Bitter orange is an extract from the immature green fruit of the Citrus aurantium plant. It is sometimes used in small amounts in food as a flavorant and often used in pre-workout and weight-loss supplements. The terms “bitter orange,” “bitter orange extract,” or “Citrus aurantium” are often used interchangeably with the ingredient name “synephrine.” Synephrine and octopamine are compounds found in bitter orange. Although both synephrine and octopamine occur naturally in the Citrus aurantium plant, they also can be made in a laboratory.

Although safety concerns have been raised with regard to synephrine and octopamine, the data to support these concerns are not strong. Adverse events associated with dietary supplements containing synephrine—such as fainting, chest, pain, increased heart rate, and stroke—have been reported, including at least two case reports involving Service Members. However, it cannot be concluded that synephrine directly causes such adverse events, which might be due to other ingredients in the products (such as caffeine and yohimbine) and/or the combination of synephrine with other ingredients (such as stimulants), the amount of ingredients ingested (which are not always identifiable on the label), or contamination of the products. Still, Service Members should err on the side of caution when considering whether to use supplements containing synephrine since these products often are marketed for performance enhancement and weight loss, which are considered “high-risk” supplements.

Synephrine might cause a false positive for amphetamines on urine drug screen tests. In the U.S. military drug-testing program, an initial screening (urinalysis) is done first, and if this screening test returns a positive result, then the specimen goes to confirmation analysis. Synephrine will not cause a positive result on the confirmation drug tests. Octopamine will show up if a steroid test is conducted.

The National Collegiate Athletic Association (NCAA) bans synephrine and octopamine, while the World Anti-Doping Agency (WADA) bans octopamine but not synephrine.

Updated 05 July 2017

References

Allison, D. B., Cutter, G., Poehlman, E. T., Moore, D. R., & Barnes, S. (2005). Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain? International Journal of Obesity, 29(4), 443–446. doi:10.1038/sj.ijo.0802879

Bouchard, N. C., Howland, M. A., Greller, H. A., Hoffman, R. S., & Nelson, L. S. (2005). Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine. Mayo Clinic Proceedings, 80(4), 541–545. doi:10.4065/80.4.541

Haaz, S., Fontaine, K. R., Cutter, G., Limdi, N., Perumean-Chaney, S., & Allison, D. B. (2006). Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: An update. Obesity Reviews, 7(1), 79–88. doi:10.1111/j.1467-789x.2006.00195.x

Haaz, S., Williams, K. Y., Fontaine, K. R., & Allison, D. B. (2005). Bitter orange. In P. M. Coates, J. M. Betz, M. R. Blackman, G. M. Cragg, M. Levine, J. Moss, & J. D. White (Eds.), Encyclopedia of Dietary Supplements, 2nd Edition (pp. 52–59). New York, NY: Informa Healthcare.

Jack, S., Desjarlais-Renaud, T., & Pilon, K. (2007). Bitter orange (synephrine): Update on cardiovascular reactions. Canadian Adverse Reaction Newsletter, 17(2), 2–3.

Natural Medicines. (2019). Bitter orange. Retrieved 30 April 2019 from https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=976

Stephensen, T. A., & Sarlay, R. (2009). Ventricular fibrillation associated with use of synephrine containing dietary supplement. Military Medicine, 174(12), 1313–1319. doi:10.7205/milmed-d-01-5009