Blood pressure and heart rate effects following a single dose of bitter orange

Ann Pharmacother. 2006 Jan;40(1):53-7. doi: 10.1345/aph.1G488. Epub 2005 Nov 29.


Background: The ingredients of numerous "ephedra-free" dietary supplements used for weight loss include bitter orange, which contains sympathomimetic alkaloids such as synephrine. Due to the similarity in chemical structure to ephedrine and the potential sympathomimetic effects of synephrine, it is hypothesized that bitter orange may increase blood pressure (BP) and heart rate (HR).

Objective: To determine the effects on BP and HR after a single dose of bitter orange in healthy adults.

Methods: In a prospective, randomized, double-blind, placebo-controlled, crossover study, 15 young, healthy, adult subjects received either a single dose of Nature's Way Bitter Orange--a 900 mg dietary supplement extract standardized to 6% synephrine--or matching placebo, with a one week washout period. Systolic BP (SBP), diastolic BP (DBP), and HR were measured at baseline and every hour for 6 hours after administration.

Results: SBP after bitter orange was significantly increased versus placebo at hours 1-5 (p < 0.0001); the peak difference was 7.3 +/- 4.6 mm Hg. Although the baseline DBP was higher than after administration of both placebo and bitter orange, DBP after bitter orange was significantly increased versus placebo at hours 4 and 5 (p < or = 0.02); the peak difference was 2.6 +/- 3.8 mm Hg. HR was significantly increased after bitter orange versus placebo for hours 2-5 (p < 0.01); the peak difference was 4.2 +/- 4.5 beats/min.

Conclusions: SBP, DBP, and HR were higher for up to 5 hours after a single dose of bitter orange versus placebo in young, healthy adults.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Pressure / drug effects*
  • Body Mass Index
  • Citrus aurantiifolia / chemistry*
  • Cross-Over Studies
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Heart Rate / drug effects*
  • Humans
  • Male
  • Placebos
  • Plant Extracts / administration & dosage
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Prospective Studies
  • Time Factors


  • Placebos
  • Plant Extracts