title: Hemodynamic effects of ephedra-free weight-loss supplements in humans.
abstract: OBJECTIVE
  Ephedra-free weight loss dietary supplements containing bitter orange (Citrus aurantium), a botanical source of the adrenergic amines synephrine and octopamine, have quickly emerged on consumer markets to replace banned ephedra products. These supplements may have some of the health risks associated with ephedra, but studies in humans are lacking. Our aim was to characterize the pharmacokinetics and cardiovascular effects of C. aurantium dietary supplements.
  
  
  METHODS
  Ten healthy adult nonsmokers participated in a randomized, double-blind, placebo-controlled, three-arm crossover study. Single doses of C. aurantium (Advantra Z) containing 46.9 mg synephrine, Xenadrine EFX, a multi-component formulation containing 5.5 mg synephrine, and placebo were administered with a one-week washout.
  
  
  RESULTS
  Compared with placebo, Xenadrine EFX but not Advantra Z increased systolic and diastolic blood pressure with peak changes from baseline at 2 hours of 9.6 +/- 6.2 mm Hg systolic (P = 0.047), and 9.1 +/- 7.8 mm Hg diastolic (P = 0.002). Heart rate was increased from baseline at 6 hours compared with placebo (16.7 beats per minute with Xenadrine EFX, P = 0.011; 11.4 beats per minute with Advantra Z, P = 0.031). Dose-adjusted synephrine pharmacokinetics were similar between treatments with t(max) = 90 min, t(1/2) = 3.0 hours, V/F = 16347 L, and CL/F = 88.9 L/min for Xenadrine EFX.
  
  
  CONCLUSIONS
  Ephedra-free weight loss supplements have significant cardiovascular stimulant actions, similar to ephedra. These effects are not likely caused by C. aurantium alone, because an eightfold higher dose of synephrine (Advantra Z) had no effect on blood pressure, but may be attributable to caffeine and other stimulants in the multi-component formulation.
authors.affiliation: Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California, San Francisco, 94143, USA.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Haller
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
authors.forename: Peyton
authors.initials: P
authors.lastname: Jacob
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D002957:Citrus; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012016:Reference Values
chemical_list: D010936:Plant Extracts