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Bergamot Juice

Scientific Name(s): Citrus bergamia Risso et Poiteau
Common Name(s): Bergamot juice, Bergamot juice extract

Medically reviewed by Drugs.com. Last updated on Dec 22, 2023.

Clinical Overview

Use

Limited clinical studies have evaluated the effects of bergamot juice on dyslipidemia and cognitive function. Experiments have identified antioxidant and anti-inflammatory properties of the bergamot flavonoids, while applications in cancer and antimicrobial activity are being investigated. See also Bergamot Oil monograph.

Dosing

Cognitive dysfunction: An open-label pilot study examined the effect of bergamot-derived polyphenolic fraction (500 mg twice daily for 8 weeks as adjunctive therapy), on cognitive dysfunction in patients being treated for schizophrenia.

Dyslipidemia: Effects of bergamot-derived polyphenolic fraction on dyslipidemia have been studied at dosages of 500 mg/day and 1,000 mg/day for treatment durations of 1 month or 6 months. In a study of patients with moderate hypercholesterolemia, a standardized bergamot-derived extract (Bergavit) was given at a fixed daily dose (150 mg of flavonoids) for 6 months.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

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

Interactions

Case reports are lacking.

Adverse Reactions

Limited clinical studies in hyperlipidemia suggest bergamot juice is safe and well tolerated, although heartburn has been reported. The juice itself is bitter and unpalatable.

Toxicology

No data.

Scientific Family

Botany

The bergamot, a small tree native to tropical Asia, is cultivated extensively in Reggio Calabria, a coastal city in southern Italy, and is cultivated on a smaller scale on the Ivory Coast and in Argentina and Brazil. The trees have star-shaped white flowers with round, yellow fruits and large, dark-green, oval-shaped leaves similar to those of lemon trees. The peel of the fresh, nearly ripe fruit is the source of bergamot oil,Navarra 2015 while bergamot juice is derived from the membranous endo and mesocarp of the fruit.Giglio 2016, Mannucci 2017

Bergamot is related to bitter orange (Citrus aurantium); a synonym of C. bergamia is C. aurantium L. subspecies bergamia.Khan 2009, USDA 2017 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 teaVerzera 2003 and halva, a Middle Eastern sesame paste confection.

Bergamot juice has recently come into scientific favor, with bergamot-derived flavonoid extract being used in clinical studies. The fresh juice itself is bitter and largely unpalatable, but is available as a liqueur. Ethnobotanical reports suggest bergamot juice may have been used traditionally to treat malaria.Tagarelli 2010

Chemistry

Bergamot juice and bergamot-derived standardized preparations are characterized by the flavonoids and flavonoid glycoside content, which are distinct from other citrus fruits. Flavonoids neoeriocitrin, naringin, and neohesperidin have been identified, as well as C-glucosides, flavone and flavonone glycosides (rutin, neodiosmin, rhoifolin, and poncirin), and furanocoumarins.Gardana 2008, Mannucci 2017, Picerno 2011, Russo 2015, Salerno 2016, Toth 2016

Flavonoids brutieridin and melitidin appear to be structural analogues of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, which may provide a rationale for the observed hypolipemic properties of bergamot.Giglio 2016, Leopoldini 2010, Mannucci 2017

Uses and Pharmacology

The uses described in the following sections focus on bergamot juice specifically. See also Bergamot Oil monograph for further information regarding potential uses of C. bergamia.

Anti-inflammatory effects

Animal and in vitro data

Reduced release of proinflammatory mediators has been reported, and reduced inflammation in mouse models of colitis and in an intestinal injury/reperfusion model has been demonstrated.Impellizzeri 2015, Impellizzeri 2016, Risitano 2014, Russo 2015, Spigoni 2017

Antimicrobial effects

In vitro and in vivo data

The anti-Helicobacter pylori effect of bergamot juice has been demonstrated in clinical isolates. Synergism with antibiotics was also demonstrated.Cirmi 2016, Filocamo 2015

Antioxidant effects

Animal and in vitro data

Bergamot juice flavonoids have been shown to exert antioxidant action in various experiments. Reduced generation of reactive oxygen species and membrane lipid peroxidation, improved mitochondrial functionality, and prevention of DNA oxidative damage have been reported.DaPozzo 2018, Ferlazzo 2015, Ferlazzo 2016 Antioxidant activity may be responsible for the decreased renal injury noted in a study of hypercholesterolemic rodents.Trovato 2010

Cancer effects

In vitro data

In vitro studies have shown bergamot juice possesses antiproliferative activity.Delle Monache 2013, Ferlazzo 2016, Navarra 2014, Visalli 2014

CNS effects

Anti-inflammatory and antioxidant effects of bergamot juice have been demonstrated, which may contribute to observed CNS effects.Picerno 2011, Russo 2015

Animal data

Findings from animal models of degenerative CNS diseases suggest the flavonoids naringin and neohesperidin may attenuate cognitive impairment.Bruno 2017

Clinical data

A small, open-label pilot study examined the effect of a bergamot-derived polyphenolic fraction (500 mg twice daily for 8 weeks as adjunctive therapy) on cognitive dysfunction in 20 outpatient-managed subjects being treated for schizophrenia. Improvements from baseline measures were reported for Wisconsin Card Sorting Test perseverative errors (P=0.004) and semantic fluency test (P=0.004).Bruno 2017

Dyslipidemia

Animal data

A review of studies, conducted primarily in rats, has been published.Giglio 2016 Inhibition of HMG-CoA reductase and cholesterol biosynthesis, increases in fecal neutral sterols and total bile acids excretion, and antioxidant effects have been proposed as mechanisms of action.Giglio 2016, Leopoldini 2010, Mollace 2011, Parafati 2015 Additionally, increased lipolysis and decreased adipocyte generation were shown to be caused by influences on peroxisome proliferator-activated receptor (PPAR) levels.Lo Furno 2016

Clinical data

Limited clinical studies have evaluated the effects of bergamot juice or its extract on dyslipidemia.Giglio 2016, Mannucci 2017 Results from ongoing clinical trials are pending.Giglio 2016

In an open-label clinical study in 80 patients with moderate hypercholesterolemia, a standardized bergamot-derived extract (Bergavit) was given at a fixed daily dose (150 mg of flavonoids, with 16% neoeriocitrin, 47% neohesperidin, and 37% naringin) for 6 months. The extract increased high-density lipoprotein cholesterol (HDL-C) and decreased total plasma cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides over baseline levels.Toth 2016

A larger (N=237), double-blind, randomized, placebo-controlled trial evaluated the effect of bergamot-derived polyphenolic fraction (500 mg/day and 1,000 mg/day) among adults with hyperlipemia. Total and LDL-C and triglyceride levels were reduced, with a consequent increase in HDL. Another group of patients who had discontinued statin therapy due to adverse effects received the bergamot extract at a dosage of 1,500 mg/day; treatment in this group resulted in reductions in total cholesterol and LDL-C.Mollace 2011 Reductions in blood glucose were also reported in patients with metabolic syndrome.Giglio 2016, Mollace 2011

An open-label study (N=77) evaluated the effects of bergamot-derived polyphenolic fraction (either alone or as adjunctive therapy) on dyslipidemia. Addition of the bergamot preparation (1,000 mg orally daily) to therapy with rosuvastatin (10 mg daily) for 30 days (n=15) enhanced the efficacy of rosuvastatin.Gliozzi 2013 Similarly, in a second trial by the same researchers in patients with nonalcoholic liver steatohepatitis and metabolic syndrome (N=107), use of bergamot polyphenolic extract for 4 months produced reductions in fasting plasma glucose, serum LDL-C, and triglycerides, and an increase in HDL-C.Gliozzi 2016

Dosing

Cognitive dysfunction

An open-label pilot study examined the effects of bergamot-derived polyphenolic fraction (500 mg twice daily for 8 weeks as adjunctive therapy), on cognitive dysfunction in patients being treated for schizophrenia. The capsules contained 5 main flavonoids: neoeriocitrin, naringin, neohesperidin, melitidin, and brutieridin.Bruno 2017

Dyslipidemia

Effects of bergamot-derived polyphenolic fraction containing 28% flavonoids (principally naringin, neoeriocitrin, and neohesperidin) on dyslipidemia have been studied at dosages of 500 mg/day and 1,000 mg/day for treatment durations of 1 monthMollace 2011 or 6 months.Giglio 2016 In a study of patients with moderate hypercholesterolemia, a standardized bergamot-derived extract (Bergavit) was given at a fixed daily dose (150 mg of flavonoids, with 16% neoeriocitrin, 47% neohesperidin, and 37% naringin) for 6 months.Toth 2016

Pregnancy / Lactation

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

Naringenin and hesperetin have been shown to bind to estrogen receptors, and to inhibit the activity of aromatase (the rate-limiting enzyme in the conversion of androgens to estrogens), the clinical significance of which is unknown.Gardana 2008

Interactions

Case reports are lacking. Furanocoumarins, as found in grapefruit, are known to inhibit the metabolizing enzyme cytochrome P450 (CYP-450) 3A4, and to a lesser extent CYP1A2, 2C9, and 2D6. They may also influence the transporter P-glycoprotein. An increased bioavailability and decreased metabolism of medicines dependent on this system may be expected, with a consequent risk of toxicity.Seden 2010

Adverse Reactions

Limited clinical studies in hyperlipidemia suggest bergamot juice is safe and well toleratedMannucci 2017; heartburn was reported in a study using bergamot polyphenolic fraction (500 mg twice daily).Bruno 2017

Toxicology

Information is limited. In acute and subchronic toxicity tests in rodents, a lack of hematological and histopathological toxicity was reported.Mannucci 2017

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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Bruno A, Pandolfo G, Crucitti M, Cedro C, Zoccali RA, Muscatello MRA. Bergamot polyphenolic fraction supplementation improves cognitive functioning in schizophrenia: data from an 8-week, open-label pilot study. J Clin Psychopharmacol. 2017;37(4):468-471.28591067
Cirmi S, Bisignano C, Mandalari G, Navarra M. Anti-infective potential of Citrus bergamia Risso et Poiteau (bergamot) derivatives: a systematic review. Phytother Res. 2016;30(9):1404-11.27218799
Citrus aurantium. USDA, NRCS. 2017. The PLANTS Database (http://plants.usda.gov, December 2017). National Plant Data Team, Greensboro, NC 27401-4901 USA.
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Delle Monache S, Sanità P, Trapasso E, et al. Mechanisms underlying the anti-tumoral effects of Citrus Bergamia juice [published correction appears in PLoS One. 2018;13(10):e0206630]. PLoS One. 2013;8(4):e61484.23613861
Ferlazzo N, Cirmi S, Russo M, et al. NF-κB mediates the antiproliferative and proapoptotic effects of bergamot juice in HepG2 cells. Life Sci. 2016;146:81-91.26764233
Ferlazzo N, Visalli G, Cirmi S, et al. Natural iron chelators: Protective role in A549 cells of flavonoids-rich extracts of Citrus juices in Fe(3+)-induced oxidative stress. Environ Toxicol Pharmacol. 2016;43:248-56.27037654
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Giglio RV, Patti AM, Nikolic D, et al. The effect of bergamot on dyslipidemia. Phytomedicine. 2016;23(11):1175-1181.26851838
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