Head to head
Berberine against Bergamot
Two supplements sold for cholesterol with implausibly large reported effects and the same structural problem: small trials, concentrated in a few regions, and no outcome trial in either case.
Column A
BerberineBerberine hydrochloride
46 randomised trials show HbA1c down 0.73 percentage points, and a head to head against metformin found comparable glucose lowering. No outcome trial, mostly small single-region trials, and a third of patients get gastrointestinal side effects.
Column B
BergamotCitrus bergamia polyphenol extract
Fourteen randomised trials show large lipid changes, including LDL down 55 mg/dL. The effect sizes are implausibly large for a food extract, the trials are small and regionally concentrated, and no outcome trial exists.
Side by side, on the facts we can check
| Attribute | Berberine | Bergamot |
|---|---|---|
| Category | Metabolic | Metabolic |
| FDA status | Sold as a dietary supplement in the United States. Not approved for diabetes or any other indication. Used as a prescription antidiarrhoeal in some other countries. | Sold as a dietary supplement. Not approved to treat dyslipidaemia or anything else. |
| Half-life | Systemically short with very low oral bioavailability, under 1%, which is why it is dosed two or three times a day with meals. Active metabolites including berberrubine circulate longer than the parent compound. | Not well characterised in humans. Citrus flavanones are extensively metabolised by gut microbiota and conjugated in the liver, and plasma appearance of metabolites differs substantially between people. |
| Molecular weight | 336.4 Da as the free base, 371.8 Da as the hydrochloride. | Not a single molecule. A standardised polyphenol extract, and products differ in flavanone content, which is the main reason results may not transfer between them. |
| Mechanism | An isoquinoline alkaloid that activates AMP-activated protein kinase, which is the same node metformin acts through, largely via mild inhibition of mitochondrial complex I raising the AMP to ATP ratio. Downstream that increases glucose uptake, suppresses hepatic gluconeogenesis and reduces lipogenesis. It also upregulates LDL receptor expression by a route independent of statins, which explains the lipid effects, and alters gut microbiota composition. Oral bioavailability is very low, under 1%, so much of the effect is likely mediated in the gut and by metabolites rather than by systemic berberine. | The bergamot polyphenolic fraction is rich in flavanones, notably brutieridin and melitidin, which carry a side chain structurally similar to the statin pharmacophore. That has led to the hypothesis of partial HMG-CoA reductase inhibition, which would make it a weak statin rather than a generic antioxidant. Other proposed actions include AMPK activation and pancreatic cholesterol ester hydrolase inhibition reducing cholesterol absorption. The statin-like mechanism remains a structural inference supported by preclinical work, not something demonstrated in humans. |
| Human studies cited | 1 | 0 |
| Legal status, US | Sold as a supplement | Sold as a supplement |
Frequently asked questions
What is the difference between Berberine and Bergamot?
Berberine: 46 randomised trials show HbA1c down 0.73 percentage points, and a head to head against metformin found comparable glucose lowering. No outcome trial, mostly small single-region trials, and a third of patients get gastrointestinal side effects. Bergamot: Fourteen randomised trials show large lipid changes, including LDL down 55 mg/dL. The effect sizes are implausibly large for a food extract, the trials are small and regionally concentrated, and no outcome trial exists.
Which has stronger research evidence, Berberine or Bergamot?
This database does not grade compounds. It counts what was run in people: 1 of the 3 studies cited on the Berberine profile were human work, against 0 of 1 for Bergamot. Those counts are of our own citation lists and understate any larger literature, and neither is a recommendation.
Are Berberine and Bergamot FDA-approved?
Berberine: Sold as a dietary supplement in the United States. Not approved for diabetes or any other indication. Used as a prescription antidiarrhoeal in some other countries.. Bergamot: Sold as a dietary supplement. Not approved to treat dyslipidaemia or anything else..
Reviewed Sep 2026. This page sets two published records side by side. It is educational, it is not medical advice, and it contains no dosing protocols or recommendations for personal use.