Bitter Orange (Synephrine)

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HPRC Dietary Supplement Classification System: Bitter Orange (Synephrine)


Bitter Orange (Synephrine)

Citrus aurantium is the botanical name for a plant commonly referred to as bitter orange, sour orange, Neroli, Chongcao, and Seville orange. It is a source of synephrine and several other biogenic amines (certain organic compounds), as well as other bioactive phytochemicals (i.e., chemicals naturally produced by plants). It is used in dietary supplements for weight loss as an alternative to ephedrine alkaloids contained in the ephedra plant (see monograph in this series).1,2 Bitter orange extracts commonly contain from 1.5% to 6% synephrine.3 There are six different isomers of synephrine, and it is unclear which isomers are present in bitter orange products.3,4 Bitter orange has been used in and by indigenous people of the Amazon rainforest for nausea, indigestion, and constipation.3 Current popular uses of bitter orange are for heartburn, loss of appetite, nasal congestion, and weight loss. It is also applied to the skin for fungal infections such as ringworm and athlete’s foot.3

Dose Range and Upper Limit

Bitter Orange (Synephrine)

Food and Nutrition Board DRI:

RDA/AI: Not relevant for this substance.

Upper Limit: Not relevant for this substance.

Doses Used In Randomized Clinical Trials: Synephrine has been evaluated in small clinical studies, usually in combination with other active ingredients. Some common supplements on the market recommend 120 mg/day of synephrine alkaloids (extracted from Citrus aurantium) for weight loss.1 P-synephrine (phenylephrine, one of the most common forms of synephrine) has been used clinically at 300 mg/day.3

Toxicology Data: 1000 mg/day of bitter orange is the minimum adult lethal dose.1

Benefits and Risks

Bitter Orange (Synephrine)

Evaluation of Potential Benefits

There is contradictory evidence about the effects of bitter orange on weight. Some preliminary clinical research suggests that a combination of bitter orange, caffeine, and St. John’s Wort might help weight reduction when used with caloric restriction and exercise. However, other preliminary clinical research suggests that a different specific combination product (Labrada’s “Charge”)—which contains 150 mg bitter orange and provides 9 mg synephrine, plus caffeine and several other ingredients—taken twice daily does not significantly reduce weight.3 There is no known optimal dose for synephrine to promote weight loss, and it is not known if bitter orange is effective for weight loss.3,5

Potential Detrimental Effects on…

Military Performance: Taking a single 900 mg dose of bitter orange standardized to 6% synephrine (54 mg) seems to increase diastolic and systolic blood pressure and heart rate for up to five hours in young, healthy adults and can cause headaches.3

Military Survivability: People should avoid taking bitter orange supplements if they have a heart condition or high blood pressure.3 There are case reports of stroke, tachy- or ventricular arrhythmia (dangerously fast and/or irregular heart rate), cardiac arrest, syncope (loss of consciousness), angina (heart-related chest pain), myocardial infarction (“heart attack”), and death in otherwise healthy patients who have taken bitter orange extract alone or in combination with other stimulants such as caffeine.2,3,5 A specific case of an otherwise healthy, 27-year-old active duty female Airman reported ventricular fibrillation in conjunction with the use of a dietary supplement containing synephrine.5 Health Canada has received 16 reports of adverse cardiovascular reactions to bitter orange or synephrine, including tachycardia, syncope, ventricular fibrillation, and cardiac arrest.5

Other Health Risks

In addition to cardiovascular effects, there are potential adverse reactions in people with central-nervous-system disorders, thyroid disorders, pheochromocytoma (a tumor of the adrenal gland that affects heart rate and blood pressure), or enlarged prostate.2,3

Interactions with Medications or Other Bioactive Substances

People should avoid taking bitter orange supplements if they are taking medications such as MAO inhibitors. Potential risk of cardiotoxicity when consumed with dextromethorphan (Robitussin DM and others), Feledopine (blood pressure), drugs with central nervous system stimulant properties (phenylpropanolamine, pseudoephedrine, and caffeine),3 and stimulant herbs that speed up the heart rate, such as ephedra and caffeine. Caffeine-containing supplements such as coffee, cola nut, guarana, and mate seem to increase the risk of hypertension and adverse cardiovascular effects.3

For details of these and other potential interactions, visit the Natural Medicines Comprehensive Database.3

Withdrawal Effects

No data found.

Concern and Benefit Estimate (see Dietary Supplement Risk Matrix)

Benefit potential: Low
Risk (safety concern): High
Classification score: 12

Synephrine is used largely as a substitute in weight loss supplements for the now-banned ephedra, but there is little evidence of its effectiveness. Possible detrimental effects are primarily heart-related and potentially fatal.


Bitter Orange (Synephrine)

  1. Haaz S, Williams KY, Fontaine KR, Allison DB. Bitter orange. In: Coates PM, Betz JM, Blackman MR, et al., eds. Encyclopedia of Dietary Supplements. 2nd ed. New York: Informa Healthcare; 2010:52-29.
  2. Health Canada. Bitter orange (synephrine):update on cardiovascular reactions. Canadian Adverse Reaction Newsletter. 2007;17(2).
  3. Jellin J, Gregory, PJ, eds. Bitter orange. Natural Medicines Comprehensive Database 2010;
  4. Haaz S, Fontaine KR, Cutter G, Limdi N, et al. Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update. Obes. Rev. 2006;7(1):79-88.
  5. Stephensen TA, Sarlay R. Ventricular Fibrillation Associated With Use of Synephrine Containing Dietary Supplement. Milit. Med. 2009;174(12):1313-9.