The hypoglycemic effect of berberine was reported in 1988 when it was used to treat diarrhea in diabetic patients in China [8
]. Since then, berberine has often been used as an anti-hyperglycemic agent by many physicians in China. There are substantial numbers of clinical reports about the hypoglycemic action of berberine in Chinese literature. However, most of the previous studies were not well-controlled and experiments were not well-designed. Additionally, none of them used HbA1c
as a parameter due to poor research conditions. Thus, the anti-diabetic effect of berberine needs to be carefully evaluated.
In this pilot study, berberine significantly decreased HbA1c
levels in diabetic patients. The effect of decreasing HbA1c was comparable to that of metformin, a widely-used oral hypoglycemic agent [9
]. In monotherapy, berberine and metformin all improved glycemic parameters (HbA1c
, FBG and PBG). But their effects on lipid metabolism were different. Berberine decreased serum triglyceride and total cholesterol significantly. HDL-C and LDL-C levels of patients treated with barbering were also reduced but the decreases did not reach statistic significance. Whether berberine has a lowering effect on HDL-C needs further investigation. Compared with berberine, metformin had little effects on these lipid parameters.
In combination with other agents, berberine exhibited consistent activities in improvement of glycemic and lipid parameters in diabetic patients. Insulin sensitivity was enhanced by berberine as the HOMA-IR value was reduced by nearly 50%. This effect may be related to fat distribution by berberine because waist and waist/hip of the patients were decreased significantly in the absence of weight change. Interestingly, both fasting and postprandial C-peptides increased significantly in patients when berberine was used together with insulin, which suggests that long-term berberine treatment may improve insulin secretion of the patients with consequent failure of oral hypoglycemic agents. The effects of berberine on islet function need further studies.
The mechanism of berberine on glucose metabolism is still under investigation. We and others have demonstrated that berberine has an insulin sensitizing effect in vivo and in vitro [3
]. In diet-induced obese rats, berberine reduced insulin resistance, similar to metformin [13
]. In hepatocytes, adipocytes and myotubes, berberine increased glucose consumption and/or glucose uptake in the absence of insulin [3
]. Berberine enhancing glucose metabolism may be due to stimulation of glycolysis, which is related to inhibition of oxidation in mitochondria [6
]. Berberine may also act as an alpha-glucosidase inhibitor. It inhibited disaccharidases activities and decreased glucose transportation cross the intestinal epithelium [15
]. This may contribute to the adverse gastrointestinal effects of berberine in some patients. This side effect was often observed when berberine was used in combination with metformin or acarbose, which also have similar gastrointestinal side effects by themselves. Thus, when combined with these two agents, the dosage of berberine should be reduced to 0.3 g t.i.d. to avoid the severe flatulence or diarrhea.
Berberine is proposed to have potential as a therapeutic agent for lipid lowering. In this pilot study, berberine reduced serum cholesterol, triglycerides and LDL-C. This activity is similar to that reported elsewhere in vivo [17
]. However, further studies including outcome studies in humans are needed to confirm this activity and its benefit. The mechanism of berberine regulating lipid metabolism has been investigated by several groups. In hamsters with hyperlipidemia, berberine reduced serum cholesterol and LDL-C, and increased LDL receptor mRNA as well as protein in the liver [19
]. These effects were partly due to stabilization of LDL receptor mRNA mediated by the ERK signaling pathway [20
]. In addition to up-regulation of the LDL receptor, berberine was reported to inhibit lipid synthesis in human hepatocytes through activation of AMPK [21
In summary, that berberine is a potent oral hypoglycemic agent with modest effect on lipid metabolism. It is safe and the cost of treatment by berberine is very low. It may serve as a new drug candidate in the treatment of type 2 diabetes. However, this is a pilot study. The efficacy of berberine needs to be tested in a much larger population and characterized as a function of the known duration of the diabetes. Further studies are needed to evaluate the action of berberine on type 2 diabetes in other ethnic groups.