Bitter orange

Last Updated: July 10, 2023

A molecule that is similar to ephedrine in mechanism, but less potent. Commonly referred to as "bitter orange", synephrine appears to be a less potent fat-burner relative to ephedrine. It may exert some minor health effects on digestion and circulation.

Bitter orange is most often used for

What is bitter orange?

Bitter orange, also known as Citrus aurantium, is a citrus fruit originally used in Traditional Chinese medicine for stomach ailments, such as constipation, diarrhea, and indigestion.[1] Today, bitter orange extract, standardized to p-synephrine content, commonly occurs in multi-ingredient formulations labeled as ephedra-free supplements for weight loss: p-synephrine is an alkaloid compound structurally similar to adrenaline and the banned dietary supplement ephedrine.[2] The pharmacologic and pharmacokinetic properties of p-synephrine vary from its structural analogues enough to mitigate the risks previously seen with ephedrine-containing supplements. [1]. p-synephrine should also not be confused with m-synephrine, a synthetic amine derivative of synephrine. m-synephrine does not meet the FDA dietary supplement definition and is a prohibited ingredient.

What are bitter orange’s main benefits?

There is interest in using bitter orange for weight loss and improvement in body composition (fat loss). However, this is not supported by clinical data.[3] Bitter orange is also used for athletic performance, but its benefit is not clear.[4]

One study found that applying bitter orange oil 20–25% to affected skin for 1 to 3 weeks was associated with cure of fungal infections like ringworm, jock itch, or athlete’s foot.[5] However, that study was limited by a lack of control group.

What are bitter orange’s main drawbacks?

Bitter orange supplements, typically standardized to synephrine content, seem to have cardiovascular stimulant effects resulting in increased blood pressure and heart rate.[3] There have been reports of adverse reactions in at least 35 people (most commonly palpitations, fainting and dizziness) after taking a synephrine-containing supplement. The specific supplement was not recorded in all cases, but for those cases where it was, the majority of the adverse events occurred with supplements in which synephrine was combined with other active ingredients, including caffeine, deterenol (a synthetic stimulant), theophylline (a bronchodilator), beta-phenylethylamine, and yohimbine. A supplement containing synephrine with caffeine was reported in most cases of cardiovascular adverse events.[6]. Examples of these events included heart rhythm issues,[7] stroke,[8] chest pain,[9] and heart attack.[10]

Topical bitter orange products may cause irritation and increased sensitivity to the sun, increasing the risk for sunburns.[11]

Bitter orange might cause drug interactions. Some studies show that bitter orange juice increases blood levels of medications broken down by the liver enzyme called cytochrome P450 (CYP) 3A4. This seems to be due to the furanocoumarin constituents contained in certain citrus fruits.[12] Theoretically, bitter orange supplements that contain furanocoumarins can affect medications that need to be processed by the CYP3A4 enzyme in the liver.

How does bitter orange work?

The synephrine in bitter oranges is thought to work as a sympathetic adrenergic agonist, stimulating receptors involved in the “fight or flight” response. These effects stimulate the cardiovascular system resulting in increased heart rate and blood pressure. Also, these effects may stimulate metabolism, resting metabolic rate and lipolysis (breakdown of fat). Appetite may also be suppressed via slowed movement of food through the gastrointestinal tract.[2] [6]

What else is Bitter orange known as?
Note that Bitter orange is also known as:
  • Bitter Orange
  • P-synephrine
  • Citrus Aurantium
  • Synephrine
Bitter orange should not be confused with:
Dosage information

A recommended dosage is 10-20mg, taken thrice a day.

Acute dosages of 50mg are also frequently used, although not thrice a day.

Examine Database: Bitter orange
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References
  1. ^Bitter Orange: National Center for Complementary and Integrative Health(May 2020)
  2. ^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)
  3. ^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)
  4. ^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)
  5. ^Ramadan W, Mourad B, Ibrahim S, Sonbol FOil of bitter orange: new topical antifungal agent.Int J Dermatol.(1996-Jun)
  6. ^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)
  7. ^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)
  8. ^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)
  9. ^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)
  10. ^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)
  11. ^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)
  12. ^Costache II, Miron A, Hăncianu M, Aursulesei V, Costache AD, Aprotosoaie ACPharmacokinetic Interactions between Cardiovascular Medicines and Plant Products.Cardiovasc Ther.(2019)
  13. ^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)
  14. ^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)
  15. ^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)
  16. ^Bui LT, Nguyen DT, Ambrose PJBlood pressure and heart rate effects following a single dose of bitter orangeAnn Pharmacother.(2006 Jan)
  17. ^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)
  18. ^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)
  19. ^Haller CA, Benowitz NL, Jacob PHemodynamic effects of ephedra-free weight-loss supplements in humans.Am J Med.(2005-Sep)
Examine Database References
  1. 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)
  2. 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)
  3. 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)
  4. Blood Pressure - Bui LT, Nguyen DT, Ambrose PJBlood pressure and heart rate effects following a single dose of bitter orangeAnn Pharmacother.(2006 Jan)
  5. 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)
  6. 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)
  7. 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)
  8. 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)
  9. 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)
  10. 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)
  11. 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)
  12. 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)
  13. 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)
  14. Carbohydrate Oxidation - Gutiérrez-Hellín J, Del Coso JAcute p-synephrine ingestion increases fat oxidation rate during exerciseBr J Clin Pharmacol.(2016 Aug)
  15. 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)
  16. 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)
  17. 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)
  18. 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)
  19. 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)