Absence of QTc-interval-prolonging or hemodynamic effects of a single dose of bitter-orange extract in healthy subjects

Study Objective. To evaluate the hemodynamic and electrocardiographic effects of a single dose of commercially available bitter-orange dried-fruit extract, which is increasingly being used in dietary supplements. Design. Randomized, double-blind, placebo-controlled, crossover study. Setting. University of Connecticut, Storrs Campus. Subjects. Eighteen healthy volunteers aged 18 years or older. Intervention. Subjects were given either placebo or bitter-orange dried-fruit extract (450 mg standardized to 27 mg of m- or p-synephrine) in phase 1. The opposite treatment was given during phase 2 after a washout period of at least 7 days. Measurements and Main Results. The rate-corrected QT (QTc) interval and blood pressure were measured before dosing and at 1, 3, 5, and 8 hours after dosing. Mean ± SD values of the maximum postdose values were compared between groups. Subjects receiving bitter-orange extract versus those receiving placebo had similar postdose QTc intervals (402 ± 29 vs 403 ± 24 msec, p=0.653), systolic blood pressure (114 ± 10 vs 115 ± 8 mm Hg, p=0.686) and diastolic blood pressure (68 ± 9 vs 68 ± 8, p=0.879). Conclusion. Bitter-orange dried-fruit extract standardized to m- or p-synephrine 27 mg did not significantly alter the QTc interval or blood pressure after a single dose was administered. Future studies are necessary to ensure the safety of this herbal product with multiple doses.