Int J Med Sci 2012; 9(7):527-538. doi:10.7150/ijms.4446 This issue


A Review of the Human Clinical Studies Involving Citrus aurantium (Bitter Orange) Extract and its Primary Protoalkaloid p-Synephrine

Sidney J. Stohs1, Harry G. Preuss2✉, Mohd Shara3

1. Dean Emeritus, Creighton University Medical Center, Omaha, NE 68078, USA;
2. Departments of Biochemistry, Medicine and Pathology, Georgetown University Medical Center, Washington, DC 22039, USA;
3. Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.

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Stohs SJ, Preuss HG, Shara M. A Review of the Human Clinical Studies Involving Citrus aurantium (Bitter Orange) Extract and its Primary Protoalkaloid p-Synephrine. Int J Med Sci 2012; 9(7):527-538. doi:10.7150/ijms.4446. Available from

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This review summarizes the published as well as unpublished human studies involving Citrus aurantium (bitter orange) extract and its primary protoalkaloid p-synephrine, providing information and an assessment of the safety and efficacy of these widely used products. The results of over 20 studies involving a total of approximately 360 subjects that consumed p-synephrine alone or in combination with other ingredients are reviewed and critiqued. Over 50 % of the subjects involved in these studies were overweight/obese, and approximately two-thirds of these overweight/obese subjects consumed caffeine (132-528 mg/day) in conjunction with p-synephrine (10-53 mg/day). Bitter orange/p-synephrine containing products were consumed for up to 12 weeks. Approximately 44 % of the subjects consumed a bitter orange/p-synephrine only product, while the remainder consumed a complex product that contained multiple ingredients in addition to p-synephrine. In general, bitter orange extract alone (p-synephrine) or in combination with other herbal ingredients did not produce significant adverse events as an increase in heart rate or blood pressure, or alter electrocardiographic data, serum chemistry, blood cell counts or urinalysis. p-Synephrine alone as well as in combination products were shown to increase resting metabolic rate and energy expenditure, and modest increases in weight loss were observed with bitter orange extract/p-synephrine-containing products when given for six to 12 weeks. Longer term studies are needed to further assess the efficacy of these products and affirm their safety under these conditions.

Keywords: Citrus aurantium, bitter orange, p-synephrine, human subjects, obesity/overweight, safety, efficacy, caffeine.