Bitter orange (Citrus aurantium)

Category

Herbs & Supplements

Synonyms

Aurantii pericarpium, auraptene, bergamot aromatherapy oil, bergamot orange, bergapten, beta-daucosterol(XI), beta-sitosterol, bigaradier, chisil, Citri aurantii fructus (CAF), Citri grandis pericarpium (CGP), Citrus amara, Citrus aurantium, Citrus aurantium dulcis, Citrus aurantium extract (CAE), Citrus aurantium L., Citrus aurantium L. var. amara, Citrus aurantium sinensis (CAS), Citrus aurantium ssp bergamia, Citrus aurantium var. amara, Citrus aurantium var. dulcis (sweet orange), Citrus bigarradia, citrus essential oils (EOs), citrus extract, Citrus L. Rutaceae, citrus peel extract, Citrus silension (CS), Citrus vulgaris, Citrus xaurantium, corteza de, Cyathifera Y. Tanaka, Daidai, Fructus aurantii, Goutou orange, Goutou sour orange, green orange, hesperidin, Kijitsu, limonene, marmalade, marmin, m-synephrine, naranja amarga, naringin, N-methyltyramine, neohesperidin, neroli oil, nobiretin, non-volatile fraction, octopamine, oil of bergamot, oxedrine, oxypeucedanin, pericarps of Citrus grandis, phenylephrine, pomeranze, Poncirus trifoliate x C. aurantiumsour orange, Rutaceae (family), Seville orange, Shangzhou Zhiqiao, sour orange, sour orange flower, sour orange leaf, sweet orange, synephrine, tangeretin, volatile oil, Xiangcheng, Xiucheng, Zhiqino, Zhi Qiao, Zhi Shi.

Background

Bitter orange (Citrus aurantium) comes from a flowering, fruit-bearing evergreen tree native to tropical Asia, but is now widely cultivated in the Mediterranean region and elsewhere. Bitter orange contains synephrine, an alkaloid with similarities to ephedrine.

Over the centuries, bitter oranges were highly valued for their food and medicinal properties. In ancient China, unripe bitter oranges were used to make zhi shi, an herbal extract used to treat constipation, improve energy (chi) and to calm nerves in cases of insomnia and shock. In the Amazon rainforest, indigenous tribes used bitter orange tea as a laxative and to relieve nausea, stomach pains, indigestion, gas and constipation.

It is claimed that bitter orange is an effective aid to weight loss and a safe alternative to ephedra. However, evidence shows some increase in heart rate and short-term calorie burn, and it may raise blood pressure and exacerbate existing heart problems. Weight loss benefits are unproven and safety questions remain. The U.S. Food and Drug Administration (FDA) banned the sale of ephedrine-containing dietary supplements. Some products previously containing ephedrine have been reformulated to include Citrus aurantium.

Evidence

DISCLAIMER: These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Aging: One low quality study indicates that a combination product including immature bitter orange may improve symptoms of aging. However, more, higher-quality studies are needed.
Grade: C

Fungal infections: Preliminary study shows promising results using oil of bitter orange as an antifungal agent. However, further evidence is needed to confirm these results.
Grade: C

Weight loss: Since the ban on ephedra, some weight loss products previously containing ephedrine have been reformulated to include bitter orange. Although bitter orange is popularly used for weight loss, the effects of bitter orange are largely unknown, and more study is needed to make a strong recommendation.
Grade: C

Dementia (behavior challenges): Bitter orange has been used in aromatherapy, although it does not appear to reduce combative, resistive behaviors in individuals with dementia. Currently, there is no evidence supporting the use of bitter orange for dementia and behavioral challenges.
Grade: D

Tradition

WARNING: DISCLAIMER: The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.
Analgesic (pain reliever), anemia, antioxidant, appetite stimulant, aromatherapy, anxiety, bed sores, blood purification, bruises, cancer, circulation, cleansing impurities from the body, constipation, cosmetic, diabetes, duodenal ulcers, dyspepsia (upset stomach), energy enhancement, epilepsy, exhaustion, eye inflammation, flatulence (gas), flavoring agent, frostbite, functional conditions, gastrointestinal disorders, headache, heart disorders, indigestion, insecticide, insomnia, kidney and bladder disorders, laxative, leukemia, muscular pain, nasal congestion, nausea, neuralgia (nerve pain), prolapsed uterus, rheumatic pain, sedative, tonic, viral infections (Rotavirus, Peste des petits ruminants).

Dosing

Adults (18 years and older)

There is no proven safe or effective dose for bitter orange as a medicinal agent. However, bitter orange has generally recognized as safe (GRAS) status for the use in foods in the United States.

Children (younger than 18 years)

There is no proven safe or effective dose for bitter orange in children.

Safety

DISCLAIMER: Many complementary techniques are practiced by healthcare professionals with formal training, in accordance with the standards of national organizations. However, this is not universally the case, and adverse effects are possible. Due to limited research, in some cases only limited safety information is available.

Allergies

Avoid in individuals with a known allergy or hypersensitivity to bitter orange or the Rutaceae family.

Side Effects and Warnings

Bitter orange has generally recognized as safe (GRAS) status for the use in foods in the United States. Despite the lack of systematic study on the safety and efficacy of bitter orange, there are several theoretical side effects that may occur from the use of bitter orange. For instance, bitter orange may cause adverse cardiovascular effects in otherwise healthy individuals; avoid in patients with preexisting cardiovascular (heart) disease. Theoretically, bitter orange may worsen narrow-angle glaucoma. It may also trigger migraine or cluster headaches. Use cautiously in patients with hyperthyroidism (overactive thyroid gland). Bitter orange may worsen the condition due to its synephrine content.

Due to its potential photosensitizing effects, use topical bitter orange preparations cautiously in patients with fair skin.

Avoid using in patients with intestinal colic based on reports of convulsion and death in children who consume large amounts of bitter orange peel. Also avoid using in patients taking QT-interval prolonging drugs or with long QT interval syndrome. Theoretically, bitter orange might increase the risk of ventricular arrhythmias (irregular heart rhythms).

Avoid using with drugs or dietary supplements with stimulant properties. Concurrent use might increase the risk of hypertension (high blood pressure) and adverse cardiovascular effects.

Pregnancy and Breastfeeding

Bitter orange is not recommended in pregnant or breastfeeding women due to a lack of available scientific evidence.

Interactions

Interactions with Drugs

Theoretically, bitter orange might be antagonized by alpha blocking agents. Caution is advised.

Theoretically, concomitant use of bitter orange and beta blockers might cause acute hypertension (high blood pressure).

Large amounts of caffeine might increase the risk of hypertension and adverse cardiovascular effects with bitter orange due to synephrine content.

Theoretically, concurrent use of monoamine oxidase inhibitors (MAOIs) with synephrine-containing bitter orange preparations might increase the blood pressure raising effects of synephrine and potentially cause hypertensive crisis. Bitter orange contains tyramine, octopamine, and synephrine, which are MAO substrates. Caution is advised when taking bitter orange with other MAOIs.

Bitter orange juice may interfere with the way the body processes certain drugs using the liver's "cytochrome P450" enzyme system. As a result, the levels of these drugs may be decreased in the blood, and reduce the intended effects. Patients taking any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.

Oil of bergamot, which comes from Citrus aurantium ssp. Bergamia, may cause hyperpigmentation, dermatitis or make a patient more sensitive to laser treatment. Caution is advised when taking bitter orange with other photosensitizing agents.

Bitter orange might prolong the QT interval in some patients, especially when in combination with other stimulants such as caffeine. Theoretically, bitter orange could have an additive effect when combined with drugs that prolong the QT interval and potentially increase the risk of ventricular arrhythmias (irregular heart beats). Use of bitter orange with other cardioactive agents may also increase this risk.

Theoretically, drugs with central nervous system (CNS) stimulant properties, such as phenylpropanolamine and pseudoephedrine, might increase the risk of hypertension and adverse cardiovascular effects of bitter orange due to synephrine content.

Theoretically, bitter orange may interact with thyroid medications, or worsen hyperthyroidism due to its synephrine content.

Interactions with Herbs and Dietary Supplements

Theoretically, anti-adrenergic herbs or supplements might antagonize bitter orange. Caution is advised.

Honey reduces the absorption of naringin, a flavone glycoside of bitter orange.

Theoretically, concurrent use of herbs with monoamine oxidase inhibitor activity with synephrine-containing bitter orange preparations might increase the blood pressure raising effects of synephrine and potentially cause hypertensive crisis. Bitter orange contains tyramine, octopamine, and synephrine, which are MAO substrates. Caution is advised when taking bitter orange with other herbs with MAOI effects.

Bitter orange may interfere with the way the body processes certain herbs or supplements using the liver's "cytochrome P450" enzyme system. As a result, the levels of other herbs or supplements may become too high in the blood. It may also alter the effects that other herbs or supplements possibly have on the P450 system.

Theoretically, Panax ginseng might prolong the QT interval on electrocardiogram (ECG). Thus, combining Panax ginseng and bitter orange might have an additive effect on the QT interval and increase the risk for arrhythmias (irregular heart beats). Use of bitter orange with other cardioactive herbs or supplements may also increase this risk.

Oil of bergamot, which comes from Citrus aurantium ssp. Bergamia, may cause hyperpigmentation, dermatitis or make a patient more sensitive to laser treatment. Caution is advised when taking bitter orange with other photosensitizing herbs.

Theoretically, herbs and supplements with stimulant properties, such as ephedra, guarana, and mate, might increase the risk of hypertension (high blood pressure) and adverse cardiovascular effects with bitter orange due to synephrine content.

Theoretically, bitter orange may interact with herbs affecting the thyroid, or worsen hyperthyroidism due to its synephrine content.

Attribution

This information is based on a systematic review of scientific literature, and was peer-reviewed and edited by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com): Linda Poon, PharmD (Northeastern University); Erica Seamon, PharmD (Nova Southeastern University); Shaina Tanguay-Colucci, BS (Natural Standard Research Collaboration); Catherine Ulbricht, PharmD (Massachusetts General Hospital); Wendy Weissner, BA (Natural Standard Research Collaboration).

Bibliography

DISCLAIMER: Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

Bent S, Padula A, Neuhaus J. Safety and efficacy of citrus aurantium for weight loss. Am J Cardiol 11-15-2004;94(10):1359-1361.

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(4):541-545.

Bui LT, Nguyen DT, Ambrose PJ. Blood pressure and heart rate effects following a single dose of bitter orange. Ann Pharmacother 2006;40(1):53-57.

Fang F, Dong M, Zhu H. [Effect of Citrus aurantium extract on L-type calcium currents in ventricular myocytes of single guinea pigs]. Hunan Yi Ke Da Xue.Xue Bao. 2003;28(4):353-356.

Firenzuoli F, Gori L, Galapai C. Adverse reaction to an adrenergic herbal extract (Citrus aurantium). Phytomedicine 2005;12(3):247-248.

Fugh-Berman A, Myers A. Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research. Exp Biol Med (Maywood.) 2004;229(8):698-704.

Gougeon R, Harrigan K, Tremblay JF, et al. Increase in the thermic effect of food in women by adrenergic amines extracted from citrus aurantium. Obes Res 2005;13(7):1187-1194.

Gray S, Woolf AD. Citrus aurantium used for weight loss by an adolescent with anorexia nervosa. J Adolesc.Health 2005;37(5):414-415.

Haller CA, Benowitz NL, Jacob P III. Hemodynamic effects of ephedra-free weight-loss supplements in humans. Am J Med 2005;118(9):998-1003.

Hosseinimehr SJ, Karami M. Citrus extract modulates genotoxicity induced by cyclophosphamide in mice bone marrow cells. J Pharm Pharmacol 2005;57(4):505-509.

Hosseinimehr SJ, Tavakoli H, Pourheidari G, et al. Radioprotective effects of citrus extract against gamma-irradiation in mouse bone marrow cells. J Radiat Res (Tokyo) 2003;44(3):237-241.

Martin KW, Ernst E. Herbal medicines for treatment of fungal infections: a systematic review of controlled clinical trials. Mycoses 2004;47(3-4):87-92.

McBride BF, Karapanos AK, Krudysz A, et al. Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial. JAMA 1-14-2004;291(2):216-221.

Nasir JM, Durning SJ, Ferguson M, et al. Exercise-induced syncope associated with QT prolongation and ephedra-free Xenadrine. Mayo Clin Proc 2004;79(8):1059-1062.

Nykamp DL, Fackih MN, Compton AL. Possible association of acute lateral-wall myocardial infarction and bitter orange supplement. Ann Pharmacother 2004;38(5):812-816.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.