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Bergamot Oil

Scientific Name(s): Citrus bergamia Risso et Poiteau
Common Name(s): Bergamot, Oleum bergamotte

Clinical Overview

Use

Bergamot oil is widely used as a flavoring and scenting agent. Research has been conducted to evaluate bergamot oil's potential cardiovascular, antifungal, and CNS (eg, antinociceptive, anti-anxiety, antidepressant) effects. However, there are limited quality clinical trials to support any of these uses.

Dosing

Clinical studies are lacking to provide dosage recommendations. Bergamot oil is principally used in aromatherapy. Direct topical use is discouraged due to psoralen photodermatotoxicity; internal use may cause muscular cramping and should also be avoided.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Bergapten, a furocoumarin found in bergamot oil, has been shown to alter potassium channel currents, causing twitching and muscle cramps. There is a case report of a 44-year-old man who experienced muscle cramps, fasciculations, paresthesias, and blurred vision after consuming up to 4 L (approximately 1 gallon) of Earl Grey tea flavored with bergamot oil daily. All symptoms disappeared after switching to pure black tea.

Toxicology

Photosensitizing components can induce rashes and pathologic cellular changes. Contact with leave-on skin products containing bergamot oil should be limited to 0.4%, with no restrictions on rinse-off products or non–skin contact products.

Source

The bergamot, a small tree native to tropical Asia, is cultivated extensively in Reggio Calabria, a coastal city in southern Italy, and cultivated on a smaller scale on the Ivory Coast and in Argentina and Brazil. The trees have star-shaped white flowers; round, yellow fruits; and large, dark-green, oval-shaped leaves similar to those of lemon trees.Navarra 2015 The peel of the fresh, nearly ripe fruit is the source of bergamot oil, which is composed of volatile (93% to 96%) and nonvolatile (4% to 7%) fractions.Navarra 2015 Bergamot is related to bitter orange (Citrus aurantium); a synonym of C. bergamia is Citrus aurantium L. subspecies bergamia.Khan 2009, USDA 2018 C. bergamia should not be confused with scarlet bergamot (Monarda didyma L.) or wild bergamot (Monarda fistulosa L.), which belong to the mint family.

History

Bergamot oil is used as a citrus flavor and is often added to perfumes and cosmetics. Bergamot oil is used to flavor Earl Grey tea Verzera 2003 and halva, a Middle Eastern sesame paste confection. In Italian folk medicine, bergamot oil has been used to treat fever; parasitic disease; mouth, skin, respiratory and urinary tract, and gonococcal infections; leucorrhoea; vaginal pruritus; tonsillitis; and sore throat.Navarra 2015

Chemistry

The oil is obtained by cold press.Cappello 2016 Further purification by vacuum distillation, solvent extraction, or chromatography yields terpeneless (rectified) bergamot oil.Khan 2009 Bergamot oil is a complex mixture of more than 300 compounds. The most prevalent compounds are linalyl acetate (31%), linalool (11%), and limonene (36%).Han 2017 The quality of bergamot oil is determined according to the amounts of oxygenated compounds (ie, linalool, linalyl acetate). Furocoumarins include bergapten (approximately 0.4% 5-methoxypsoralen [5-MOP]),Finsterer 2002 bergamottin (5-geranyloxypsoralen),Finsterer 2002, Morliere 1991 citropten (5,7-dimethoxycoumarin),Finsterer 2002, Makki 1991 and others. Rectified bergamot oil contains lower concentrations of terpenes and has no coumarins.Belsito 2007, Khan 2009, Melliou 2009 Only 2 flavonoids, sinensetin and tetra-O-methylscutellarein, have been detected in the oil component of bergamot.Cappello 2016

Uses and Pharmacology

Antifungal effects

Animal and in vitro data

Bergamot oil concentrations of 0.5% to 1% inhibited growth of the mycotoxigenic Fusarium species Fusarium sporotrichioides, Fusarium graminearum, and Fusarium langsethiae, all known contaminants of cereals.Morcia 2017 At a minimum inhibitory concentration (MIC) of 0.3% (v/v), bergamot oil showed antifungal effects against planktonic Candida albicans cells in mouse fibroblasts.Serra 2018

Antineoplastic effects

In vitro data

Antiproliferative effects of bergamot oil have been studied in vitro using human cancer cell lines.Berliocchi 2011, Celia 2013, Cosentino 2014, Navarra 2015

Cardiovascular effects

Animal data

Smooth muscle relaxation induced by bergamot oil has been demonstrated in mouse aorta, possibly via activation of potassium ion channels and/or inhibition of calcium ion influx.Kang 2013

Clinical data

In a randomized, controlled clinical trial, patients awaiting ambulatory surgery and exposed to bergamot oil aromatherapy for 30 minutes showed a decrease in blood pressure and heart rate.Ni 2013

CNS effects

Animal data

Antinociceptive effects of bergamot oil have been reported in studies in rodents.Bagetta 2010, Katsuyama 2015, Sakurada 2011 In animal studies, anxiolytic and sedative properties of bergamot oil given systemically and by inhalation have been reported.Bagetta 2010, Saiyudthong 2011 A calcium ion–dependent increase in extracellular aspartate, glycine, and taurine in the CNS has been reported as a potential mechanism of action.Bagetta 2010 One study in rats reported a reduced corticosterone response to acute stress with inhaled bergamot oil.Saiyudthong 2011 Further studies suggest activity at the opioid receptors; the opioid receptor antagonist naloxone prevented antinociceptive effects of bergamot oil.Rombola 2016 Another study showed that bergamot oil induces anxiolytic-like and relaxant effects in the behavioral tasks of rats.Rombola 2017

Clinical data

Healthy adults administered a 10% solution of blended essential oil (containing lavender and bergamot and topically massaged into the skin) reported feeling more calm and relaxed. These findings indicate a decrease in autonomic arousal and deactivation at the behavioral level; thus, these effects may be characterized by the "concept of relaxing effect." One possible mechanism is that the oil stimulates the brain to release serotonin. Furthermore, the oil may interact with central structures that control the level of autonomic and/or behavioral arousal. The synergistic effects of the lavender and bergamot oil blend suggested benefit in treating depression and anxiety.Hongratanaworakit 2011

In a randomized, controlled clinical trial, patients awaiting ambulatory surgery and exposed to bergamot oil aromatherapy for 30 minutes showed a decrease in State Trait Anxiety Inventory (STAI) scores.Ni 2013 Exposure to 100% bergamot oil diluted to 2% showed that aromatherapy sessions lasting at least 15 minutes alleviated symptoms of physical and psychological stress by causing a relaxing effect.Liu 2013 In an experiment in healthy volunteers, salicary cortisol levels were lowered with bergamot oil aromatherapy.Watanabe 2015 An 8-week clinical study exploring the effects of bergamot oil inhalation on mental well-being of patients at a mental health treatment center showed positive results compared with the control group. Overall, the treatment group reported higher affect scores, smaller increases in negative affect, and higher scores of feeling proud and active; however, patients in the treatment group also reported feeling nervous. Bergamot oil aromatherapy may provide beneficial effects on mood and mental well being, as measured by the Positive and Negative Affect Schedule (PANAS).Han 2017

Dosing

Clinical studies are lacking to provide dosage recommendations. Bergamot oil is principally used in aromatherapy. Direct topical use is discouraged due to psoralen photodermatotoxicity; internal use may cause muscular cramping and should also be avoided.

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Direct topical use is discouraged due to psoralen photodermatotoxicity; internal use may cause muscular cramping and should also be avoided.Kaddu 2001 Bergapten, a furocoumarin found in bergamot oil, has been shown to alter potassium channel currents, causing twitching and muscle cramps. There is a case report of a 44-year-old man who experienced muscle cramps, fasciculations, paresthesias, and blurred vision after consuming up to 4 L (approximately 1 gallon) of Earl Grey tea (flavored with bergamot oil) daily. All symptoms disappeared after switching to pure black tea.Finsterer 2002 When used in aromatherapy, bergamot oil is well tolerated.Han 2017

Toxicology

Some furocoumarins (eg, bergapten and xanthotoxin, known as 5-MOP and 8-MOP, respectively) have been shown to be phototoxic in humans.Kejlova 2007, Khan 2009, Zaynoun 1977 The nonvolatile compound bergapten is responsible for the phototoxic effects; however, production of bergapten-free oil is possible.Sicari 2018 A peak photosensitivity effect is reached 2 to 72 hours after topical administration of bergamot oil followed by irradiation.Dubertret 1990, Zaynoun 1977 Hyperpigmentation of the face and other areas exposed to the sun is thought to be due to the photosensitizing effects of cosmetics that contain these compounds. Phototoxic reactions can be affected by a variety of factors, including vehicle, concentration, hydration of skin, skin site, interval between local application of bergamot oil and irradiation, degree of skin pigmentation, and ability to tan.Zaynoun 1977 Inform patients of a potential phototoxic reaction caused by exposure to aerosolized bergamot aromatherapy oil with subsequent UVA exposure.Kaddu 2001 The furocoumarins can induce genetic changes in cells exposed to UV light even in concentrations as low as 5 ppm.Young 1990 These changes can be minimized by the application of a cinnamate-containing sunscreen,Averbeck 1990 but sunscreens in low concentrations (up to 1%) added to perfumes cannot suppress the phototoxicity of bergamot oil on human skin.Wang 2002 In the 48th Amendment of Standards, the International Fragrance Association (IFRA) expressed restrictions for bergamot oil due to phototoxic effects. IFRA recommends that contact with leave-on skin products containing bergamot oil be limited to 0.4% when the application area is exposed to the sun, with no restriction on rinse-off products or non–skin contact products.IFRA 2015 When tested in vitro on mouse fibroblast cells, bergamot oil induced a probable phototoxic effect at photoirritation factor (PIF) values of 2.7 and 4.6 and mean photo effect (MPE) values of 0.139 and 0.276. When both values are taken into consideration together, a substance is considered "probably phototoxic" if PIF value falls between 2.1 and 4.9 and MPE value falls between 0.1 and 0.15.Binder 2016 Bergamot oil also decreased cell viability after UV light exposure by approximately 50% in concentration. Decreased rod outer segments production and mitochondrial dysfunction are possible contributing factors to essential oil toxicity.

References

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Bagetta G, Morrone LA, Rombolà L, et al. Neuropharmacology of the essential oil of bergamot. Fitoterapia. 2010;81(6):453-461.20093169
Belsito EL, Carbone C, Di Gioia ML, et al. Comparison of the volatile constituents in cold-pressed bergamot oil and a volatile oil isolated by vacuum distillation. J Agric Food Chem. 2007;55(19):7847-7851.17696485
Bergamot oil expressed. International Fragrance Association website. http://www.ifraorg.org/en-us/search/s/bergamot#.W42Z9l4o59C. Published 2015. Accessed September 3, 2018.
Berliocchi L, Ciociaro A, Russo R, et al. Toxic profile of bergamot essential oil on survival and proliferation of SH-SY5Y neuroblastoma cells. Food Chem Toxicol. 2011;49(11):2780-2792.21878361
Binder S, Hanáková A, Tománková K, et al. Adverse phototoxic effect of essential plant oils on NIH 3T3 cell line after UV light exposure. Cent Eur J Public Health. 2016;24(3):234-240.27755863
Cappello AR, Dolce V, Iacopetta D, et al. Bergamot (Citrus bergamia Risso) flavonoids and their potential benefits in human hyperlipidemia and atherosclerosis: an overview. Mini Rev Med Chem. 2016;16(8):619-629.26156545
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Citrus aurantium. USDA, NRCS. 2018. The PLANTS Database (http://plants.usda.gov, 3 September 2018). National Plant Data Team, Greensboro, NC 27401-4901 USA.
Cosentino M, Luini A, Bombelli R, Corasaniti MT, Bagetta G, Marino F. The essential oil of bergamot stimulates reactive oxygen species production in human polymorphonuclear leukocytes. Phytother Res. 2014;28(8):1232-1239.24458921
Dubertret L, Serraf-Tircazes D, Jeanmougin M, Morlière P, Averbeck D, Young AR. Phototoxic properties of perfumes containing bergamot oil on human skin: photoprotective effect of UVA and UVB sunscreens. J Photochem Photobiol B. 1990;7(2-4):251-259.2128327
Finsterer J. Earl Grey tea intoxication. Lancet. 2002;359(9316):1484.11988248
Han X, Gibson J, Eggett DL, Parker TL. Bergamot (Citrus bergamia) essential oil inhalation improves positive feelings in the waiting room of a mental health treatment center: a pilot study. Phytother Res. 2017;31(5):812-816.28337799
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Kaddu S, Kerl H, Wolf P. Accidental bullous phototoxic reactions to bergamot aromatherapy oil. J Am Acad Dermatol. 2001;45(3):458-461.11511848
Kang P, Suh SH, Min SS, Seol GH. The essential oil of Citrus bergamia Risso induces vasorelaxation of the mouse aorta by activating K(+) channels and inhibiting Ca(2+) influx. J Pharm Pharmacol. 2013;65(5):745-749.23600392
Katsuyama S, Otowa A, Kamio S, et al. Effect of plantar subcutaneous administration of bergamot essential oil and linalool on formalin-induced nociceptive behavior in mice. Biomed Res. 2015;36(1):47-54.25749150
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Morcia C, Tumino G, Ghizzoni R, Bara A, Salhi N, Terzi V. In vitro evaluation of sub-lethal concentrations of plant-derived antifungal compounds on FUSARIA growth and mycotoxin production. Molecules. 2017;22(8).28758914
Morlière P, Bazin M, Dubertret L, et al. Photoreactivity of 5-geranoxypsoralen and lack of photoreaction with DNA. Photochem Photobiol. 1991;53(1):13-19.2027902
Navarra M, Mannucci C, Delbò M, Calapai G. Citrus bergamia essential oil: from basic research to clinical application. Front Pharmacol. 2015;6:36.25784877
Navarra M, Ferlazzo N, Cirmi S, et al. Effects of bergamot essential oil and its extractive fractions on SH-SY5Y human neuroblastoma cell growth. J Pharm Pharmacol. 2015;67(8):1042-1053.25808679
Ni CH, Hou WH, Kao CC, et al. The anxiolytic effect of aromatherapy on patients awaiting ambulatory surgery: a randomized controlled trial. Evid Based Complement Alternat Med. 2013;2013:927419.24454517
Rombolà L, Amantea D, Russo R, et al. Rational basis for the use of bergamot essential oil in complementary medicine to treat chronic pain. Mini Rev Med Chem. 2016;16(9):721-728.26996621
Rombolà L, Tridico L, Scuteri D, et al. Bergamot essential oil attenuates anxiety-like behaviour in rats. Molecules. 2017;22(4).28398260
Saiyudthong S, Marsden CA. Acute effects of bergamot oil on anxiety-related behaviour and corticosterone level in rats. Phytother Res. 2011;25(6):858-862.21105176
Sakurada T, Mizoguchi H, Kuwahata H, et al. Intraplantar injection of bergamot essential oil induces peripheral antinociception mediated by opioid mechanism. Pharmacol Biochem Behav. 2011;97(3):436-443.20932858
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Sicari V. Optimization of the supercritical carbon dioxide separation of bergapten from bergamot essential oil. J AOAC Int. 2018;101(1):293-297.28762330
Verzera A, Trozzi A, Gazea F, Cicciarello G, Cotroneo A. Effects of rootstock on the composition of bergamot (Citrus Bergamia Risso et Poiteau) essential oil. J Agric Food Chem. 2003;51(1):206-210.12502409
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Young AR, Walker SL, Kinley JS, et al. Phototumorigenesis studies of 5-methoxypsoralen in bergamot oil: evaluation and modification of risk of human use in an albino mouse skin model. J Photochem Photobiol B. 1990;7(2-4):231-250.2128326
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