Bitter orange, also known as Citrus aurantium, is a citrus fruit originally used in Traditional Chinese medicine for stomach ailments, such as constipation, diarrhea, and indigestion.^[1] Today, bitter orange extract, standardized to p-synephrine content, commonly occurs in multi-ingredient formulations labeled as ephedra-free supplements for weight loss: p-synephrine is an alkaloid compound structurally similar to adrenaline and the banned dietary supplement ephedrine.^[2] The pharmacologic and pharmacokinetic properties of p-synephrine vary from its structural analogues enough to mitigate the risks previously seen with ephedrine-containing supplements. ^[1]. p-synephrine should also not be confused with m-synephrine, a synthetic amine derivative of synephrine. m-synephrine does not meet the FDA dietary supplement definition and is a prohibited ingredient.

There is interest in using bitter orange for weight loss and improvement in body composition (fat loss). However, this is not supported by clinical data.^[3] Bitter orange is also used for athletic performance, but its benefit is not clear.^[4]

One study found that applying bitter orange oil 20–25% to affected skin for 1 to 3 weeks was associated with cure of fungal infections like ringworm, jock itch, or athlete’s foot.^[5] However, that study was limited by a lack of control group.

Bitter orange supplements, typically standardized to synephrine content, seem to have cardiovascular stimulant effects resulting in increased blood pressure and heart rate.^[3] 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.^[6]. Examples of these events included heart rhythm issues,^[7] stroke,^[8] chest pain,^[9] and heart attack.^[10]

Topical bitter orange products may cause irritation and increased sensitivity to the sun, increasing the risk for sunburns.^[11]

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.^[12] Theoretically, bitter orange supplements that contain furanocoumarins can affect medications that need to be processed by the CYP3A4 enzyme in the liver.

The synephrine in bitter oranges is thought to work as a sympathetic adrenergic agonist, stimulating receptors involved in the “fight or flight” response. These effects stimulate the cardiovascular system resulting in increased heart rate and blood pressure. Also, these effects may stimulate metabolism, resting metabolic rate and lipolysis (breakdown of fat). Appetite may also be suppressed via slowed movement of food through the gastrointestinal tract.^{[2] [6]}