Short‐term Metabolic and Hemodynamic Effects of Ephedra and Guarana Combinations

Objective Serious adverse health events have been reported with the use of dietary supplements containing ephedra and guarana. We sought to determine whether repeated dosing and multi‐ingredient formulations contribute to the adverse effects of these supplements. Methods In this study, 16 healthy adults (8 women) took 2 doses each of ephedra‐guarana alone, Xenadrine RFA, a multicomponent dietary supplement containing 25 mg ephedra alkaloids and 200 mg caffeine, or placebo 5 hours apart in a randomized, double‐blind, 3‐arm crossover study. Results Peak plasma ephedrine levels averaged 130 to 140 ng/mL. Compared with placebo, Xenadrine and ephedra‐guarana significantly increased heart rate (maximum increase, 9.4 ± 8.6 beats/min; P = .002), blood pressure (maximum increase in systolic and diastolic pressure, 11.5 ± 10.7 mm Hg and 7.3 ± 7.4 mm Hg, respectively; P = .015), postprandial glucose concentration (maximum change, 41.0 ± 18.8 mg/dL; P < .0001), and insulin concentration (maximum change, 41.2 ± 47.8 μIU/mL; P = .005). Serum potassium concentrations were significantly decreased by both treatments. Hemodynamic and metabolic changes were observed after both the first and second doses. However, plasma free fatty acid concentrations increased after the first dose only. Xenadrine RFA produced higher increases in glucose concentration than ephedra‐guarana, but no other pharmacodynamic differences between the treatments were found. Conclusions Consumption of 2 doses of ephedra and guarana supplements, per supplement label recommendations, results in persistent increases in heart rate and blood pressure and unfavorable actions on glucose and potassium homeostasis. Such effects could be detrimental in persons with hypertension, atherosclerosis, or glucose intolerance, conditions that are strongly associated with obesity. Clinical Pharmacology & Therapeutics (2005) 77 , 560–571; doi: 10.1016/j.clpt.2005.01.023