title: Cardiovascular Safety of Oral p-Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo-Controlled Cross-over Clinical Trial.
abstract: 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. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
authors.forename: Mohd
authors.initials: M
authors.lastname: Shara
authors.affiliation: Dean Emeritus, Creighton University Medical Center, Omaha, NE, 68178, USA.
authors.forename: Sidney J
authors.initials: SJ
authors.lastname: Stohs
authors.affiliation: Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
authors.forename: Tareq L
authors.initials: TL
authors.lastname: Mukattash
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D002957:Citrus / Q000737:chemistry*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology; D011446:Prospective Studies; D013578:Synephrine / Q000737:chemistry* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D010936:Plant Extracts; D013578:Synephrine
keywords: Citrus aurantium; ECG; bitter orange; blood chemistry; blood pressure; heart rate; hemodynamic effects; p-synephrine