Berberine for type 2 diabetes: meta-analysis and dosage recommendation

Highlights

Meta-analysis of 46 clinical trials involving people with type 2 diabetes
Berberine significantly improves glycemic control, blood lipid profile, inflammation, and BMI
Typical dosage is 300-500 mg, three times daily, for 3-4 months
Main side effect is digestive upset due to high dosages needed for efficacy
Low-dose dihydroberberine may be a more tolerable alternative

Summary

Study Design

This meta-analysis includes 46 randomized, controlled clinical trials involving 4,158 participants to assess the effect of berberine supplementation on blood glucose control and related metabolic factors in people with type 2 diabetes. Control interventions included placebo, lifestyle interventions (e.g., diet and exercise), or oral hypoglycemic drugs. The typical berberine dosage was 300-500 mg, three times daily, for 3 to 4 months.

Outcome Measures

Primary outcome measures included glycosylated hemoglobin (HbA1c), fasting plasma glucose, and 2-hr post-meal glucose.

Secondary outcome measures included insulin resistance as measured by fasting blood insulin and homeostasis model assessment-insulin resistance (HOMA-IR), as well as body mass index (BMI). Blood lipid profiles were also evaluated, including triglycerides, total cholesterol, LDL-cholesterol, and HDL cholesterol. Inflammation factors such as C-reactive protein, interleukin-6 and tumor necrosis factor-α were also analyzed.

Safety was assessed by monitoring serum creatinine, blood urea nitrogen, and adverse events related to the use of berberine.

Study Results

Supplementing with berberine (alone or with standard diabetic therapies) led to statistically significant improvements in glycemic control and other metabolic parameters compared to the control interventions. These improvements include the following:

Glycemic Control. Compared to control, berberine was better able to reduce HbA1c (by 0.73%), fasting blood glucose (by 15 mg/dl) and 2-hr post-meal glucose (by 23 mg/dl), as well as improve insulin sensitivity as measured by fasting blood insulin and HOMA-IR.
Blood Lipid Balance. Compared to control, berberine was better able to improve blood lipids. Greater reductions in triglycerides (by 44 mg/dL), total cholesterol (by 25 mg/dL), and LDL cholesterol (by 33 mg/dL) were reported as well as a greater increase in HDL cholesterol by 7 mg/dL.
Weight Management. Berberine was better able to support weight management with an additional 1.07-point reduction in BMI compared to control. Typically, a 1-point decrease in BMI for most adults translates to a weight loss of about 4 to 7 pounds.
Inflammatory Status. Berberine was better able than the control interventions to reduce blood levels of key markers of chronic inflammation (e.g., CRP, IL-6 and TNF-alpha).

The safety profile of berberine was favorable with no significant adverse events reported in the included trials. The main adverse event reported was digestive upset (i.e., diarrhea, bloating, and constipation).

Clinical Relevance

These findings suggest berberine (300-500 mg, three times daily) is generally safe as a complementary or alternative therapy for the treatment of type 2 diabetes.

Note: A separate pharmacokinetic study in healthy men (Moon et al., 2021) indicates low-dose (100 or 200 mg) dihydroberberine (a highly bioavailable form of berberine) raises blood berberine levels more effectively than the high-dose berberine (500 mg) typically used for glycemic control. This suggests dihydroberberine may be a more tolerable and easier-to-follow treatment choice than berberine. A summary of this study is here.

References

Guo J, Chen H, Zhang X, et al. The effect of berberine on metabolic profiles in type 2 diabetic patients: a systematic review and meta-analysis of randomized controlled trials. Oxid Med Cell Longev. 2021;2021:2074610. Full study available free at: https://pubmed.ncbi.nlm.nih.gov/34956436/

Moon JM, Ratliff KM, Hagele AM, Stecker RA, Mumford PW, Kerksick CM. Absorption kinetics of berberine and dihydroberberine and their impact on glycemia: a randomized, controlled, crossover pilot trial. Nutrients. 2021;14(1):124. Full study available free at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8746601/

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Berberine for type 2 diabetes: meta-analysis and dosage recommendation

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