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 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, 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.

The U.S. Food & Drug Administration (FDA) recently determined octopamine to be a new dietary ingredient (NDI) for which an NDI notification is required and has not yet been submitted. Therefore, any product containing octopamine is considered “adulterated.” For this reason, octopamine is on the DoD Prohibited Dietary Supplement Ingredients list, so Service Members should avoid products that contain this ingredient.


Updated 10 May 2022


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