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Bitter orange
•Last Updated: July 10, 2023
Bitter orange is most often used for
Last Updated:July 10, 2023
Bitter orange, or Citrus aurantium, is a citrus fruit used in Traditional Chinese Medicine for digestive issues and is also commonly found in weight loss supplements as p-synephrine, an alkaloid similar to adrenaline. Unlike ephedrine, p-synephrine has different pharmacologic properties that reduce the associated risks, and it should not be confused with the prohibited synthetic derivative m-synephrine.
Bitter orange is of interest for weight loss and athletic performance, but clinical evidence to support these benefits is lacking. Additionally, applying bitter orange oil to affected skin may help cure fungal infections, although the supporting study had limitations.
Bitter orange supplements can lead to cardiovascular issues such as increased blood pressure and heart rate, and reported adverse reactions include palpitations and fainting, particularly when combined with other stimulants like caffeine. Additionally, topical products may cause skin irritation and increased sun sensitivity, and bitter orange juice can interact with medications metabolized by the liver enzyme CYP3A4.
Bitter orange contains synephrine, which acts as a sympathetic adrenergic agonist; it stimulates the cardiovascular system and potentially increases heart rate, blood pressure, and metabolism. It may also suppress appetite by slowing food movement through the gastrointestinal tract.
Note that Bitter orange is also known as:
- Bitter Orange
- P-synephrine
- Citrus Aurantium
- Synephrine
Bitter orange should not be confused with:
A recommended dosage is 10-20mg, taken thrice a day.
Acute dosages of 50mg are also frequently used, although not thrice a day.
Research FeedRead all studies
- ^Bitter Orange: National Center for Complementary and Integrative Health(May 2020)
- ^Haaz S, Fontaine KR, Cutter G, Limdi N, Perumean-Chaney S, Allison DBCitrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update.Obes Rev.(2006-Feb)
- ^Koncz D, Tóth B, Bahar MA, Roza O, Csupor DThe Safety and Efficacy of (Bitter Orange) Extracts and -Synephrine: A Systematic Review and Meta-Analysis.Nutrients.(2022-Sep-28)
- ^Jung YP, Earnest CP, Koozehchian M, Cho M, Barringer N, Walker D, Rasmussen C, Greenwood M, Murano PS, Kreider RBEffects of ingesting a pre-workout dietary supplement with and without synephrine for 8 weeks on training adaptations in resistance-trained males.J Int Soc Sports Nutr.(2017)
- ^Ramadan W, Mourad B, Ibrahim S, Sonbol FOil of bitter orange: new topical antifungal agent.Int J Dermatol.(1996-Jun)
- ^de Jonge MLL, Kieviet LC, Sierts M, Egberink LB, van der Heyden MAGReview of Case Reports on Adverse Events Related to Pre-workout Supplements Containing Synephrine.Cardiovasc Toxicol.(2023-Jan)
- ^Nasir JM, Durning SJ, Ferguson M, Barold HS, Haigney MCExercise-induced syncope associated with QT prolongation and ephedra-free Xenadrine.Mayo Clin Proc.(2004-Aug)
- ^Bouchard NC, Howland MA, Greller HA, Hoffman RS, Nelson LSIschemic stroke associated with use of an ephedra-free dietary supplement containing synephrine.Mayo Clin Proc.(2005-Apr)
- ^Gange CA, Madias C, Felix-Getzik EM, Weintraub AR, Estes NAVariant angina associated with bitter orange in a dietary supplement.Mayo Clin Proc.(2006-Apr)
- ^Thomas JE, Munir JA, McIntyre PZ, Ferguson MASTEMI in a 24-year-old man after use of a synephrine-containing dietary supplement: a case report and review of the literature.Tex Heart Inst J.(2009)
- ^Ulbricht C, Costa D, Giese N, Isaac R, Liu A, Liu Y, Osho O, Poon L, Rusie E, Stock T, Weissner W, Windsor RCAn evidence-based systematic review of bitter orange (Citrus aurantium) by the Natural Standard Research Collaboration.J Diet Suppl.(2013-Dec)
- ^Costache II, Miron A, Hăncianu M, Aursulesei V, Costache AD, Aprotosoaie ACPharmacokinetic Interactions between Cardiovascular Medicines and Plant Products.Cardiovasc Ther.(2019)
- ^Ratamess NA, Bush JA, Kang J, Kraemer WJ, Stohs SJ, Nocera VG, Leise MD, Diamond KB, Faigenbaum ADThe effects of supplementation with P-Synephrine alone and in combination with caffeine on resistance exercise performance.J Int Soc Sports Nutr.(2015)
- ^Gutiérrez-Hellín J, Ruiz-Moreno C, Del Coso JAcute p-synephrine ingestion increases whole-body fat oxidation during 1-h of cycling at Fatmax.Eur J Nutr.(2020-Oct)
- ^Stohs SJ, Preuss HG, Keith SC, Keith PL, Miller H, Kaats GREffects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changesInt J Med Sci.(2011 Apr 28)
- ^Bui LT, Nguyen DT, Ambrose PJBlood pressure and heart rate effects following a single dose of bitter orangeAnn Pharmacother.(2006 Jan)
- ^Min B, Cios D, Kluger J, White CMAbsence of QTc-interval-prolonging or hemodynamic effects of a single dose of bitter-orange extract in healthy subjectsPharmacotherapy.(2005 Dec)
- ^Ratamess NA, Bush JA, Stohs SJ, Ellis NL, Vought IT, O'Grady EA, Kuper JD, Hasan SB, Kang J, Faigenbaum ADAcute cardiovascular effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine in human subjects: A placebo-controlled, double-blind study.Phytother Res.(2018-Jan)
- ^Haller CA, Benowitz NL, Jacob PHemodynamic effects of ephedra-free weight-loss supplements in humans.Am J Med.(2005-Sep)
- ^Tiesjema B. et alRisk assessment of synephrine. Netherlands: National Institute for Public Health and the Environment: Ministry of Health, Welfare and Sport(2017)
- ^Firenzuoli F, Gori L, Galapai CAdverse reaction to an adrenergic herbal extract (Citrus aurantium).Phytomedicine.(2005 Mar)
- ^Wason S, DiGiacinto JL, Davis MWEffects of grapefruit and Seville orange juices on the pharmacokinetic properties of colchicine in healthy subjects.Clin Ther.(2012 Oct)
- ^Di Marco MP, Edwards DJ, Wainer IW, Ducharme MPThe effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein.Life Sci.(2002 Jul 26)
- ^Malhotra S, Bailey DG, Paine MF, Watkins PBSeville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins.Clin Pharmacol Ther.(2001 Jan)
- ^Abdelkawy KS, Donia AM, Turner RB, Elbarbry FEffects of Lemon and Seville Orange Juices on the Pharmacokinetic Properties of Sildenafil in Healthy Subjects.Drugs R D.(2016 Sep)
- ^Edwards DJ, Fitzsimmons ME, Schuetz EG, Yasuda K, Ducharme MP, Warbasse LH, Woster PM, Schuetz JD, Watkins P6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein.Clin Pharmacol Ther.(1999 Mar)
- ^Stephensen TA, Sarlay R JrVentricular fibrillation associated with use of synephrine containing dietary supplement.Mil Med.(2009 Dec)
- ^Zovko Končić MGetting More Than You Paid For: Unauthorized "Natural" Substances in Herbal Food Supplements on EU Market.Planta Med.(2018 Apr)
- ^Shara M, Stohs SJ, Mukattash TLCardiovascular Safety of Oral p-Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo-Controlled Cross-over Clinical Trial.Phytother Res.(2016-May)
- ^Koh AHW, Chess-Williams R, Lohning AEHPLC-UV-QDa analysis of Citrus aurantium-labelled pre-workout supplements suggest only a minority contain the plant extract.J Pharm Biomed Anal.(2021 Jan 30)
- ^Pawar RS, Sagi S, Leontyev DAnalysis of bitter orange dietary supplements for natural and synthetic phenethylamines by LC-MS/MS.Drug Test Anal.(2020 Sep)
- ^Bitter Orange.Drugs and Lactation Database (LactMed®).(2006)
- Appetite - Stohs SJ, Preuss HG, Keith SC, Keith PL, Miller H, Kaats GREffects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changesInt J Med Sci.(2011 Apr 28)
- Blood Pressure - Penzak SR, Jann MW, Cold JA, Hon YY, Desai HD, Gurley BJSeville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults.J Clin Pharmacol.(2001-Oct)
- Blood Pressure - Shara M, Stohs SJ, Smadi MMSafety evaluation of p-synephrine following 15 days of oral administration to healthy subjects: A clinical study.Phytother Res.(2018-Jan)
- Blood Pressure - Bui LT, Nguyen DT, Ambrose PJBlood pressure and heart rate effects following a single dose of bitter orangeAnn Pharmacother.(2006 Jan)
- Blood Pressure - Min B, Cios D, Kluger J, White CMAbsence of QTc-interval-prolonging or hemodynamic effects of a single dose of bitter-orange extract in healthy subjectsPharmacotherapy.(2005 Dec)
- Blood Pressure - Ratamess NA, Bush JA, Stohs SJ, Ellis NL, Vought IT, O'Grady EA, Kuper JD, Hasan SB, Kang J, Faigenbaum ADAcute cardiovascular effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine in human subjects: A placebo-controlled, double-blind study.Phytother Res.(2018-Jan)
- Blood Pressure - Shara M, Stohs SJ, Mukattash TLCardiovascular Safety of Oral p-Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo-Controlled Cross-over Clinical Trial.Phytother Res.(2016-May)
- Blood Pressure - Koncz D, Tóth B, Bahar MA, Roza O, Csupor DThe Safety and Efficacy of (Bitter Orange) Extracts and -Synephrine: A Systematic Review and Meta-Analysis.Nutrients.(2022-Sep-28)
- Blood Pressure - Kaats GR, Miller H, Preuss HG, Stohs SJA 60day double-blind, placebo-controlled safety study involving Citrus aurantium (bitter orange) extract.Food Chem Toxicol.(2013-May)
- Hematocrit - Bush JA, Ratamess NA, Stohs SJ, Ellis NL, Vought IT, O'Grady EA, Kuper JD, Kang J, Faigenbaum ADAcute hematological and mood perception effects of bitter orange extract (p-synephrine) consumed alone and in combination with caffeine: A placebo-controlled, double-blind study.Phytother Res.(2018-Aug)
- Weight - Greenway F, de Jonge-Levitan L, Martin C, Roberts A, Grundy I, Parker CDietary herbal supplements with phenylephrine for weight loss.J Med Food.(2006)
- Carbohydrate Oxidation - Gutiérrez-Hellín J, Del Coso JEffects of p-Synephrine and Caffeine Ingestion on Substrate Oxidation during Exercise.Med Sci Sports Exerc.(2018-Sep)
- Carbohydrate Oxidation - Gutiérrez-Hellín J, Ruiz-Moreno C, Del Coso JAcute p-synephrine ingestion increases whole-body fat oxidation during 1-h of cycling at Fatmax.Eur J Nutr.(2020-Oct)
- Carbohydrate Oxidation - Gutiérrez-Hellín J, Del Coso JAcute p-synephrine ingestion increases fat oxidation rate during exerciseBr J Clin Pharmacol.(2016 Aug)
- Carbohydrate Oxidation - Gutiérrez-Hellín J, Aguilar-Navarro M, Ruiz-Moreno C, Muñoz A, Amaro-Gahete FJ, Posada-Ayala M, López-Samanes Á, Del Coso J, Varillas-Delgado DEffect of -Synephrine on Fat Oxidation Rate during Exercise of Increasing Intensity in Healthy Active Women.Nutrients.(2022-Oct-17)
- Carbohydrate Oxidation - Gutiérrez-Hellín J, Del Coso J, Aguilar-Navarro M, Varillas-Delgado D, Ruiz-Moreno C, López-Samanés Á, Amaro-Gahete FJ, Muñoz ADoes the Time of Day Play a Role in the Acute Effect of -Synephrine on Fat Oxidation Rate during Exercise in Women? A Randomized, Crossover and Double-Blind Study.Nutrients.(2022-Nov-26)
- Sprint Performance Metrics - Gutiérrez-Hellín J, Salinero JJ, Abían-Vicen J, Areces F, Lara B, Gallo C, Puente C, Del Coso JAcute consumption of p-synephrine does not enhance performance in sprint athletes.Appl Physiol Nutr Metab.(2016-Jan)
- Blood Pressure - Benjamim CJR, Júnior FWS, Porto AA, Rocha ÉMB, Santana MD, Garner DM, Valenti VE, Bueno Júnior CRBitter Orange Intake Before Submaximal Aerobic Exercise Is Safe for Cardiovascular and Autonomic Systems in Healthy Males: A Randomized Trial.Front Nutr.(2022)
- Carbohydrate Oxidation - Ratamess NA, Bush JA, Kang J, Kraemer WJ, Stohs SJ, Nocera VG, Leise MD, Diamond KB, Campbell SC, Miller HB, Faigenbaum ADThe Effects of Supplementation with p-Synephrine Alone and in Combination with Caffeine on Metabolic, Lipolytic, and Cardiovascular Responses during Resistance Exercise.J Am Coll Nutr.(2016)