- Berberine alkaloid
- Berberine HCl
For Patients & Caregivers
Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.
How It Works
Berberine may lower cholesterol, triglycerides, and blood sugar levels, but other interventions like lifestyle changes are also needed.
Berberine is a compound found in a variety of plant species. It is used in traditional Chinese medicine (TCM), Ayurveda, and other medicinal traditions to treat infections, digestive conditions, and inflammatory disorders. In China, it is used to help control cholesterol levels and diabetes. As a supplement, it is marketed to support healthy blood sugar, cholesterol, and triglyceride levels.
In humans, limited evidence suggests that berberine may lower cholesterol, triglycerides, and blood sugar levels. This is of particular interest because these are reversible risk factors for cardiovascular disease, and some standard treatments can cause significant side effects. An international panel of experts determined that berberine may be helpful in patients with mild cases of high cholesterol who do not tolerate statin drugs or who have metabolic syndrome. However, it is not a substitute for lifestyle changes, which are also needed to help improve cardiovascular risk factors.
Patients with these conditions should discuss appropriate therapy options with their treating physician. Well-designed trials that test safety and efficacy of berberine both singly and in combination with other treatments are warranted.
For cardiovascular support
A few studies and an expert panel suggest that berberine may be helpful for lowering some risk factors of cardiovascular disease.
To lower high cholesterol
Several studies and meta-analyses suggest benefit with berberine, but more well-designed studies are needed and the effect may be small. An expert panel suggests it may be most helpful in patients with mild cases of high cholesterol who do not tolerate statin drugs or who have metabolic syndrome.
To treat diabetes
A few studies and meta-analyses suggest that berberine may be helpful to treat diabetes, but studies are of limited quality and more studies are needed.
Do Not Take If
- You are taking bosutinib: Models predict that berberine can affect systemic concentrations of this oral chemotherapy.
- You are taking immunosuppressive drugs (tacrolimus, cyclosporin): Berberine may increase blood levels of these drugs or cause kidney toxicity.
- You are taking sulfonylureas (a type of diabetes drug): Lab studies suggest that taking berberine at the same time may affect the metabolism of these drugs, or that the metabolism of both compounds may be mutually affected. Clinical relevance has yet to be determined.
- You are taking CYP2D6, 2C9, or 3A4 substrate drugs: Berberine may decrease their effectiveness.
- You are pregnant or breastfeeding: Berberine may worsen jaundice in infants or cause a more severe condition that can lead to brain disorders.
For Healthcare Professionals
Berberine is an alkaloid constituent active in a number of plant species including barberry (Berberis vulgaris), Chinese goldthread (Coptis chinensis), goldenseal (Hydrastis canadensis), tree turmeric (Berberis aristata), and Oregon grape (Berberis aquifolium) (1). It has a deep yellow color with fluorescent properties and has long been used as a dye.
Berberine is commonly used in traditional Chinese medicine (TCM), Ayurveda, and other medicinal traditions to treat infections, diarrhea, and inflammatory disorders. In China, it is frequently used for the adjuvant treatment of type 2 diabetes, hyperlipidemia, and hypertension (2). As a supplement, it is marketed to support already normal glucose and lipid metabolism. Preclinical studies suggest antimicrobial, anti-inflammatory, antioxidant, and atheroprotective properties (3) (4), as well as potential antitumor effects (5).
In humans, preliminary data suggest some benefit for patients with irritable bowel syndrome (6) and to improve metabolic and endocrine markers in women with polycystic ovary syndrome (7) (8). In a study of patients with non-alcoholic fatty liver disease, berberine along with lifestyle intervention significantly reduced hepatic fat and improved metabolic and lipid profiles compared with lifestyle alone (9). In patients with acute coronary syndrome following percutaneous coronary intervention, adjunctive berberine significantly reduced inflammatory markers (10).
Meta-analyses evaluating trials of berberine for dyslipidemia suggest improved lipid profiles, although many studies were heterogeneous, of low quality, or had a high risk of bias (11) (12), and a review indicates the magnitude of effect to be small (13). Other meta-analyses of berberine for hyperlipidemia, hypertension, or diabetes also determined that most studies are of limited quality (2). One analysis that showed benefit in type 2 diabetic patients suggests it may be more helpful in younger patients or with short-term treatment (14), while another associated berberine with anthropometric improvements that may indirectly affect metabolic disease symptoms (15).
Berberine was also found effective in reducing the risk of recurrence of colorectal adenoma, and may be useful as a chemopreventive following polypectomy (33).
In addition, berberine has been studied in combination with other supplements. Data suggest a nutraceutical combination including berberine, red yeast rice , policosanol, astaxanthin, folic acid, and CoQ10 may lower cholesterol in HIV patients on antiretroviral therapy (16). It also improved lipid profiles in statin-intolerant patients with coronary heart disease (17) (18) (19) (20). In hypercholesterolemic patients with moderate CVD risk, another nutraceutical containing berberine and red yeast rice yielded lower LDL and triglycerides with better tolerance than with ezetimibe, but did not affect HDL (21). However oral bioavailability of berberine is considered poor (22), and monacolin K in red yeast rice has statin-like side effects, prompting the continued search for other enhanced-bioavailability berberine/nutraceutical combinations (23).
More generally, the consensus of an international lipid expert panel is that evidence for use of either a single or combination lipid-lowering nutraceutical is limited and variable, but that berberine may have benefit for prevention, particularly in patients with mild hypercholesterolemia who are statin-intolerant or have metabolic syndrome (24). In healthy subjects, berberine did not increase side effects when used in combination with simvastatin or fenofibrate (25). Additional well-designed trials that test safety and efficacy of berberine both singly and in combination with other interventions are warranted.
Mechanism of Action
Preclinical studies suggest atheroprotective effects with berberine are related to increased expression of hepatic low density lipoprotein receptor, reduced LDLR modulator proprotein convertase subtilisin/kexin type 9 (PCSK9), and improvements in endothelial dysfunction (3). In animal models, berberine exhibited statin-like effects by reducing LDL and total cholesterol levels as well as aortic lesions, and improved glucose tolerance while reducing glucose levels, weight gain, and adipose tissue (3). Other models indicate berberine may also alter hepatic metabolism-related gene expression as it is favorably located in the liver (9).
In humans, cardioprotective effects are partly attributed to reduced myocardial autophagy and apoptosis via the AMPK/mTOR pathway (26). In patients with acute coronary syndrome, berberine adjunctive to standard care reduced inflammatory markers including matrix metalloproteinase (MMP)-9, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 (10). Improvements in fatty liver disease are facilitated by decreased levels of circulating ceramides (27).
Berberine should be avoided by those who are pregnant or breastfeeding, as it may worsen jaundice in infants or result in kernicterus, a condition in which prolonged high bilirubin levels can cause irreversible effects (28).
Bosutinib: When clinically relevant doses of berberine supplements were coadministered, simulations predict a moderate 1.3-fold increase in systemic exposure to bosutinib, but not imatinib (34).
Tacrolimus: In a pediatric patient with idiopathic nephrotic syndrome, clinically relevant increases in tacrolimus concentrations and renal toxicity occurred when berberine was added to control diarrhea (30).
Cyclosporin: Berberine increased cyclosporin blood concentrations in renal transplant adults (31).
Sulfonylureas: In vitro studies indicate that berberine coadministration may compromise the metabolism of sulfonylureas or mutually affect the metabolism of both compounds (32). Clinical relevance has yet to be determined.
CYP450 substrate drugs: In human studies, repeated oral intake of berberine at a dose used in some studies significantly decreased 2D6, 2C9, and 3A4 activities (29).