Bitter orange supplements, typically standardized to synephrine content, seem to have cardiovascular stimulant effects resulting in increased blood pressure and heart rate.[1] There have been reports of adverse reactions in at least 35 people (most commonly palpitations, fainting and dizziness) after taking a synephrine-containing supplement. The specific supplement was not recorded in all cases, but for those cases where it was, the majority of the adverse events occurred with supplements in which synephrine was combined with other active ingredients, including caffeine, deterenol (a synthetic stimulant), theophylline (a bronchodilator), beta-phenylethylamine, and yohimbine. A supplement containing synephrine with caffeine was reported in most cases of cardiovascular adverse events.[2]. Examples of these events included heart rhythm issues,[3] stroke,[4] chest pain,[5] and heart attack.[6]
Topical bitter orange products may cause irritation and increased sensitivity to the sun, increasing the risk for sunburns.[7]
Bitter orange might cause drug interactions. Some studies show that bitter orange juice increases blood levels of medications broken down by the liver enzyme called cytochrome P450 (CYP) 3A4. This seems to be due to the furanocoumarin constituents contained in certain citrus fruits.[8] Theoretically, bitter orange supplements that contain furanocoumarins can affect medications that need to be processed by the CYP3A4 enzyme in the liver.