Berberine in Diabetes
It seems the search for novel therapies in diabetes is a never-ending quest. Just as new heroes are found, old stalwarts are discovered to have health risks of their own and become relegated to out-of-print medical textbooks. Frustrating as this is for researchers, many patients also know therapies simply quit being effective for them over time. Given the challenging nature of finding effective therapies, researchers continue to explore the plant world for glucose-lowering agents that have few side effects and might offer therapeutic longevity.
In recent years, the herbal compound berberine has been explored as a possible therapy in diabetes. Berberine-containing herbs such as Goldenseal (Hydrastis canadensis) and Oregon Grape (Berberis aquifolium) are readily available on the US Market, and are most commonly marketed for immune enhancement, antibacterial and antiparasitic effects, and gastrointestinal health (largely owing to the antimicrobial effects). The Chinese herb Coptis chinensis is also a significant source of berberine, though it is less widely known in the US. Most of the studies on berberine for diabetes have been conducted in China, and have consequently used extracts from Coptis. Few US manufacturers market any of the berberine-containing herbs for blood sugar control.
How Might it Work?
Laboratory studies typically involving rodent studies or cultured human cells have found a number of possible mechanisms for the beneficial effects of berberine on blood sugar control. Several studies have found berberine leads to an upregulation of insulin receptor activity, while other trials also found effects on blood sugar may be related to berberine’s antimicrobial effects.
Researchers in China have studied berberine’s effects on different types of human cells, including liver, colon, immune, and pancreas cells. They have consistently found increased insulin receptor expression and glucose metabolism in these cell lines. 1,2 Further supporting an insulin receptor-related mechanism was the finding that rats with type 2 diabetes (associated with reduced insulin sensitivity) had improvements in their blood sugar, but rats with type 1 diabetes (a deficiency of insulin) had minimal change in their blood glucose after treatment with berberine.
Another hypothesis, with some early supporting evidence, is that berberine’s glucose-lowering effect might be related to activity in the gut. One small trial in animal models of diabetes found berberine led to a decreased activity of the sugar-digesting enzymes located in the cells of the intestinal wall.3 Another group has hypothesized berberine’s favorable effects on blood sugar may be a side effect of its antimicrobial effects. They hypothesize berberine may kill off certain intestinal bacteria that contribute to increased inflammation and insulin resistance.4
Clinical Trials of Berberine in Diabetes
It seems clear berberine has a significant blood glucose-lowering effect, whatever the mechanism (or, more likely, mechanisms) may be. Several clinical trials have now been conducted to examine how much berberine lowers glucose in humans, as well as to assess overall safety and tolerability. These early studies have found berberine is as potent as other medications for diabetes, and may also lower cholesterol and improve blood flow beneficial effects most diabetes drugs don’t have. Granted, the available research is limited, and the results may not be generalizable to people in the United States. Regardless, the findings to date are provocative.
In a randomized trial of 116 patients with newly-diagnosed with type 2 diabetes, Yifou Zhang et. al. examined the effects of berberine (500mg, twice daily) compared to placebo.5 After three months, study participants receiving berberine had significant reductions in hemoglobin A1c (HbA1c, reducing from 7.5% to 6.6%), total cholesterol, LDL-cholesterol, triglycerides, and systolic blood pressure. Of 57 people in the berberine group, five reported constipation and two of these had to reduce their dose to 250mg, twice daily. No other adverse effects were reported.
Yin’s research group reported on two clinical trials in the same paper.6The first trial compared berberine (500mg, three times daily) to metformin in 36 newly-diagnosed patients. After thirteen weeks, berberine performed as well as metformin in reducing HBA1c, but had beneficial effects on total cholesterol and triglycerides (though not LDL or HDL) that metformin did not exhibit. This group’s second trial added berberine to conventional care in 48 patients with poorly-controlled type 2 diabetes, and found berberine reduced HBA1c over the thirteen week study period (from 8.1% to 7.3%), as well as improved insulin sensitivity and lipid status. Adverse effects included mild gastrointestinal symptoms, which typically resolved after dose reduction.
Hao Zhang et. al. completed a three-armed trial of a commercially available berberine product compared to metformin and rosiglitazone.2 In this two-month trial of 97 patients with type-II diabetes, Zhang’s group found berberine reduced HBA1c comparable to rosiglitazone (from 8.3% to 6.8% after two months, values true for both groups). Oddly, the metformin group started with a much higher HBA1c (9.4%), which reduced to 7.2% during the trial period. Apart from its glucose-lowering effects, berberine also reduced triglycerides much greater extent than either rosiglitazone or metformin. The researchers reported no significant adverse effects in any of the patients treated with berberine.
In 2010, Hao Zhang’s group also reported on a smaller trial of 35 patients with diabetes and either hepatitis B (HBV) or hepatitis C (HCV).2 After successfully treating their diabetes with berberine (1000mg/day) for two months, the berberine group also had lower levels of enzymes from the liver (higher liver enzymes are associated with worse disease in hepatitis). These findings are especially exciting because several medications used to treat diabetes may cause liver toxicity and are used cautiously in people with diabetes patients with concurrent liver disease. If further research supports the safety of berberine in people with liver disease, it may become a regular part of care for people suffering from both diabetes and hepatitis.
Other Beneficial Effects
Diabetes does not typically exist in isolation. Many patients with diabetes may also have cardiovascular problems, high blood pressure, or high cholesterol.
As has been noted in the above trials, berberine seems to have regular success at improving cholesterol status. Several other clinical trials have been conducted supporting berberine’s role as a lipid-lowering agent. Affuso’s group found, when combined with 200mg of red yeast rice, 500mg of berberine led to significant reductions in total cholesterol, LDL, and triglycerides after a six-week trial.7 Kong’s group found berberine added to the medication simvastatin achieved greater lipid-lowering effects than simvastatin alone (reaching a total of 31.8% reduction in serum LDL).8
Vascular health also seems to be improved by berberine. The afore-mentioned study by Affuso et. al. also found notable benefits from berberine on the ability of the blood vessels to dilate with increases in blood flow (called “flow-mediated vasodilation”).7 Another group tracked the effects of 1200 grams of berberine on 14 healthy subjects over one month, and also found improvements in flow-mediated vasodilation.9
Concerns and Side Effects
Nearly all treatments whether pharmaceutical or herbal have potential side effects. The most commonly found adverse effects of berberine seem to be gastrointestinal in nature, and these tend to be transient and responsive to dose reductions.
The potential for drug-drug interactions is of greater concern because berberine shares the same metabolic enzymes in the liver with numerous medications. Depending on the exact medication, this interaction can lead to increased or decreased levels of the medications. In some circumstances, this can lead to dose reductions in medications, or of berberine. However, it can also increase medication side effects. Please discuss all of your medications and supplements with your physician and/or pharmacist, and find a qualified source for health information related to herbal medicines (e.g., naturopathic physicians, integrative medical doctors or nurse practitioners, or licensed herbalists).
Although additional clinical trials are needed on berberine in the United States, the available clinical trials support berberine for blood sugar and cholesterol-lowering, combining it with other medications may lead to a dangerous lowering of blood sugar. In addition, the effect of berberine on the breakdown of other medications is an additional reason to be conservative. Finally, be sure you’re purchasing from a trusted source that can answer questions regarding the source of the berberine and has quality-certified manufacturing processes. Contaminated supplements, or supplements that don’t contain what they claim to, are more expensive in their health consequences than paying a few dollars more for a supplement from a trusted source.
Rather than treating this compound as a simple over-the-counter remedy to be safely added to any diabetes regimen, you should discuss with your naturopathic physician or other licensed healthcare provider whether berberine may be a helpful therapy in managing your diabetes.
And, as always, the best ways to get your blood sugar under control don’t come in a bottle they involve the tried-and-true approach of a sensible diet and regular exercise.
Ryan Bradley, ND, MPH and Bill Walter, ND April, 2012
Kong WJ, Zhang H, Song DQ, et al. Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. Metabolism. Jan 2009;58(1):109-119.
Zhang H, Wei J, Xue R, et al. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism. Feb 2010;59(2):285-292.
Liu L, Yu YL, Yang JS, et al. Berberine suppresses intestinal disaccharidases with beneficial metabolic effects in diabetic states, evidences from in vivo and in vitro study. Naunyn Schmiedebergs Arch Pharmacol. Apr 2010;381(4):371-381.
Han J, Lin H, Huang W. Modulating gut microbiota as an anti-diabetic mechanism of berberine. Med Sci Monit. Jul 2011;17(7):RA164-167.
Zhang Y, Li X, Zou D, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab. Jul 2008;93(7):2559-2565.
Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. May 2008;57(5):712-717.
Affuso F, Ruvolo A, Micillo F, Sacca L, Fazio S. Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study. Nutr Metab Cardiovasc Dis. Nov 2010;20(9):656-661.
Kong WJ, Wei J, Zuo ZY, et al. Combination of simvastatin with berberine improves the lipid-lowering efficacy. Metabolism. Aug 2008;57(8):1029-1037.
Wang JM, Yang Z, Xu MG, et al. Berberine-induced decline in circulating CD31+/CD42- microparticles is associated with improvement of endothelial function in humans. Eur J Pharmacol. Jul 1 2009;614(1-3):77-83.