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.

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.

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.

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.

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.

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects berberine has on your body, and how strong these effects are.

Grade	Level of Evidence [show legend]
	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
	Blood Glucose	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.
	HbA1c	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.
	Total Cholesterol	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.
	HDL-C	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
	Insulin	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.
	LDL-C	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.
	Triglycerides	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.
	Canker Sores	Minor	- See study	Was able to reduce canker sores when topically applied, but was not compared to a reference compound.
	Exercise Capacity (with Heart Conditions)	Minor	- See study	A positive effect, but the potency thereof was not overly remarkable
	Insulin Sensitivity	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.
	Quality of Life	Minor	- See study	Minor effect in persons with cardiomyopathy, but it is unsure if berberine has a per se benefit on quality of life.
	Blood Pressure	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

• Confounded with other nutraceuticals^[1]

• Specifically, confounded with Policosanol and Red Yeast Extract^[2][3][1]