Berberine

Purported Benefits, Side Effects & More

Berberine

Purported Benefits, Side Effects & More
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Berberine

Common Names

  • Berberine alkaloid
  • Berberine HCl
  • Daruharidra

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.


What is it?

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.

What are the potential uses and benefits?

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.

What are the side effects?

Mild: Appetite loss, upset stomach, diarrhea, constipation, rash. Otherwise generally well tolerated.

What else do I need to know?

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

Clinical Summary

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).

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 patients with non-alcoholic fatty liver disease (9) and non-alcoholic steatohepatitis (35), berberine reduced hepatic fat and improved metabolic and lipid profiles.  Adjunctive use also reduced the risk of glycolipid metabolic disturbances in patients with schizophrenia (36) and reduced inflammatory markers in patients with acute coronary syndrome following percutaneous coronary intervention (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) (37). 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).

Data also indicate that berberine and probiotics have a synergistic hyperlipidemic effect in type-2 diabetic patients (38) (39).

Berberine was also found effective in reducing the risk of recurrence of colorectal adenoma, and may be useful as a chemopreventive following polypectom (33) (40).

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.

Purported Uses and Benefits
  • Cardiovascular support
  • High cholesterol
  • Diabetes
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).

Warnings

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).

Adverse Reactions

Mild: Anorexia, upset stomach, diarrhea, constipation, rash (9) (10) (12); otherwise generally well tolerated (6).

Herb-Drug Interactions

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).

Dosage (OneMSK Only)
References
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  2. Lan J, Zhao Y, Dong F, et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. Feb 23 2015;161:69-81.
  3. Pirillo A, Catapano AL. Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies. Atherosclerosis. Dec 2015;243(2):449-461.
  4. Wang Q, Zhang M, Liang B, et al. Activation of AMP-activated protein kinase is required for berberine-induced reduction of atherosclerosis in mice: the role of uncoupling protein 2. PLoS One. 2011;6(9):e25436.
  5. Xu J, Long Y, Ni L, et al. Anticancer effect of berberine based on experimental animal models of various cancers: a systematic review and meta-analysis. BMC Cancer. Jun 17 2019;19(1):589.
  6. Chen C, Tao C, Liu Z, et al. A Randomized Clinical Trial of Berberine Hydrochloride in Patients with Diarrhea-Predominant Irritable Bowel Syndrome. Phytother Res. Nov 2015;29(11):1822-1827.
  7. Wei W, Zhao H, Wang A, et al. A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome. Eur J Endocrinol. Jan 2012;166(1):99-105.
  8. An Y, Sun Z, Zhang Y, et al. The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment. Clin Endocrinol (Oxf). Mar 2014;80(3):425-431.
  9. Yan HM, Xia MF, Wang Y, et al. Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease. PLoS One. 2015;10(8):e0134172.
  10. Meng S, Wang LS, Huang ZQ, et al. Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention. Clin Exp Pharmacol Physiol. May 2012;39(5):406-411.
  11. Ju J, Li J, Lin Q, et al. Efficacy and safety of berberine for dyslipidaemias: A systematic review and meta-analysis of randomized clinical trials. Phytomedicine. Nov 15 2018;50:25-34.
  12. Zhang LS, Zhang JH, Feng R, et al. Efficacy and Safety of Berberine Alone or Combined with Statins for the Treatment of Hyperlipidemia: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. Am J Chin Med. 2019;47(4):751-767.
  13. Baumgartner S, Bruckert E, Gallo A, et al. The position of functional foods and supplements with a serum LDL-C lowering effect in the spectrum ranging from universal to care-related CVD risk management. Atherosclerosis. Jul 30 2020.
  14. Liang Y, Xu X, Yin M, et al. Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: a systematic literature review and a meta-analysis. Endocr J. Jan 28 2019;66(1):51-63.
  15. Asbaghi O, Ghanbari N, Shekari M, et al. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials. Clin Nutr ESPEN. Aug 2020;38:43-49.
  16. Pirro M, Francisci D, Bianconi V, et al. NUtraceutical TReatment for hYpercholesterolemia in HIV-infected patients: The NU-TRY(HIV) randomized cross-over trial. Atherosclerosis. Jan 2019;280:51-57.
  17. Marazzi G, Pelliccia F, Campolongo G, et al. Usefulness of Nutraceuticals (Armolipid Plus) Versus Ezetimibe and Combination in Statin-Intolerant Patients With Dyslipidemia With Coronary Heart Disease. Am J Cardiol. Dec 15 2015;116(12):1798-1801.
  18. Marazzi G, Campolongo G, Pelliccia F, et al. Comparison of Low-Dose Statin Versus Low-Dose Statin + Armolipid Plus in High-Intensity Statin-Intolerant Patients With a Previous Coronary Event and Percutaneous Coronary Intervention (ADHERENCE Trial). Am J Cardiol. Sep 15 2017;120(6):893-897.
  19. Marazzi G, Campolongo G, Pelliccia F, et al. Usefulness of Low-Dose Statin Plus Ezetimibe and/or Nutraceuticals in Patients With Coronary Artery Disease Intolerant to High-Dose Statin Treatment. Am J Cardiol. Jan 15 2019;123(2):233-238.
  20. Millán J, Cicero AF, Torres F, et al. Effects of a nutraceutical combination containing berberine (BRB), policosanol, and red yeast rice (RYR), on lipid profile in hypercholesterolemic patients: A meta-analysis of randomised controlled trials. Clin Investig Arterioscler. Jul-Aug 2016;28(4):178-187.
  21. Pisciotta L, Bellocchio A, Bertolini S. Nutraceutical pill containing berberine versus ezetimibe on plasma lipid pattern in hypercholesterolemic subjects and its additive effect in patients with familial hypercholesterolemia on stable cholesterol-lowering treatment. Lipids Health Dis. Sep 22 2012;11:123.
  22. Liu CS, Zheng YR, Zhang YF, et al. Research progress on berberine with a special focus on its oral bioavailability. Fitoterapia. Mar 2016;109:274-282.
  23. Cicero AFG, Fogacci F, Bove M, et al. Short-Term Effects of Dry Extracts of Artichokeand Berberis in Hypercholesterolemic Patients Without Cardiovascular Disease. Am J Cardiol. Feb 15 2019;123(4):588-591.
  24. Cicero AFG, Colletti A, Bajraktari G, et al. Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel. Nutr Rev. Sep 1 2017;75(9):731-767.
  25. Li G, Zhao M, Qiu F, et al. Pharmacokinetic interactions and tolerability of berberine chloride with simvastatin and fenofibrate: an open-label, randomized, parallel study in healthy Chinese subjects. Drug Des Devel Ther. 2019;13:129-139.
  26. Qing Y, Dong X, Hongli L, et al. Berberine promoted myocardial protection of postoperative patients through regulating myocardial autophagy. Biomed Pharmacother. Sep 2018;105:1050-1053.
  27. Chang X, Wang Z, Zhang J, et al. Lipid profiling of the therapeutic effects of berberine in patients with nonalcoholic fatty liver disease. J Transl Med. Sep 15 2016;14:266.
  28. Fan J, Zhang K, Jin Y, et al. Pharmacological effects of berberine on mood disorders. J Cell Mol Med. Jan 2019;23(1):21-28.
  29. Guo Y, Chen Y, Tan ZR, et al. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol. Feb 2012;68(2):213-217.
  30. Hou Q, Han W, Fu X. Pharmacokinetic interaction between tacrolimus and berberine in a child with idiopathic nephrotic syndrome. Eur J Clin Pharmacol. Oct 2013;69(10):1861-1862.
  31. Wu X, Li Q, Xin H, et al. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol. Sep 2005;61(8):567-572.
  32. Singh A, Zhao K, Bell C, et al. Effect of berberine on in vitro metabolism of sulfonylureas: A herb-drug interactions study. Rapid Commun Mass Spectrom. Sep 2020;34 Suppl 4:e8651.
  33. Chen YX, Gao QY, Zou TH, et al. Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study. Lancet Gastroenterol Hepatol. 2020 Mar;5(3):267-275.
  34. Adiwidjaja J, Boddy AV, McLachlan AJ. Physiologically based pharmacokinetic model predictions of natural product-drug interactions between goldenseal, berberine, imatinib and bosutinib. Eur J Clin Pharmacol. Jan 20 2022  [Online ahead of print].
  35. Harrison SA, Gunn N, Neff GW, et al. A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes. Nat Commun. 2021 Sep 17;12(1):5503.
  36. Li M, Liu Y, Qiu Y, et al. The effect of berberine adjunctive treatment on glycolipid metabolism in patients with schizophrenia: A randomized, double-blind, placebo-controlled clinical trial. Psychiatry Res. 2021 Jun;300:113899.
  37. Xie W, Su F, Wang G, et al. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022 Nov 16;13:1015045.
  38. Zhang Y, Gu Y, Ren H, et al. Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). Nat Commun. 2020 Oct 6;11(1):5015.
  39. Wang S, Ren H, Zhong H, et al. Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients: a double blinded placebo controlled randomized study. Gut Microbes. 2022 Jan-Dec;14(1):2003176.
  40. Fang S, Guo S, Du S, et al. Efficacy and safety of berberine in preventing recurrence of colorectal adenomas: A systematic review and meta-analysis. J Ethnopharmacol. 2022 Jan 10;282:114617.
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