# Bergamottin

**Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/bergamottin
**Data Source:** Hermetica Superfoods Ingredient Encyclopedia
**Updated:** 2026-03-20
**Evidence Score:** 2 / 10
**Category:** Compound
**Also Known As:** 5-geranoxy-7-methoxycoumarin, 5-geranyloxy-7-methoxycoumarin, BGM, 6',7'-dihydroxybergamottin precursor, citrus furanocoumarin, grapefruit compound

## Overview

Bergamottin is a natural furanocoumarin found predominantly in grapefruit juice and bergamot orange peel that exerts anticancer and enzyme-inhibitory effects. Its primary mechanism involves irreversible inhibition of cytochrome P450 3A4 (CYP3A4) in intestinal enterocytes, which significantly alters the bioavailability of numerous pharmaceutical drugs.

## Health Benefits

• Inhibits migration and invasion of glioma cells by inactivating Rac1 and downregulating MMP-9 (in vitro study, PMID: 29435067). • Induces apoptosis and G2/M arrest in lung cancer cells, though findings are limited to preclinical data (retracted study, PMID: 27222242). • Modulates miR-145/Cyclin D1 axis to inhibit melanoma growth, based on preclinical mouse studies. • Inhibits CYP3A4, increasing bioavailability of certain drugs like felodipine by up to 40% (preclinical and clinical context, no specific study cited). • Abrogates STAT3 activation in multiple myeloma cells, enhancing apoptosis (animal studies, PMID: not in excerpt).

## Mechanism of Action

Bergamottin acts as a mechanism-based, irreversible inhibitor of the CYP3A4 enzyme by forming a reactive intermediate that covalently binds to the enzyme's active site, effectively blocking first-pass [metabolism](/ingredients/condition/weight-management) of many drugs in intestinal epithelial cells. In preclinical cancer models, it suppresses glioma cell migration by inactivating the Rho GTPase Rac1 and downregulating matrix metalloproteinase-9 (MMP-9), disrupting the cytoskeletal remodeling required for invasion. Additionally, it modulates the miR-145/Cyclin D1 axis, inducing G2/M cell cycle arrest and promoting apoptosis in lung and other cancer cell lines via mitochondria-mediated caspase activation.

## Clinical Summary

The vast majority of bergamottin research is preclinical, conducted in vitro using human cancer cell lines (glioma, lung, breast) or in animal pharmacokinetic models, with no robust human clinical trials specifically on isolated bergamottin supplementation to date. In vitro studies, such as PMID 29435067, demonstrated inhibition of glioma cell migration and invasion, though these findings have not been replicated in human subjects. Notably, at least one cited study on its apoptotic effects in lung cancer cells (PMID 27222242) has been retracted, substantially weakening the evidence base in that area. Its drug-interaction effects via CYP3A4 inhibition are the best-characterized pharmacological action and are supported by well-replicated pharmacokinetic data from grapefruit juice interaction studies.

## Nutritional Profile

Bergamottin is a natural furanocoumarin compound, not a food ingredient with conventional macronutrient or micronutrient content. It is a lipophilic secondary metabolite primarily classified as a bioactive phytochemical. Key compositional data: Bergamottin (5-geranyloxy-7-methoxycoumarin, CAS 7380-40-7) is found in grapefruit juice at approximate concentrations of 2–23 mg/L in fresh grapefruit juice, with higher concentrations in the peel oil (estimated 0.5–1.5 mg/g in grapefruit peel extract). It is also present in bergamot essential oil (Citrus bergamia) at trace-to-moderate levels, as well as in pomelo and certain lime varieties. As a furanocoumarin, it contains no meaningful caloric value, protein, fat, carbohydrate, fiber, vitamins, or minerals in the quantities typically encountered. Its primary characterization is as a potent irreversible inhibitor of cytochrome P450 3A4 (CYP3A4) and CYP1A2 enzymes, with an IC50 for CYP3A4 inhibition reported at approximately 0.16–0.8 µM in vitro. Bioavailability is limited due to its lipophilic nature (logP approximately 4.5); oral absorption is moderate, with rapid first-pass [metabolism](/ingredients/condition/weight-management). It is typically encountered as a minor constituent within whole grapefruit products rather than as an isolated nutritional compound, and dietary intake from normal grapefruit consumption ranges from approximately 1–20 mg per serving depending on preparation method and cultivar.

## Dosage & Preparation

Preclinical studies used IP doses of 25-100 mg/kg in animal models. Oral doses of 6-12 mg have been noted to increase felodipine bioavailability in human contexts. Consult a healthcare provider before starting any new supplement.

## Safety & Drug Interactions

Bergamottin's most clinically significant safety concern is its potent inhibition of intestinal CYP3A4, which can dramatically increase plasma concentrations of drugs such as statins (simvastatin, atorvastatin), calcium channel blockers (felodipine), immunosuppressants (cyclosporine), and certain benzodiazepines, raising the risk of toxicity. Individuals taking any CYP3A4-metabolized medication should avoid bergamottin-containing supplements or high-volume grapefruit juice consumption without physician guidance. Phototoxicity is a known class effect of furanocoumarins; topical exposure combined with UV radiation can cause skin burns and hyperpigmentation. Safety data during pregnancy and lactation are absent, and supplemental use should be avoided in these populations as a precautionary measure.

## Scientific Research

There are no human clinical trials or meta-analyses for bergamottin; research is limited to in vitro and animal studies. For example, a study on glioma cells (PMID: 29435067) showed inhibited cell migration, and a retracted mouse study (PMID: 27222242) initially reported tumor weight reduction.

## Historical & Cultural Context

Bergamottin itself has no documented historical or traditional uses; it is primarily a component of grapefruit juice, which is traditionally consumed for its nutritional and flavor properties.

## Synergistic Combinations

Grapefruit extract, bergamot oil, felodipine, other furanocoumarins, [antioxidant](/ingredients/condition/antioxidant)-rich foods

## Frequently Asked Questions

### What is bergamottin and where does it come from?

Bergamottin is a linear furanocoumarin compound found at high concentrations in the peel oil and juice of grapefruit (Citrus paradisi) and bergamot oranges (Citrus bergamia), as well as in smaller amounts in other citrus fruits. It is one of the primary compounds responsible for the well-documented 'grapefruit juice effect,' in which CYP3A4 enzyme activity in the gut wall is inhibited, altering drug absorption.

### Does bergamottin interact with medications?

Yes, bergamottin irreversibly inhibits intestinal CYP3A4, an enzyme that metabolizes roughly 50% of pharmaceuticals including statins, calcium channel blockers, and immunosuppressants. This can raise plasma drug levels 2- to 15-fold, substantially increasing the risk of adverse effects and toxicity. Patients on any CYP3A4-metabolized drug must consult their physician before using bergamottin-containing products.

### Can bergamottin kill cancer cells?

Preclinical in vitro studies suggest bergamottin can inhibit cancer cell proliferation and induce apoptosis via Rac1 inactivation, MMP-9 downregulation, and modulation of the miR-145/Cyclin D1 pathway in glioma and lung cancer cell lines. However, no human clinical trials have confirmed these effects, and at least one key lung cancer study (PMID 27222242) has been retracted, significantly limiting current evidence. These findings should not be interpreted as evidence that bergamottin treats or prevents cancer in humans.

### Is bergamottin the same as bergamot extract?

No, bergamottin is a single furanocoumarin molecule isolated from bergamot and grapefruit, whereas bergamot extract is a complex mixture containing polyphenols such as brutieridin, melitidin, naringenin, and neoeriocitrin, which are studied primarily for cholesterol-lowering effects. Standardized bergamot polyphenol fraction (BPF) supplements typically contain little to no bergamottin and have a distinct mechanism of action involving HMGR enzyme modulation. Confusing the two can lead to incorrect expectations about benefits and risks.

### What is the safe dosage of bergamottin?

No established safe or effective dosage for isolated bergamottin supplementation in humans has been determined, as no phase I or II clinical dose-finding trials have been published. Typical grapefruit juice (200–250 mL) contains approximately 0.04–3.7 mg/L of bergamottin, and even these dietary amounts are sufficient to cause clinically significant CYP3A4 inhibition lasting up to 24 hours. Until human safety and efficacy data are available, supplemental bergamottin should be approached with extreme caution, particularly in individuals on any prescription medication.

### What does current research show about bergamottin's effectiveness against cancer?

Most bergamottin cancer research is limited to laboratory and animal studies, showing promise in inhibiting glioma cell migration, inducing lung cancer cell apoptosis, and suppressing melanoma growth through specific molecular pathways. However, these preclinical findings have not been confirmed in human clinical trials, and at least one key lung cancer study has been retracted, meaning bergamottin cannot currently be recommended as a cancer treatment. Human research is needed before any clinical claims can be substantiated.

### Who should avoid bergamottin supplements due to its effects on drug metabolism?

People taking medications metabolized by the CYP3A4 enzyme—including certain statins, immunosuppressants, antihistamines, and blood pressure medications—should avoid bergamottin, as it inhibits this enzyme and can dangerously elevate drug levels in the bloodstream. Pregnant and nursing women should also avoid bergamottin due to insufficient safety data. Anyone on prescription medications should consult their healthcare provider before using bergamottin supplements.

### What forms of bergamottin are available and how do they differ in effectiveness?

Bergamottin is primarily available as part of whole bergamot extract (containing other furanocoumarins and compounds) or as an isolated/concentrated bergamottin supplement. Whole bergamot extract may provide synergistic effects from multiple compounds, while isolated bergamottin allows for standardized dosing but lacks the potential benefits of other extract constituents. Bioavailability and cellular effects may differ between forms, though direct comparative human studies are lacking.

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*Source: Hermetica Superfoods Ingredient Encyclopedia — https://ingredients.hermeticasuperfoods.com*
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