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.
What is bitter orange?
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.
What are bitter orange’s main benefits?
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.
What are bitter orange’s main drawbacks?
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.
How does bitter orange work?
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]
What are other names for Bitter orange?
Note that Bitter orange is also known as:
- Bitter Orange
- P-synephrine
- Citrus Aurantium
- Synephrine
Bitter orange should not be confused with:
Dosage information
A recommended dosage is 10-20mg, taken thrice a day.
Acute dosages of 50mg are also frequently used, although not thrice a day.
Frequently asked questions
The National Collegiate Athletic Association (NCAA) lists synephrine (bitter orange) as a banned stimulant. One small study found that taking 100 mg of synephrine slightly enhanced muscle endurance during resistance exercise compared to control.[13]
A longer-duration study found that 4 weeks of daily administration of a supplement containing 20 mg synephrine improved some areas of exercise performance, but after 8 weeks no clear differences compared to the supplement without synephrine were noted.[4]
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.
Limited research did not find a benefit. An analysis of 3 small studies found that taking 10–54 mg of synephrine daily for 6–8 weeks had no significant effects on weight loss or fat mass.[3]
Limited research suggests that bitter orange supplements may increase fat oxidation during exercise and affect resting metabolic rate. One small study of 14 healthy adults found that taking a single dose of p-synephrine prior to one hour of cycling exercise, at a dosage of 3 mg of synephrine per kg of body weight (3 mg/kg), increased the amount of fat burned and decreased the amount of carbohydrates utilized, but did not affect total energy expenditure compared to placebo.[14]. Another small study found that 10 individuals given 50 mg of synephrine had a 65 kcal increase in their resting metabolic rate compared to placebo, but this result was not significant.[15]
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.
Some limited research suggests that bitter orange supplements may increase blood pressure, while other research found no effect. A meta-analysis of small randomized controlled studies suggests that taking bitter orange extract alone or with other ingredients for 56–60 days increases systolic blood pressure by up to 6.4 mmHg compared to control; however, there was no significant effect on diastolic blood pressure. Acute administration of bitter orange extract tended to increase blood pressure over 3 hours, but this result was not statistically significant.[3] One randomized crossover trial of 15 healthy, young adults given a single dose of bitter orange supplement containing 108 mg of synephrine, which was included in the above meta-analysis, reported that the participants given synephrine experienced modestly increased blood pressure and heart rate for up to 5 hours compared to placebo.[16] In another small study, in which participants were given a single, smaller dose of 27 mg of synephrine and monitored for 8 hours, no significant difference from placebo was seen on t blood pressure or electrocardiogram (QT interval).[17] In a small study of healthy young adults sitting quietly for 3 hours after taking a single dose of 103 mg p-synephrine, alone or with 240 mg caffeine, blood pressure and heart rate were not affected compared to placebo.[18] These results suggest that caffeine and synephrine may not always have synergistic effects in the short term.
A small study of 10 healthy adults considered 2 different dietary supplements containing synephrine and compared heart rate and blood pressure results with placebo after a single dose (Advantra Z, containing 46.9 mg synephrine, and Xenadrine EFX, containing 5.5 mg synephrine). Interestingly, the Xenadrine EFX group experienced more blood pressure and heart rate elevations than the Advantra group, possibly due to other ingredients in the supplement.[19]
The longer-term effects of a 20 mg daily dose of synephrine were examined in an 8 week study of healthy, young, resistance-trained males; researchers found no changes in blood pressure or heart rate compared to control.[4].
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]
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