Berberine: The Supplement Being Called Nature's Metformin
Berberine is a plant alkaloid widely used for conditions from gastrointestinal infections to diabetes and high cholesterol,6 and it has attracted attention as a metabolic and potential longevity supplement. In a small 2008 trial, its effect on blood sugar in newly diagnosed type 2 diabetes was similar to metformin's over 3 months.3 Here is what the human evidence shows, and where it stops.
- In laboratory studies, berberine regulates glucose and lipid metabolism, and in liver cells it lowers PCSK9, a protein that removes LDL receptors.3,4 These are lab findings; how much they explain its effects in people is not known.
- In a 2008 pilot study, berberine lowered blood sugar about as much as metformin over 3 months in 36 adults with newly diagnosed type 2 diabetes.3 A 2015 meta-analysis of 27 trials with 2,569 patients found that berberine with lifestyle changes lowered fasting and after-meal glucose and HbA1c more than lifestyle changes alone or placebo.5
- For cholesterol, berberine added to lipid-lowering drugs lowered total and LDL cholesterol more than the drugs alone, and on its own it performed similarly to those drugs for these measures.5 In liver cells it reduced PCSK9, which may explain part of the effect.4
- Berberine changes how the liver processes other drugs: two weeks of 300 mg three times a day reduced the activity of the enzymes CYP2D6, CYP2C9 and CYP3A4 in healthy volunteers.6
- Key gaps: the trials summarized here measured blood sugar and cholesterol, not heart attacks, strokes or survival, and in the 2008 pilot study about a third of patients had temporary gastrointestinal side effects.3
Berberine is an alkaloid found in several plants, including barberry (Berberis vulgaris), and has been studied for uses ranging from diabetes, heart disease and high cholesterol to inflammation and infections.1 Modern interest in berberine for metabolic health grew from trials in China comparing it with metformin.3
Mechanisms of Action
Most of what is known about how berberine works comes from cell and animal studies. It regulates glucose and lipid metabolism in those models,3 and in human liver cells it lowered PCSK9, a protein that breaks down LDL receptors; combined with a statin, it raised LDL receptor levels while blunting the statin-driven rise in PCSK9.4 Berberine is often described as activating AMPK, the energy sensor also activated by metformin and exercise, whose roles have been mapped largely in genetically modified animals.2
The Human Evidence: Glucose and Insulin
The most cited berberine trial is a 2008 pilot study by Yin and colleagues. In its first part, 36 adults with newly diagnosed type 2 diabetes were randomized to berberine or metformin, 0.5 g three times a day for 3 months; berberine's effect on blood sugar was similar to metformin's, with HbA1c falling from 9.5% to 7.5% and fasting glucose from 10.6 to 6.9 mmol/L.3 In the second part, 48 adults with poorly controlled diabetes added berberine for 3 months: HbA1c fell from 8.1% to 7.3%, and fasting insulin and HOMA-IR fell by 28.1% and 44.7%.3 About a third of patients (34.5%) had temporary gastrointestinal side effects.3
A 2015 meta-analysis of 27 randomized trials with 2,569 patients found that, in type 2 diabetes, berberine with lifestyle changes lowered fasting and after-meal glucose and HbA1c more than lifestyle changes alone or placebo, and no serious adverse reactions were reported.5 These trials measured blood sugar and cholesterol rather than heart attacks, strokes or survival.
Lipid Effects: A Distinct Mechanism
For cholesterol, the same meta-analysis found that berberine with lifestyle changes beat lifestyle changes alone, and berberine with lipid-lowering drugs beat the drugs alone for total and LDL cholesterol. Compared head to head with lipid-lowering drugs, berberine was similar for total and LDL cholesterol and better for triglycerides and HDL cholesterol.5 In liver cells, berberine lowered PCSK9, and the authors of that study suggested it may be a useful supplement to statin treatment; that has not been tested in outcome trials.4
Dosing, Bioavailability, and Safety
The trials described here used 0.5 g three times a day3 or 300 mg three times a day.6 In the 2008 pilot study, 34.5% of patients had temporary gastrointestinal side effects,3 and the 2015 meta-analysis found no serious adverse reactions across 27 trials.5 This guide does not recommend a dose; discuss any supplement with your clinician.
Berberine affects drug metabolism. In healthy volunteers, two weeks of berberine (300 mg three times a day) reduced the activity of the liver enzymes CYP2D6, CYP2C9 and CYP3A4; for example, exposure to midazolam, a drug cleared by CYP3A4, rose by about 40%.6 Because many medicines are cleared by these enzymes, anyone taking other medications should check for interactions with a pharmacist before starting berberine.
For type 2 diabetes, berberine is not a substitute for prescribed treatment, and any change should be discussed with a clinician. For people without diabetes, the trials summarized here did not test long-term health or longevity outcomes.
Put this research into practice: Supplement Evidence Database · Supplement Interaction Checker
References
- 1Imenshahidi M, Hosseinzadeh H. "Berberis Vulgaris and Berberine: An Update Review." Phytother Res. 2016;30(11):1745-1764. PubMed · DOI
- 2Viollet B, et al. "AMPK: Lessons from transgenic and knockout animals." Front Biosci (Landmark Ed). 2009;14(1):19-44. PubMed · DOI
- 3Yin J, et al. "Efficacy of berberine in patients with type 2 diabetes mellitus." Metabolism. 2008;57(5):712-7. PubMed · DOI
- 4Cameron J, et al. "Berberine decreases PCSK9 expression in HepG2 cells." Atherosclerosis. 2008;201(2):266-73. PubMed · DOI
- 5Lan J, et al. "Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension." J Ethnopharmacol. 2015;161:69-81. PubMed · DOI
- 6Guo Y, et al. "Repeated administration of berberine inhibits cytochromes P450 in humans." Eur J Clin Pharmacol. 2012;68(2):213-7. PubMed · DOI
