Berberine as effective as the drug metformin

Berberine for Diabetes Mellitus Type 2
By Ronald Steriti, ND, PhD

Abstract

This brief review focuses on several studies that show the plant alkaloid berberine can lower blood glucose as effectively as the drug metformin at similar doses (500 mg 3x/day). Berberine acts on glucose metabolism through several mechanisms, including (AMP-activated protein kinase) AMPK and incretins.

Berberine

Berberine is a plant alkaloid found in Hydrastis canadensis (goldenseal), Coptis chinensis (Coptis or goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric).

It has a long history of medicinal use in both Ayurvedic and Chinese medicine.1 Berberine has a wide range of effects that include antimicrobial (against bacterial diarrhea, intestinal parasites, fungal infections, Candida albicans, yeast, and possibly methicillinresistant Staphylococcus aureus); anti-inflammatory; and cardiovascular.2,3

Berberine for Diabetes Mellitus Type 2

Berberine has been shown to lower elevated blood glucose as effectively as metformin (500 mg 3x/day of each). Two studies on this topic were published in Metabolism.4 In study A, 36 adults with newly diagnosed type 2 diabetes mellitus were randomly assigned to treatment with berberine or metformin (500 mg 3x/day) in a 3-month trial. The hypoglycemic effect of berberine was similar to that of metformin. Significant changes were observed in the berberine group:

· Hemoglobin A1c decreased from 9.5% to 7.5%.
· Fasting blood glucose (FBG) decreased from 10.6 to 6.9 mmol/L (190.8 to 124.2 mg/dl).
· Postprandial blood glucose (PBG) decreased from 19.8 to 11.1 mmol/L (356.4 to 199.8 mg/dl).
· Plasma triglycerides from 1.13 to 0.89 mmol/L (100.5 to 79.2 mg/dl).

In study B, 48 adults with poorly controlled type 2 diabetes mellitus were supplemented with berberine in a 3-month trial:

· In the first 7 days of treatment, berberine led to a reduction in FBG from 9.6 to 7.8 mmol/L (172.8 to 140.4 mg/dl) and PBG from 14.8 to 11.7 mmol/ L (266.4 to 210.6 mg/dl).
· During the second week, FBG and PBG declined further, reached a nadir that was 2.1 mmol/L (7.5 mmol/L) and 3.3 mmol/L (10.5 mmol/L) (37.8; 135 and 59.4; 189 mg/ dl) below the baseline, respectively, and remained at this level thereafter.
· Hemoglobin A1c decreased from 8.1% to 7.3%.
· Fasting plasma insulin was reduced by 28.1%.
· The homeostasis model assessment of insulin resistance index was reduced by 44.7%.
· Total cholesterol and low-density lipoprotein cholesterol were decreased significantly.

During the trial, 20 (34.5%) patients experienced transient gastrointestinal adverse effects. Functional liver or kidney
damages were not observed in any patients.

Another study published in the Journal of Clinical EndocrinologyMetabolism showed that berberine benefits type 2 diabetes.5 One hundred sixteen patients with type 2 diabetes and dyslipidemia were randomly allocated to receive berberine (1.0 g daily) or placebo for 3 months. In the berberine group,

· fasting plasma glucose decreased from 7.0 to 5.6 mm/L (126 to 100.8 mg/dl),
· post-load plasma glucose decreased from 12.0 to 8.9 mm/L (216 to 160.2 mg/dl),
· HbA1c decreased from 7.5% to 6.6%,
· triglycerides decreased from 2.51 to 1.61 mm/L (220 to 141 mg/dl),
· total cholesterol decreased from 5.31 to 4.35 mm/L (205 to 168 mg/dl), and
· LDL cholesterol decreased from 3.23 to 2.55 mm/L (124.9 to 98.6 mg/dl),

The glucose disposal rate was increased after berberine treatment (P=0.037), although no significant change was found
between berberine and placebo groups (P=0.063). Mild to moderate constipation was observed in 5 participants in the
berberine group.

Mechanism of Action

Berberine has been found to act on glucose metabolism through several mechanisms:

· Mimicking insulin action6
· Improving insulin action by activating AMPK7,8,9,10
· Reducing insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression11,12
· Inducing glycolysis13
· Promoting GLP-1 secretion and modulating its release14,15
· Inhibition of DPP-416
· AMP-Activated Protein Kinase

The enzyme 5' adenosine monophosphate-activated protein kinase (AMPK) plays a role in cellular energy homeostasis.
AMPK is expressed in a number of tissues, including the liver, brain, and skeletal muscle. AMPK acts as a “metabolic master switch” that regulates several intracellular systems, including the cellular uptake of glucose, the beta-oxidation of fatty acids, and the biogenesis of glucose transporter 4 (GLUT4).17

The net effect of AMPK activation is stimulation of hepatic fatty acid oxidation and ketogenesis; inhibition of cholesterol
synthesis, lipogenesis, and triglyceride synthesis; inhibition of adipocyte lipolysis and lipogenesis; stimulation of skeletal
muscle fatty acid oxidation and muscle glucose uptake; and modulation of insulin secretion by pancreatic beta-cells.18

Incretins

Incretins are a group of gastrointestinal hormones that cause a short-term increase in the amount of insulin released from the beta cells of the islets of Langerhans after eating, which anticipates the postprandial increase in blood glucose. They also slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake. In addition, they inhibit glucagon release from the alpha cells of the islets of Langerhans. There are 2 main incretins: GLP-1 (glucagon-like peptide-1) and GIP (gastric inhibitory peptide). Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4).

Several approved drugs act on incretins. Exenatide (Byetta) is a synthetic version of exendin-4, a hormone found in the saliva of the Gila monster with biological properties similar to GLP-1. Liraglutide (Victoza) is a long-acting GLP-1 analog. Januvia (Sitagliptin) and Onglyza (Saxagliptin) are DPP-4 inhibitors.

Adverse effects

Transient gastrointestinal adverse effects with berberine were fairly common and may be related to its antimicrobial action. Berberine may be particularly useful in cases involving both type 2 diabetes and infection.

Berberine should be avoided in pregnancy.19

Conclusion

Berberine (at doses of 500 and 1,000 mg 3x/day) has been shown to have a significant beneficial effect on diabetes mellitus type 2, and may be as effective as metformin (500 mg 3x/day). Berberine acts through several mechanisms, including mimicking insulin; improving insulin action by activating AMPK; reducing insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression; inducing glycolysis; and on incretins by promoting GLP-1 secretion and modulating its release, and by inhibiting DPP-4.

About the Author
Ronald Steriti, ND, is a researcher for Dr. Jonathan V. Wright, director of the Tahoma Clinic and Meridian Valley Labs. Steriti is a graduate of the Southwest College of Naturopathic Medicine.

References

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2 Ibid.
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