Ephedra and Caffeine’s Impact on Heart Rate and Systolic Blood Pressure

McBride B, Karapanos A, Krudysz A, et al. Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine JAMA. 2004;291(2):216-221.

Dietary weight-loss supplements often contain both ephedra and caffeine along with other natural ingredients. Anecdotal cases of sudden cardiac death and cerebrovascular adverse events associated with the combination of ephedra and caffeine have been reported. Consumers consider the herbal preparations as safe; however, safety data is lacking. Metabolife 356® (Metabolife International Inc, San Diego, CA) was one of the top selling dietary supplement containing ephedra and caffeine. It also contained a variety of ingredients, such as eleuthero (a.k.a. Siberian ginseng; Eleutherococcus senticosus), ginger (Zingiber officinale), and goldenseal (Hydrastis canadensis) in proprietary amounts.

An electrocardiogram (abbreviated as ECG or EKG) can be used to record the electrical activity of the heart during contraction. Waves (labeled as P, Q, R, S, T, and U) are generated on paper showing the activity of the atria and ventricles of the heart. The QT interval shows the excitation and relaxation of the ventricles. This study evaluated the impact of ephedra plus caffeine on the corrected QT (QTc) interval and on systolic blood pressure.

Fifteen healthy men and women participated in this randomized, double-blind, placebo-controlled, crossover study. Participants received either 1 capsule of Metabolife 356 or placebo. This was followed by a 7-day washout period after which they received the opposite treatment. Hemodynamic and electrocardiographic variables were evaluated immediately before and after ingestion of the capsules.

After dosing, the maximum QTc interval was 5.9% higher with Metabolife 356 than with placebo (P<0.001). The average QTc interval increased from baseline by 27.20 milliseconds when Metabolife 356 was consumed compared to 2.63 milliseconds when placebo was consumed (P=0.03). Fifty-three percent of the participants had QTc interval increases of at least 30 seconds while taking Metabolife 356. The QTc interval was greater in the Metabolife 356 group for every time point. The Metabolife group also had a higher post-dosing systolic blood pressure at 5 hours (P = 0.009). All patients receiving Metabolife 356 reported nonspecific adverse events, such as jitteriness, queasiness, or 'not feeling quite right.' No adverse events were reported while participants were taking placebo. One participant developed tachycardia (increased heart rate), one developed a hand tremor, and another developed premature ventricular complexes while taking Metabolife 356. The European Center for Proprietary Medicinal Products recognizes a drug induced increase in the QTc interval of at least 30 milliseconds as a potential cause of concern for developing ventricular tachycardia. Ventricular tachycardia is a potentially unstable rhythm that may result in fainting, low blood pressure, shock, or sudden death. The FDA has no official standards regarding products and ventricular tachycardia. However, the drugs cisapride and terfenadine were removed from the U.S. market due to cases of prolonged QTc intervals in the range of 13 to 17 milliseconds. Overall, this study showed that a single dose of a dietary supplement containing ephedra and caffeine significantly prolongs the QTc interval, which is a risk factor for developing heart arrhythmias (abnormal heart rhythm). The supplement also increased systolic blood pressure. The authors conclude that Metabolife 356 and other products with similar ingredients should be avoided until more information is known. —Heather S. Oliff, Ph.D American Botanical Council, 6200 Manor Rd, Austin, TX 78723