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Bitter orange (Citrus aurantium)

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Related terms
Background
Evidencetable
Tradition
Dosing
Safety
Interactions
Attribution
Bibliography

Related Terms
  • Aurantii pericarpium, auraptene, bergamot aromatherapy oil, bergamot orange, bergapten, beta-daucosterol(XI), beta-sitosterol, bigaradier, bitter orange extract, bitter orange peel, chisil, Citri aurantii fructus (CAF), Citri grandis pericarpium (CGP), Citrus amara, Citrus aurantium, Citrus aurantiumdulcis, Citrus aurantium extract (CAE), Citrus aurantium L., Citrus aurantium L. var. amara, Citrus aurantiumsinensis (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 unshiu Marcovitch, Citrus vulgaris, Citrus xaurantium, corteza de naranja (Spanish), Cyathofora Y.Tanaka, Daidai, flavanones, furocoumarins, fructus Aurantii, Goutou orange, Goutou sour orange, green orange, hesperidin, hordenine, Kijitsu, limonene, marmalade, marmin, meta-synephrine, m-synephrine, naranja amarga (Spanish), naringin, neohesperidin, neroli oil, N-methyltyramine, nobiretin, nonvolatile fraction, octopamine, oil of bergamot, oxedrine, oxypeucedanin, oxy-psoralen (5-[(6',7'-dihydroxy-3',7'-dimethyl-2-octenyl)], para-octopamine, para-synephrine, pericarps of Citrus grandis, phenethylamine alkaloids, phenylephrine, pomeranze, Poncirus trifoliata x C. aurantium sour orange, p-synephrine, Rutaceae (family), satsuma mandarins, Seville, Seville orange, shangzhou zhiqiao, sour orange, sour orange flower, sour orange juice, sour orange leaf, sweet orange, synephrine, synephrine alkaloids, synephrine HCl, synthetic synephrine, tangeretin, tyramine, volatile oil, xiangcheng, xiucheng, zhiqino, zhi qiao, zhi shi.
  • Combination product examples: Advantra Z® (Nutratech, Inc.); dannang recipe no. 2 (aucklandia root, red peony root, giant knotweed rhizome, scutellaria root, honeysuckle flower, forsythia fruit, rhubarb, immature bitter orange, magnolia bark, peach kernel, red sage root, licorice root, boiled with water); Lean System 7T; Metabolift Ephedra-Free Formula® (Twinlab Corporation); NutrexT Lipo-6x; Rauvolfia-Citrus tea (foliage of Rauwolfia vomitoria and bitter orange fruit); Stacker 2 Ephedra-Free (NVE Pharmaceuticals); Xenadrine EFX® (Cytodyne Technologies); Zhizhu® (rhizoma Atractylodis macrocephalae and fructus Aurantii immaturus; either Citrus aurantium L. (IFCA) or Citrus sinensis Osbeck (IFCS))

Background
  • Bitter orange (Citrus aurantium) comes from a flowering evergreen tree of tropical Asia. Bitter orange trees are now widely grown in the Mediterranean region and elsewhere.
  • Bitter orange contains synephrine, a compound similar to ephedrine. 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 bitter orange
  • Bitter orange is commonly used in dietary supplements for fat loss and as an appetite suppressant. It is claimed that bitter orange is an effective aid to weight loss and a safe alternative to ephedra. Various adverse effects have been contributed to bitter orange or p-synephrine. However, there is little concrete evidence to suggest the lack of safety of these products.

Evidence Table

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. GRADE *


Use of bitter orange before surgery improved anxiety. A combination product with bitter orange improved symptoms associated with gallbladder removal. However, the effect of bitter orange alone is unclear. Further research is needed.

C


Limited research indicates that a combination product with bitter orange may improve symptoms of aging. However, more, high-quality studies are needed.

C


Bitter orange has been used in aromatherapy. Bitter orange does not seem to reduce combative, resistive behaviors in people with dementia. Further studies are needed on this topic.

C


Limited research reports that bitter orange may reduce blood sugar after meals and during fasting. Further studies on the effect of bitter orange alone are needed.

C


A combination of synephrine (a component of bitter orange) and caffeine may make exercise feel easier and increase blood pressure and blood sugar. Further research on bitter orange is needed.

C


Preliminary research shows promising results using bitter orange oil as an antifungal agent. However, further evidence is needed to confirm these results.

C


Early research suggests that bitter orange pills may benefit people with indigestion. Further research is needed before a conclusion may be made.

C


A component of bitter orange, p-synephrine, lacked effect on mood and energy. Further research is needed before a conclusion may be made.

C


Research suggests that weight loss may be enhanced by a bitter orange product. Additional high-quality studies on bitter orange alone are needed.

C
* Key to grades

A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence for this use (it may not work)
F: Strong scientific evidence against this use (it likley does not work)


Tradition / Theory

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.

  • Anemia, antimicrobial, antioxidant, anxiety, appetite stimulant, aromatherapy, bedsores, blood purification, bruises, cancer, circulation, constipation, cosmetic, energy enhancement, epilepsy, eye inflammation, flavoring agent, frostbite, functional conditions, gas, gastrointestinal disorders, headache, heart disease, heart disorders, inflammation, insecticide, insomnia, kidney and bladder disorders, liver protection, nasal congestion, nausea, neuralgia (pain from nerve damage), pain, prolapsed uterus, sedative, tonic, viral infections (Rotavirus, peste des petits ruminants).

Dosing

Adults (18 years and older)

  • General: Up to 80 milligrams of p-synephrine (component of bitter orange) has been taken daily by mouth alone or in combination with other ingredients, including caffeine.
  • For an adjunct to surgery, one milliliter of bitter orange blossom per kilogram has been taken by mouth two hours before surgery.
  • For fungal infections, a 25% mixture of bitter orange oil three times daily, 20% bitter orange oil in alcohol three times daily, and 100% bitter orange oil once daily have been applied to the skin.
  • For indigestion, six grams of Zhizhu® pills containing bitter orange and other herbs has been taken by mouth three times daily after meals for four weeks.
  • For mood enhancement, V-8® juice containing 50 milligrams of p-synephrine from bitter orange extract (Advantra Z®) has been taken by mouth.
  • For weight loss, up to 80 milligrams of p-synephrine has been taken by mouth daily.

Children (younger than 18 years)

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

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid with known allergy or sensitivity to bitter orange, its constituents, or members of the Rutaceae family.

Side Effects and Warnings

  • Bitter orange is likely safe when taken by mouth in amounts normally found in food.
  • Bitter orange is possibly safe when the essential oil is used by inhalation as aromatherapy. Bitter orange is likely safe when taken by mouth at levels of up to 50 milligrams of p-synephrine or p-octopamine alone, or up to 40 milligrams p-synephrine or p-octopamine in combination with up to 320 milligrams of caffeine daily.
  • Bitter orange is likely safe when taken by mouth daily in single doses of up to 70 milligrams of p-synephrine alone or divided doses of up to 100 milligrams of p-synephrine alone. Bitter orange is likely safe when taken by mouth in single doses of 40 milligrams of p-synephrine in combination with 320 milligrams of caffeine or divided doses of 70 milligrams of p-synephrine in combination with 400 milligrams of caffeine.
  • Bitter orange may cause low blood pressure. Caution is advised in people taking drugs or herbs and supplements that lower blood pressure.
  • Bitter orange contains substances that interact with MAOIs. Tyramine- or tryptophan-containing foods may cause dangerously high blood pressure when taken at the same time as agents that have properties similar to monoamine oxidase inhibitor drugs (MAOIs). These include protein foods that have been aged or preserved. Specific examples of foods are anchovies, avocados, bananas, bean curd, beer (alcohol-free or reduced-alcohol), bologna, caffeine (large amounts), caviar, champagne, cheeses (particularly aged, processed, or strong varieties), chocolate, dry sausage, fava beans, figs, herring (pickled), liver (particularly chicken), meat tenderizers, papaya, protein extracts or powder, raisins, salami, shrimp paste, sour cream, soy sauce, wine (particularly chianti), yeast extracts, and yogurt.
  • Bitter orange may lower blood sugar levels. Caution is advised in people with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.
  • Use cautiously in people with gastrointestinal disorders, headache, heart disease, musculoskeletal disorders, narrow-angle glaucoma, respiratory disorders, or thyroid conditions. Use cautiously when bitter orange is taken alone or applied to the skin.
  • Use cautiously in people taking agents metabolized by cytochrome P450, alpha-blocking agents, antiadrenergic agents, beta-blockers, CNS stimulants or other supplement stimulants (including caffeine), decongestant-containing cold preparations, or thyroid medications.
  • Avoid with known allergy or sensitivity to bitter orange, its constituents, or members of the Rutaceae family. Avoid bitter orange essential oil taken by mouth or applied to the skin. Avoid bitter orange in children or pregnant or breastfeeding women.
  • Bitter orange may also cause abnormally high or low heart rate, antidepressant effects, blood clots, cardiovascular toxicity, chest pain, colon inflammation, difficulty in concentrating, dizziness, exercise-induced fainting, fainting, heart attack, heart rhythm disorder, heart-related adverse effects, increased sensitivity to the sun, memory loss, migraine or cluster headache, narrowing of blood vessels, relaxation of lung muscle, rhabdomyolysis (severe exercise-induced muscle breakdown), seizures, skin irritation, stroke, unsteady gait, and weight loss.
  • Note: Although various adverse and toxic effects have been attributed to bitter orange and/or p-synephrine, there is little concrete evidence to suggest the lack of safety of these products.

Pregnancy and Breastfeeding

  • There is a lack of sufficient data on the use of bitter orange during pregnancy or lactation. However, bitter orange is likely safe when taken in amounts commonly found as food.
  • It is suggested to avoid high doses of bitter orange, especially during lactation, due to its finding in combination with caffeine in weight loss products and the potential for decreased milk production.

Interactions

Interactions with Drugs

  • Bitter orange may lower blood sugar levels. Caution is advised when using medications that may also lower blood sugar. People taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
  • Bitter orange 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 increased in the blood and may cause increased effects or potentially serious adverse reactions. People using any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.
  • Bitter orange may cause low blood pressure. Caution is advised in people taking drugs that lower blood pressure.
  • Bitter orange contains substances that interact with MAOIs. Tyramine/tryptophan containing foods may cause dangerously high blood pressure when taken at the same time as agents that have properties similar to monoamine oxidase inhibitor drugs (MAOIs). These include protein foods that have been aged or preserved. Specific examples of foods are anchovies, avocados, bananas, bean curd, beer (alcohol-free or reduced-alcohol), bologna, caffeine (large amounts), caviar, champagne, cheeses (particularly aged, processed, or strong varieties), chocolate, dry sausage, fava beans, figs, herring (pickled), liver (particularly chicken), meat tenderizers, papaya, protein extracts or powder, raisins, salami, shrimp paste, sour cream, soy sauce, wine (particularly chianti), yeast extracts, and yogurt.
  • Bitter orange may also interact with agents for anxiety; agents for cancer and obesity; agents for depression, such as monoamine oxidase inhibitors (MAOIs); agents for the brain, eyes, heart, lung, skin, stomach, or intestines; agents that increase sensitivity to light; agents that narrow blood vessels; alpha-blockers; antiadrenergics; antibiotics; antifungal agents; antihelminthics; anti-inflammatory agents; antiparasitics; antiviral agents; beta-blockers; caffeine; CNS stimulants; decongestants; insecticides; musculoskeletal agents; psoralens; QT-prolonging drugs; and thyroid hormones.

Interactions with Herbs and Dietary Supplements

  • Bitter orange may lower blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.
  • 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.
  • Bitter orange may cause low blood pressure. Caution is advised in people taking herbs or supplements that lower blood pressure.
  • Bitter orange contains substances that interact with MAOIs. Tyramine- or tryptophan-containing foods may cause dangerously high blood pressure when taken at the same time as agents that have properties similar to monoamine oxidase inhibitor drugs (MAOIs). These include protein foods that have been aged or preserved. Specific examples of foods are anchovies, avocados, bananas, bean curd, beer (alcohol-free or reduced-alcohol), bologna, caffeine (large amounts), caviar, champagne, cheeses (particularly aged, processed, or strong varieties), chocolate, dry sausage, fava beans, figs, herring (pickled), liver (particularly chicken), meat tenderizers, papaya, protein extracts or powder, raisins, salami, shrimp paste, sour cream, soy sauce, wine (particularly chianti), yeast extracts, and yogurt.
  • Bitter orange may also interact with antiadrenergic herbs and supplements; antibacterials; antidepressant herbs and supplements, such as monoamine oxidase inhibitors (MAOIs); antifungals; antihelminthics; anti-inflammatory herbs and supplements; antioxidants; antiparasitics; antivirals; caffeine; decongestants; flavonoids; herbs and supplements eliminated by the kidney; herbs and supplements for anxiety; herbs and supplements for cancer or obesity; herbs and supplements for the brain, eyes, heart, lungs, stomach, or intestines; herbs and supplements that increase sensitivity to light; herbs and supplements that narrow blood vessels; herbs and supplements that protect against radiation; honey; insecticides; musculoskeletal herbs and supplements; Panax ginseng; psoralens; and stimulants.

Attribution
  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Akhlaghi, M., Shabanian, G., Rafieian-Kopaei, M., Parvin, N., Saadat, M., and Akhlaghi, M. Citrus aurantium blossom and preoperative anxiety. Rev Bras.Anestesiol. 2011;61(6):702-712.
  2. Campbell-Tofte, J. I., Molgaard, P., Josefsen, K., Abdallah, Z., Hansen, S. H., Cornett, C., Mu, H., Richter, E. A., Petersen, H. W., Norregaard, J. C., and Winther, K. Randomized and double-blinded pilot clinical study of the safety and anti-diabetic efficacy of the Rauvolfia-Citrus tea, as used in Nigerian traditional medicine. J Ethnopharmacol. 1-27-2011;133(2):402-411.
  3. Higgins, J. P., Tuttle, T. D., and Higgins, C. L. Energy beverages: content and safety. Mayo Clin Proc. 2010;85(11):1033-1041.
  4. Jalili, J., Askeroglu, U., Alleyne, B., and Guyuron, B. Herbal products that may contribute to hypertension. Plast.Reconstr.Surg. 2013;131(1):168-173.
  5. Kaats, G. R., Miller, H., Preuss, H. G., and Stohs, S. J. A 60day double-blind, placebo-controlled safety study involving Citrus aurantium (bitter orange) extract. Food Chem Toxicol. 2013;55:358-362.
  6. Lynch B. Review of the safety of p-synephrine and caffeine. Intertek-Cantox Report, 2013;1-20.
  7. Rasmussen, C. B., Glisson, J. K., and Minor, D. S. Dietary supplements and hypertension: potential benefits and precautions. J Clin Hypertens.(Greenwich.) 2012;14(7):467-471.
  8. Seifert, J. G., Nelson, A., Devonish, J., Burke, E. R., and Stohs, S. J. Effect of acute administration of an herbal preparation on blood pressure and heart rate in humans. Int J Med Sci 2011;8(3):192-197.
  9. Shara M, Stohs SJ. Safety evaluation of Bitter orange extract () in healthy volunteers. J.Amer.Coll.Nutr. 2011;30:358.
  10. Stohs SJ, Preuss HG. The safety of Bitter orange (Citrus aurantium) and its primary protoalkaloid p-synephrine. HerbalGram 2011;89:34-39.
  11. Stohs SJ. Assessment of the adverse event reports associated with Citrus aurantium (Bitter orange) from April 2004 to October 2009. J.Funct.Foods 2011;2:235-238.
  12. Stohs, S. J., Preuss, H. G., and Shara, M. A review of the human clinical studies involving Citrus aurantium (bitter orange) extract and its primary protoalkaloid p-synephrine. Int J Med Sci 2012;9(7):527-538.
  13. Stohs, S. J., Preuss, H. G., Keith, S. C., Keith, P. L., Miller, H., and Kaats, G. R. Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes. Int J Med Sci 2011;8(4):295-301.
  14. Wason, S., DiGiacinto, J. L., and Davis, M. W. Effects of grapefruit and Seville orange juices on the pharmacokinetic properties of colchicine in healthy subjects. Clin Ther 2012;34(10):2161-2173.
  15. Wu, H., Jing, Z., Tang, X., Wang, X., Zhang, S., Yu, Y., Wang, Z., Cao, H., Huang, L., Yu, Y., and Wang, Y. To compare the efficacy of two kinds of Zhizhu pills in the treatment of functional dyspepsia of spleen-deficiency and qi-stagnation syndrome: a randomized group sequential comparative trial. BMC.Gastroenterol 2011;11:81.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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