Bitter orange (Citrus aurantium) is a small tree that bears fruit sometimes used in small amounts in food as a flavorant and often used in pre-workout and weight-loss supplements 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.

Can synephrine negatively affect my health goals?

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

Synephrine and drug testing

Synephrine (and octopamine) might register on an initial military urine screening test for amphetamines. If this happens, then the specimen goes to confirmation analysis. Synephrine (and octopamine) will not cause a positive result on the confirmation drug tests. However, octopamine will show up if a steroid test is conducted. The National Collegiate Athletic Association (NCAA) bans both synephrine and octopamine. The World Anti-Doping Agency (WADA) bans octopamine but not synephrine. FDA has advised consumers to stop using supplements containing octopamine, which is on FDA’s Dietary Supplement Ingredient Advisory List.

Updated 04 January 2021

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