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Berberine

Berberine is a alkaloid extracted from a variety of herbs. It is supplemented for its anti-diabetic effects, which rival the potency of some pharmaceuticals, though still require more research for a proper comparison.

Our evidence-based analysis on berberine features 329 unique references to scientific papers.

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Summary of Berberine

Primary information, health benefits, side effects, usage, and other important details

What is berberine?

Berberine is an alkaloid extracted from various plants used in traditional Chinese medicine. It's primarily used to reduce insulin resistance and improve biomarkers of type II diabetes such as fasting glucose and glycated hemoglobin. Berberine can activate an enzyme called Adenosine Monophosphate-Activated Protein Kinase (AMPK) while inhibiting Protein-Tyrosine Phosphatase 1B (PTP1B), thus increasing insulin sensitivity. Other possible mechanisms of action include protecting and β-cells, regulating hepatic gluconeogenesis, and reducing inflammatory cytokine signaling.

What are the benefits of berberine?

Human and animal research suggests that 1500mg of berberine, taken in three doses of 500mg each, is equally effective as taking 1500mg of metformin or 4mg glibenclamide, two pharmaceuticals for treating type II diabetes. Effectiveness was measured by how well the drugs reduced biomarkers of type II diabetes. It should be noted that although there's a fair bit of research suggesting strong effects of berberine for reducing biomarkers of type II diabetes, it's is still less supported by research than many pharmaceuticals and it's unclear what its long-term effects on mortality and complications are.

Some evidence suggests that it can reduce LDL-cholesterol and triglycerides in type II diabetics, and possibly lead to a small increase in HDL-cholesterol.

What are berberine's side-effects and drawbacks?

Berberine has a high potential to interact with medications, and some interactions may be severe. It is generally safe in normal doses, but more long-term research on its safety is needed. Gastrointestinal upset can occur when high doses are used, and due to its ability to reduce blood sugar, it may increase the risk for hypoglycemia in high doses, though this isn't a common occurance.

Is berberine safe to take?

Tentatively, yes, but a doctor's guidance is highly recommended. Berberine has been the subject of much research and seems to be potent like many pharmaceuticals, but unlike the most well-researched pharmaceuticals, its long-term safety and frequent adverse effects haven't been sufficiently evaluated.

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How to Take

Medical Disclaimer

Recommended dosage, active amounts, other details

The standard dose of berberine is 900-2,000mg a day, divided into three to four doses.

Berberine should be taken with a meal, or shortly after, to take advantage of the blood glucose and lipid spike associated with eating.

Too much berberine at once can result in stomach upset, cramping, and diarrhea.

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Human Effect Matrix

Unlocked for Examine members

The Human Effect Matrix summarizes human studies to tell you what effects Berberine has on your body, how much evidence there is, and how strong these effects are.

Full details are available to Examine members.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-b Strong Very High See all 4 studies
The usage of berberine in reducing blood glucose, according to the most recent meta-analysis, is comparable to the oral hypoglycemic drugs Metformin or Glibenclamide; this suggests berberine is one of the more effective supplements for blood glucose reductions.
grade-b Strong Very High See all 3 studies
The reduction of HbA1c associated with berberine, according to a meta-analysis of diabetics using 1,000-1,500mg berberine daily, was −0.72% (95% CI −0.97 to −0.47) more than placebo. This reduction appears to be one of the more significant reductions associated with dietary supplements.
grade-b Notable Very High See all 4 studies
Total cholesterol appears to be decreased by around −0.58mmol/L (95% CI −1.02 to −0.14), which is not overly potent. The reduction in notable as if this mechanism is via PCSK9 inhibition then it would work very well with statin drugs.
grade-b Minor Very High See all 4 studies
Degree of improvement was 0.07mmol/L (95% CI 0.04 to 0.10) according to the meta-analysis, not remarkably effective
grade-b Minor Very High See all 4 studies
Degree of reduction of fasting insulin according to meta-analysis was SMD −0.50mU/L (95% CI −0.96 to −0.03) which is not overly remarkable.
grade-b Minor Very High See all 3 studies
The reduction of LDL-C when berberine was paired with lifestyle changes was −0.58mmol/L (95% CI −0.78 to −0.39) in diabetics, suggesting a significant benefit but not remarkably potent. However, another study in people with nonalcoholic fatty liver disease showed no benefit over lifestyle changes alone.
grade-b Minor Very High See all 5 studies
Degree of reduction according to meta-analysis was −0.48mmol/L (95% CI −0.57 to −0.39) which was not overly remarkable.
grade-c Minor - See study
Was able to reduce canker sores when topically applied, but was not compared to a reference compound.
grade-c Minor - See study
A positive effect, but the potency thereof was not overly remarkable
grade-c Minor - See all 3 studies
One study in people with NAFLD has shown mild increases in HOMA-IR when berberine is added to lifestyle changes compared to lifestyle changes alone.
grade-c Minor - See study
Minor effect in persons with cardiomyopathy, but it is unsure if berberine has a per se benefit on quality of life.
grade-d Minor - See study
One study showed a slight decrease in systolic blood pressure only in people with the metabolic syndrome who were given berberine 0.5g three times a day for three months.

Studies Excluded from Consideration

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Frequently Asked Questions and Articles on Berberine

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Things to Note

Is a Form Of

Primary Function:

Do Not Confuse With

Piperine (Black Pepper extract), Berberol (Brand name), Berberrubine (Metabolite)

Goes Well With

  • P-glycoprotein (P-Gp) inhibitors increase absorption rate, with Milk Thistle demonstrated in humans and Stephania tetrandra being promising

  • Sodium caprate (increases absorption, not related to P-Glycoprotein)

  • Atrogin-1 inhibition (theoretically reverses the possible degradation of lean mass associated with AMPK activation into synthesis)

Caution Notice

Known to interact with enzymes of Drug Metabolism. Also may interact with microlide antibiotics such as azithromycin and clarithromycin at hERG channels on the heart, leading to serious cardiotoxicity.

  • High doses of berberine taken acutely, due to their poor intestinal uptake rate, may cause cramping and diarrhea; for this reason, berberine should be taken in multiple doses throughout the day

  • Berberine is known to inhibit CYP2D6, CYP2C9, and CYP3A4, which can lead to a host of drug interactions, some of which can be serious

  • Berberine is known to induce the protein concent of P-glycoprotein

  • Berberine interacts with organic anion transporter proteins, which may limit tissue uptake of metformin

  • Berberine may interact with microlide antibiotics such as azithromycin and clarithromycin at hERG channels on the heart, leading to serious cardiotoxicity

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