Citrus aurantium is the Latin name for a fruit called Seville orange, or bitter orange. The juice, peel, and essential oil have all been used medicinally. Traditionally uses include digestive problems, epilepsy, fatigue, insomnia, infections, respiratory problems, skin problems, and many other uses. As a flavoring, essence of bitter orange is found in the drinks Triple Sec and Cointreau.
Citrus aurantium juice and peel contain the stimulant chemical synephrine as well as related stimulants such as octopamine, tyramine, N-methyltyramine, and hordeline. On this basis, Citrus aurantium has been widely marketed as a weight-loss product. However, there is no reliable evidence that Citrus aurantium is effective, and considerable reason to worry that it may cause harm (see Safety Issues). The reassuring statement made by some manufacturers that Citrus aurantium offers the “benefits of ephedra without the risks” is not supported by scientific evidence.
The only published double-blind, placebo-controlled trial on Citrus aurantium juice did not test the herb alone, but rather evaluated a combination product that also contained caffeine and St. John's wort.1 While the results were somewhat positive, overall the study was too preliminary to reach reliable conclusions. An even less reliable study evaluated the synephrine constituent of Citrus aurantium and found possible “fat burning” actions.2 In view of the weakness of the evidence in favor of Citrus aurantium, and the considerable evidence that it presents health risks, we recommend against using it for weight loss.
Other evidence, far too weak to rely upon at all, hints that synephrine-rich Citrus aurantium extracts might have antidepressant effects.3,4
Besides synephrine and other stimulants, whole Citrus aurantium peel contains including citral, limonene, and several citrus bioflavonoids, including hesperidin, neohesperidin, naringin, and rutin. Weak evidence hints that these substances might have cancer-preventive5,6 and antiviral actions.7
The essential oil of Citrus aurantium contains linalool and the fragrant substance limonene and might have antianxiety and sedative effects.8 However, neither of these proposed uses has more than extremely preliminary supporting evidence.
Many Citrus aurantium products are made from the juice and/or concentrated extracts of the peel and are said to contain a fixed percentage of synephrine or total amines. A typical recommended dosage of such products ranges from 100–150 mg two to three times daily. However, these doses may be unsafe.
Most of the safety concerns regarding citrus aurantium relate to its stimulant constituents.
The drug synephrine is known to produce many unpleasant and possibly dangerous side effects, including headache, agitation, rapid heart rate, and heart palpitations. In some people, it can cause angina pectoris, kidney damage, increased pressure in the eye, and reduced blood circulation to the heart and the extremities. The other stimulant amines in Citrus aurantium may increase such effects. There is one case report of a heart attack that appears possibly related to use of a citrus aurantium supplement,9 and another that links the herb to stroke.14Citrus aurantium juice or concentrated extracts can raise blood pressure and increase heart rate 15 and therefore should not be used by individuals with cardiovascular disease or high blood pressure. The herb should also be avoided by people with glaucoma.
Synephrine can also interact with numerous medications and other drugs, including stimulants (e.g., ephedrine, pseudoephedrine (Sudafed), Ritalin, and even caffeine) and anesthetics. The tyramine constituent of Citrus aurantium can cause deadly side effects when combined with drugs in the MAO inhibitor family.
The peel and essential oil of Citrus aurantium may cause photosensitivity (increased tendency to react to sun exposure). For this reason, combination treatment with drugs that cause the same side effect (such as sulfa antibiotics) is not recommended.
Finally, Citrus aurantium juice can alter the way that the liver processes various medications, potentially raising or lowering their levels.10-13
In particular, the drugs cyclosporine and felodipine (a calcium channel blocker) are thought to be affected by Citrus aurantium juice, but numerous other drugs may interact with it as well. For this reason, we recommend that if you are taking any medication that is critical to your health, you should not take Citrus aurantium juice.
Safety in young children, pregnant or nursing women, or people with severe liver or kidney disease has not been established.
If you are taking
Colker CM, Kalman DS, Torina GC, et al. Effects of Citrus aurantium extract, caffeine, and St. John's wort on body fat loss, lipid levels, and mood states in overweight healthy adults. Curr Ther Res. 1999;60:145–153.
Hedrei P, Gougeon R. Thermogenic effect of beta-sympathicomimetic compounds extracted from Citrus aurantium. McGill Nutrition and Food Science Center, Royal Victoria Hospital. 1997.
Kim KW, Kim HD, Jung JS, et al. Characterization of antidepressant-like effects of p-synephrine stereoisomers. Naunyn Schmiedebergs Arch Pharmacol. 2001;364:21–6.
Song DK, Suh HW, Jung JS, Wie MB, Son KH, Kim YH. Antidepressant-like effects of p-synephrine in mouse models of immobility tests. Neurosci Lett. 1996;23;214:107–10.
Miyazawa M, Okuno Y, Fukuyama M, Nakamura S, Kosaka H. Antimutagenic activity of polymethoxyflavonoids from Citrus aurantium. J Agric Food Chem. 1999;47:5239-44.
Satoh Y, Tashiro S, Satoh M, Fujimoto Y, Xu JY, Ikekawa T. Studies on the bioactive constituents of Aurantii Fructus Immaturus. Yakugaku Zasshi. 1996;116:244–50.
Kim DH, Song MJ, Bae EA, Han MJ. Inhibitory effect of herbal medicines on rotavirus infectivity. Biol Pharm Bull. 2000;23:356–8.
Carvalho-Freitas MI, Costa M. Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L. Biol Pharm Bull. 2002;25:1629–33.
Nykamp DL, Fackih MN, Compton AL. Possible association of acute lateral-wall myocardial infarction and bitter orange supplement. Ann Pharmacother. 2004;38:812–6.
Edwards DJ, Fitzsimmons ME, Schuetz EG, et al. 6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther. 1999;65:237–44.
Malhotra S, Bailey DG, Paine MF, Watkins PB. Seville orange juice–felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther. 2001;69:14–23.
Hou YC, Hsiu SL, Tsao CW, Wang YH, Chao PD. Acute intoxication of cyclosporin caused by coadministration of decoctions of the fruits of Citrus aurantium and the Pericarps of Citrus grandis. Planta Med. 2000;66:653–5.
Malhotra S, Bailey DG, Paine MF, Watkins PB. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther. 2001;69:14–23.
Bouchard NC, Howland MA, Greller HA et al. Ischemic stroke associated with use of an ephedra-free dietary supplement containing synephrine. Mayo Clin Proc. 2005;80:541-5.
Bui LT, Nguyen DT, Ambrose PJ. Blood Pressure and Heart Rate Effects Following a Single Dose of Bitter Orange. Ann Pharmacother. 2006;40:53-57.
Last reviewed September 2014 by EBSCO CAM Review Board
Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.
