Send to

Choose Destination
Phytother Res. 2016 May;30(5):842-7. doi: 10.1002/ptr.5590. Epub 2016 Mar 7.

Cardiovascular Safety of Oral p-Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo-Controlled Cross-over Clinical Trial.

Author information

Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
Dean Emeritus, Creighton University Medical Center, Omaha, NE, 68178, USA.


Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p-synephrine are widely consumed in combination with multiple herbal ingredients for weight management and sports performance. p-Synephrine is also present in juices and foods derived from a variety of Citrus species. Questions exist regarding the safety of p-synephrine because of structural similarities with other biogenic amines. This study assessed the cardiovascular (stimulatory) effects of bitter orange extract (49-mg p-synephrine) given to 18 healthy subjects (nine men and nine women) in a double-blinded, placebo-controlled cross-over study. Heart rates, blood pressures, and electrocardiograms were determined at baseline, 30, 60, 90 min, 2, 4 , 6, and 8 h. Blood samples were drawn at baseline, 2 h and 8 h for serum chemistries, blood cell counts, and p-synephrine and caffeine levels. No significant changes occurred in electrocardiograms, heart rates, systolic blood pressure, blood chemistries, or blood cell counts at any time point in either control or p-synephrine treated group. A small (4.5 mmHg) decrease in diastolic blood pressure occurred in the p-synephrine treated group at 60 min. No adverse effects were reported. Caffeine ingestion varied markedly among the participants. p-Synephrine does not act as a stimulant at the dose used.


Citrus aurantium; ECG; bitter orange; blood chemistry; blood pressure; heart rate; hemodynamic effects; p-synephrine

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center