A 60day double-blind, placebo-controlled safety study involving Citrus aurantium (bitter orange) extract

Food Chem Toxicol. 2013 May;55:358-62. doi: 10.1016/j.fct.2013.01.013. Epub 2013 Jan 25.


Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p-synephrine are widely consumed in dietary supplements for weight management and sports performance. p-Synephrine is also present in foods derived from a variety of Citrus species. Bitter orange extract is commonly used in combination with multiple herbal ingredients. Most clinical studies conducted on bitter orange extract alone have involved single doses. The purpose of this study was to assess the safety of bitter orange extract (approximately 49mg p-synephrine) alone or in combination with naringin and hesperidin twice daily given to 25 healthy subjects per group for 60days in a double-blinded, placebo-controlled protocol. No significant changes occurred in systolic or diastolic blood pressures, blood chemistries or blood cell counts in control or p-synephrine treated groups. Small, clinically insignificant differences in heart rates were observed between the p-synephrine plus naringin and hesperidin group and the p-synephrine alone as well as the placebo group. No adverse effects were reported in the three groups. Bitter orange extract and p-synephrine appear to be without adverse effects at a dose of up to 98mg daily for 60days based on the parameters measured.

MeSH terms

  • Adult
  • Aged
  • Citrus / chemistry*
  • Double-Blind Method
  • Humans
  • Middle Aged
  • Placebos
  • Plant Extracts / adverse effects
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use


  • Placebos
  • Plant Extracts