC on corrected QT (QTc) interval duration and systolic blood pressure (SBP).

Design  Randomized, double-blind, placebo-controlled, crossover study conducted from January to May 2003.

Setting and Participants  Fifteen healthy volunteers (mean [SD] age, 26.7 [2.52] years; weight, 72.7 [14.93] kg), 6 (40%) of whom were women, recruited from the University of Connecticut, Storrs campus.

Intervention  A single dose of the DSEC (containing 19 ingredients including ephedra [12 mg] and caffeine [40 mg]) or matching placebo were administered in a crossover fashion with a 7-day washout period between treatments.

Main Outcome Measures  Maximal QTc interval and SBP assessed at 1, 3, and 5 hours after dosing for the DSEC relative to placebo.

Results  Individuals receiving the DSEC had a longer maximal QTc interval (mean [SD], 419.4 [11.8] vs 396.1 [15.7] milliseconds; P<.001) and higher SBP (mean [SD], 123.5 [10.98] vs 118.93 [9.62] mm Hg; P = .009) compared with placebo. Participants who received the DSEC were more likely to experience a QTc interval increase of at least 30 milliseconds vs placebo (8 individuals [53.3%] vs 1 individual [6.7%]; relative risk, 2.67 [95% confidence interval, 1.40-5.10]). There were no significant sex-related differences.

Conclusions  The ephedra- and caffeine-containing dietary supplement Metabolife 356 increased the mean maximal QTc interval and SBP. Since the actual ingredient or ingredients in Metabolife 356 responsible for these findings are not known, patients should be instructed to avoid this and similar dietary supplements until more information is known about their safety.

Author Affiliations: University of Connecticut Schools of Pharmacy (Drs White, Kluger, Coleman, and McBride, and Mss Karapanos and Krudysz) and Medicine (Dr Kluger), Storrs and Farmington, Conn; and Divisions of Cardiology (Drs Kluger and White) and Drug Information (Drs McBride, Coleman, and White), Hartford Hospital, Hartford, Conn.

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