Gastrointestinal

What Are the Potential Benefits of Berberine for Diabetes?

berberine for diabetes

For patients, being diagnosed with type 2 diabetes means far more than dealing with a single medical condition. Type 2 diabetes patients are challenged to contend with a broad spectrum of health concerns, ranging from blood sugar maintenance to weight management to diabetic neuropathy. There are individual treatment methods that can help patients address each aspect of the condition, but in recent years, there have been calls for the development of broad-spectrum solutions that simultaneously address multiple components of the condition, without subjecting patients to unwanted side effects.

One of the most promising all-natural treatment options that have risen to prominence in the literature is berberine, a plant extract that has long been used in traditional Chinese medicine. Following decades of research, researchers have developed a strong understanding of how this natural alkaloid works for patients with type 2 diabetes. The success of the in vitro research has driven animal studies suggesting possible ways in which berberine may have positive clinical effects on a wide range of type 2 diabetes symptoms. In the last few years, the first human studies have gotten underway, and although the clinical research is still in its infancy, it has the potential to clarify the specific benefits of berberine for diabetes patients.

The Cellular Mechanisms Underpinning the Effectiveness of Berberine

As an all-natural therapeutic, berberine stands out because scientists have a solid understanding of the specific cellular pathways through which it works to produce particular benefits for patients with type 2 diabetes. Specifically, berberine targets AMP-activated kinase (AMPK), an effector protein with a role in a wide range of energy production and utilization pathways. For instance, according to a 2006 study, berberine strongly promotes the phosphorylation of AMPK, which directly increases the AMP-to-ATP ratio in the cell and thereby stimulates glucose uptake. In this way, it can have a direct anti-hyperglycemic effect, which is highly relevant for type 2 diabetes patients.

It is also important to note that there are studies suggesting that berberine works through non-AMPK-related pathways. This is especially intriguing for patients and practitioners looking for a more comprehensive type 2 diabetes treatment option, since it could potentially enhance the AMPK-related effects of berberine as a therapeutic. For instance, in 2010, researchers at the Chinese Academy of Medical Sciences found that berberine increases the expression of insulin receptors, indicating the potential for a prominent role in reducing insulin resistance in type 2 diabetes patients. There is also research to suggest that berberine may help lower LDL cholesterol by increasing the degradation of PCSK9, a protein that downregulates the low-density lipoprotein (LDL) receptor. Because researchers are continuing to find associations between berberine and a variety of cellular pathways, there is ongoing interest within the research community to elucidate additional mechanisms through which this multifunctional compound may be able to help patients with type 2 diabetes.

Intriguing Studies on Berberine in Animal Models of Diabetes

In light of the promising mechanistic research on the role that berberine may play in the management of type 2 diabetes, researchers have conducted a numerous relevant studies in animal models over the last few decades. For instance, in one rat model of diabetes, administration of berberine at 100 mg/kg or 200 mg/kg led to lower fasting glucose levels as well as an increase in HDL (good) cholesterol levels and an accompanying decline in total cholesterol, triglycerides, and LDL (bad) cholesterol levels. Even more promising, the researchers found that supplementation with berberine effectively reduced damage in the pancreatic tissues of the diabetes rat models, which suggests that berberine may actually slow the progression of the disease itself.

Studies in animal models indicate that berberine may also aid in the prevention and treatment of some of the most common complications of type 2 diabetes, including the following:

Obesity

In a 2010 study, researchers at South Dakota State University found that berberine may be effective for reducing the risk of obesity in type 2 diabetes patients. In their mouse models, berberine supplementation directly inhibited adipogenesis–that is, the generation of fat cells.

Diabetic Neuropathy

Nerve damage is one of the most debilitating complications of type 2 diabetes. Through multiple inflammation-related pathways, berberine may help reduce the risk of diabetic neuropathy. In a 2013 study, researchers at Kyungpook National University and Keimyung School of Medicine in South Korea found that it was also as effective a some of the traditional pharmacological agents for reducing pain in patients with diabetic neuropathy.

Kidney Damage

A 2010 study published in the Archives of Biochemistry and Biophysics showed that berberine had protective effects on the kidneys of rat models of diabetes, slowing the progression of kidney damage that can eventually lead to renal failure in patients with type 2 diabetes.

Cognitive Decline

Memory impairment and other signs of cognitive decline are common among type 2 diabetes patients. Through a combination of protein expression studies, brain imaging, and behavioral tests on rat models, researchers at Huazhong University of Science and Technology in China found that administration of berberine could reduce diabetes-associated cognitive decline.

Studies in Humans: Preliminary Research and Opportunities for Future Studies

So far, most of the studies on berberine have been conducted in vitro and on animal models, but the few clinical studies that have been conducted have produced promising results. For instance, in a pilot study in 2008, researchers treated 36 newly-diagnosed type 2 diabetes patients with either berberine or metformin. In the berberine group, they observed statistically significant decreases in hemoglobin A1c levels, fasting blood glucose, postprandial blood glucose, and plasma triglycerides, starting only one week after the trial began. This hypoglycemic effect was comparable to that of metformin. Then, in a follow-up trial, they recruited 48 adults with poorly-controlled type 2 diabetes, and they found that there was a statistically significant decline in hemoglobin A1c (an average decline of 8.1% to 7.3% over the course of the three-month trial), as well as a statistically significant increase in their insulin resistance index (an average rise of 28.1% to 44.7%). The researchers concluded that this pilot study suggested that berberine, when taken as an oral supplement, could have powerful effects on lipid metabolism, warranting larger scale clinical studies on type 2 diabetes patients in the future.

Other early studies on berberine were conducted over the next few years. According to the authors of a meta-analytic review of 14 human studies—in which berberine supplementation was compared to lifestyle modification, placebo, and/or alternative oral therapeutics—the compound has considerable promise for the treatment of type 2 diabetes. In the clinic, berberine has consistently been shown to improve glycemic control, and some studies have also highlighted antidyslipidemic effects, although these impacts were less prominent. Importantly, the authors warn that these results should be considered with skepticism, given the relatively low methodological quality of the studies in question. For example, when combined, the data from the meta-analysis includes over a thousand patients, but most of the individual studies had relatively small sample populations. These concerns indicate that there is ample room for researchers to rigorously explore the measurable clinical impacts of berberine supplementation for type 2 diabetes patients in the future.

Nevertheless, patient and practitioners today are already taking advantage of the significant body of existing research evidence. Despite the lack of large-scale clinical trials on berberine for type 2 diabetes patients, the mechanistic evidence for the compound’s efficacy is considerable, and the success of animal studies strongly suggests that the biochemical studies are translatable to the clinic.  For patients and practitioners looking for a comprehensive solution for type 2 diabetes, it may be worth considering berberine as a therapeutic option.

Foundational Medicine Review is committed to helping researchers, practitioners, and patients understand the most relevant research related to the prevention and treatment of a wide range of prominent health conditions, including diabetes. Join our mailing list today to stay up-to-date with the most compelling research in the biomedical field.

Works Cited

Affuso F, Mercurio V, Fazio V, Fazio S. 2010. Cardiovascular and metabolic effects of berberine. World Journal of Cardiology. 2(4):71-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999047/

Cameron J, Ranheim T, Kulseth MA, Leren  TP, Berge KE. 2008. Berberine decreases PCSK9 expression in HepG2 cells. Atherosclerosis. 201(2):266-73. https://www.ncbi.nlm.nih.gov/pubmed/18355829/

Chang W, Chen L, Hatch GM. 2015. Berberine as a therapy for type 2 diabetes and its complications: From mechanism of action to clinical studies. Biochemistry and Cell Biology. 93(5):479-86. https://www.ncbi.nlm.nih.gov/pubmed/25607236

Chen Q, Mo R, Wu N, Zhou X, Shi C, et al. 2017. Berberine ameliorates diabetes-associated cognitive decline through modulation of aberrant inflammation response and insulin signaling pathway in DM rats. Frontiers in Pharmacology. 8:334. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460072/

Cheng Z, Pang T, Gu M, Gao AH, Xie CM, et al. 2006. Berberine-stimulated glucose uptake in L6 myotubes involves both AMPK and p38 MAPK. Biochimica et Biophysica Acta. 1760(11):1682-9. https://www.ncbi.nlm.nih.gov/pubmed/17049164

Dong H, Wang N, Zhao L, Lu F. 2012. Berberine in the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis. Evidence-Based Complementary and Alternative Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478874/

Hu Y, Davies GE. 2010. Berberine inhibits adipogenesis in high-fat diet-induced obesity mice. Fitoterapia. 81(5):358-66. https://www.sciencedirect.com/science/article/pii/S0367326X0900255X

Kim Si, Kim HJ. 2013. Berberine ameliorates cold and mechanical allodynia in a rat model of diabetic neuropathy. Journal of Medicinal Food. 16(6):511-517. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684108/

Lan T, Shen X, Liu P, Liu W, Xu S, et al. 2010. Berberine ameliorates renal injury in diabetic C57BL/6 mice: Involvement of suppression of SphK-S1P signaling pathway. Archives of Biochemistry and Biophysics. 502(2):112-20. https://www.ncbi.nlm.nih.gov/pubmed/20646989

Pang B, Zhao LH, Zhou Q, Zhao TY, Wang H, et al. 2015. Application of berberine on treating type 2 diabetes mellitus. International Journal of Endocrinology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377488/

Tang LQ, Wei W, Chen LM, Liu S. 2006. Effects of berberine on diabetes induced by alloxan and a high-fat/high-cholesterol diet in rats. Journal of Ethnopharmacology. 108(1):108-15. https://www.ncbi.nlm.nih.gov/pubmed/16759828

Wang H, Zhu C, Ying Y, Luo L, Huang D, Luo, Z. 2018. Metformin and berberine, two versatile drugs in treatment of common metabolic diseases. Oncotarget. 9(11):10135-46. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839379/

Wang Z, Wang J, Chan P. 2013. Treating type 2 diabetes mellitus with traditional Chinese and Indian medicinal herbs. Evidence-Based Complementary and Alternative Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662109/

Yin J, Xing H, Ye J. 2008. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 57(5):712-7. https://www.ncbi.nlm.nih.gov/pubmed/18442638

Zan Y, Kuai CX, Qiu ZC, Huang F. 2017. Berberine ameliorates diabetic neuropathy: TRPV1 modulation by PKC pathway. American Journal of Chinese Medicine. 45(8):1709-23. https://www.ncbi.nlm.nih.gov/pubmed/29121795

Zhang H, Wei J, Wu JD, Zhao W, Wang ZZ, et al. 2010. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism. 59(2):285-92. https://www.ncbi.nlm.nih.gov/pubmed/19800084

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