In people with preexisting conditions that are related to metabolism (e.g., type II diabetes, PCOS, CVD, metabolic syndrome, NAFLD), berberine could potentially induce weight loss (as measured through BMI, body weight, waist circumference, and waist to hip ratio).^{[5][8][4][25]} However, the few studies in otherwise healthy participants did not echo these findings.^[26][25] Given the mechanisms by which berberine acts on metabolism, this might point to weight loss merely being a function of berberine’s regulation of metabolic factors, such as a decrease in the genes responsible for the body’s production of lipids and/or an increase in stored fatty tissue being used for energy.^[18] If so, then berberine may not be useful for weight loss in those without the matching genetic predisposition, since, for example, not all people who want to lose weight will meaningfully underexpress genes for fatty acid metabolism. While preclinical evidence on berberine for weight loss in those with metabolically related conditions is promising, the clinical evidence is still lacking in overall quality and consistent findings.^[7]

The largest body of evidence for berberine in reproductive health is as a treatment for people with PCOS.^[27][4][7] Some research has been done on berberine’s effects on uterine fibroids^[28], premature ovarian failure,^[29] and dysmenorrhea,^[30] but these studies are few and/or still in preclinical phases. In people with PCOS, clinical evidence suggests that berberine, at doses ranging from 300 mg/d to 2000 mg/d, may be beneficial for pregnancy and/or conception: when compared with placebo or no treatment at all, berberine may aid in reducing of testosterone and the ratio of LH to FSH.^[4] It is unclear, however, whether this is a direct effect or simply a result of berberine’s impact on other factors such as glucose and blood lipid regulation.^[4][7] Another point worth consideration is that it does appear that higher doses of berberine are more prone to adverse events, and there simply is not enough evidence available to confirm the safety of berberine in (or surrounding) pregnancy.^[7]

A more recent topic of exploration has been berberine’s immune modulation through reductions in inflammatory biomarkers (IL-6, IL-1-beta, CRP, and TNF-α) generally in those already with some form of metabolic distress (diabetes, metabolic syndrome, cardiovascular disease).^{[31][5][8][32][3]} In another apparent connection between berberine and immune health, three recent studies suggest that berberine (0.3-0.6 g/d) could reduce recurrence of colorectal polyps in those with a history of colorectal cancer, when compared to placebo controls.^[9] Though more recent results may be a bit more promising, caution is warranted since there are still some concerns over the quality (and sometimes quantity) of the studies producing the findings.^[7]

Some of the longest-standing research on berberine’s health effects concerns its use as an antimicrobial.^[2][3] Berberine has mixed results when studied for its properties as an antiviral (HIV, coronaviruses, influenza), antibacterial (H. pylori, V. cholerae, S. aureus), and even as an antifungal. Taking this body of evidence into account, berberine’s best use as an antimicrobial seems to be as an adjunctive or combination therapy.^[33][3][34]

Broadly speaking, berberine supplementation results in the activation of enzymes responsible for regulating (among other things) energy usage in the body. Most notably, berberine activates AMPK, PKC, and SIRT 1.^[13]

In animal models, berberine supplementation results in the activation of AMPK.^[12] When active, AMPK interacts with a variety of enzymes to suppress anabolic processes (i.e., storing energy and building tissue) and promote catabolism (i.e., breaking down the aforementioned tissue and utilizing glucose for energy).^[14] As well as increasing the activity of the glycolytic pathway, AMPK also improves glucose uptake by cells by encouraging glucose transport proteins to migrate to the cell membrane, which increases the rate at which glucose exits the blood and enters the cells (where it is broken down).^[15]

Relatedly, berberine also results in the activation of PKC. Like AMPK, PKC has a variety of regulatory functions, but most importantly (in this case) it regulates the expression of insulin receptor genes. When activated, PKC increases the rate at which these genes are transcribed and translated into proteins, thereby increasing the number of insulin receptors on cell membranes.^[16] Insulin is required to transport glucose into muscle and fat cells, so this PKC-dependent upregulation of insulin receptors can be said to make these cells more “insulin-sensitive”, meaning that less insulin must be released by the pancreas to effectively move glucose from the blood into cells.

Berberine can also improve insulin sensitivity through its effects on another regulatory enzyme, SIRT1. SIRT1 is one of several sirtuins present in mammals and helps regulate apoptosis (programmed cell death), mitochondrial function, and inflammation. One animal study found that berberine’s activation of SIRT1 helps improve mitochondrial function (in part by increasing the synthesis of mitochondria) and consequently lowers blood sugar and reduces obesity in rats fed a high-fat diet.^[17]

As mentioned in the section above, berberine activates AMPK, which (among other things) suppresses the synthesis of lipids while promoting their breakdown, leading to a net reduction of their concentration in the blood.^[13][18]

Alongside its AMPK-dependent effects, berberine additionally benefits blood lipids by increasing the abundance of low-density lipoprotein receptors (LDLR). While it doesn’t increase expression of LDLR, it does increase the stability of the mRNA transcripts that go on to become LDLR proteins, which increases the abundance of LDLR receptors in cells and increases the rate at which they remove LDL cholesterol from the blood.^[19] Additionally, berberine also lowers cholesterol by interfering with its absorption in intestines and its release into the blood.^[20]

One noteworthy thing that berberine doesn’t do is interfere with cholesterol synthesis in the body. This contrasts with the most common class of cholesterol-lowering medications, statins, which directly inhibit the rate-determining enzyme of cholesterol synthesis, HMG-CoA reductase.^[19] Because its mechanism of action is distinct from that of statins, it means berberine has potential to be useful either in conjunction with, or as a replacement for, statins. Current clinical studies on this topic, while hopeful, are still unclear, due to inconsistent findings across the body of evidence.^[3][21][22]

In a similar vein, perhaps through its influence on blood lipids (or perhaps via effects on inflammation), berberine shows some promise as an antihypertensive when used as an add-on to standard of care treatments.^[23] There are few good-quality clinical studies on this topic though, so more evidence is needed.^[24]