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 is a plant alkaloid found in Hydrastis canadensis
(Coptis or goldenthread), Berberis aquifolium
(Oregon grape), Berberis vulgaris
(barberry), and Berberis
(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
); anti-inflammatory; and
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
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
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
• 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.
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 Endocrinology
showed that berberine benefits type
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
• 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
• 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
=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
Mechanism of Action
Berberine has been found to act on glucose metabolism through
•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 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.
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
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.
1 Berberine. Altern Med Rev. Apr 2000;5(2):175-177.
3 Yu HH, Kim KJ, Cha JD, et al. Antimicrobial activity of berberine alone and in
combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus
aureus. J Med Food. Winter 2005;8(4):454-461.
4 Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes
mellitus. Metabolism. May 2008;57(5):712-717.
5 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
6 Chen C, Zhang Y, Huang C. Berberine inhibits PTP1B activity and mimics
insulin action. Biochem Biophys Res Commun. Jul 2 2010;397(3):543-547.
7 Turner N, Li JY, Gosby A, et al. Berberine and its more biologically available
derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a
mechanism for the action of berberine to activate AMP-activated protein kinase
and improve insulin action. Diabetes. May 2008;57(5):1414-1418.
8 Lee YS, Kim WS, Kim KH, et al. Berberine, a natural plant product, activates
AMP-activated protein kinase with beneficial metabolic effects in diabetic and
insulin-resistant states. Diabetes. Aug 2006;55(8):2256-2264.
9 Ma X, Egawa T, Kimura H, et al. Berberine-induced activation of 5’-adenosine
monophosphate-activated protein kinase and glucose transport in rat skeletal
muscles. Metabolism. Apr 26 2010.
10 Hwang JT, Kwon DY, Yoon SH. AMP-activated protein kinase: a potential target
for the diseases prevention by natural occurring polyphenols. N Biotechnol. Oct
11 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
12 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.
13 Yin J, Gao Z, Liu D, Liu Z, Ye J. Berberine improves glucose metabolism
through induction of glycolysis. Am J Physiol Endocrinol Metab. Jan
14 Lu SS, Yu YL, Zhu HJ, et al. Berberine promotes glucagon-like peptide-1
(7-36) amide secretion in streptozotocin-induced diabetic rats. J Endocrinol. Feb
15 Yu Y, Liu L, Wang X, Liu X, Xie L, Wang G. Modulation of glucagon-like
peptide-1 release by berberine: in vivo and in vitro studies. Biochem Pharmacol.
Apr 1 2009;79(7):1000-1006.
16 Al-masri IM, Mohammad MK, Tahaa MO. Inhibition of dipeptidyl peptidase
IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of
berberine. J Enzyme Inhib Med Chem. Oct 2009;24(5):1061-1066.
17 Winder WW, Hardie DG. AMP-activated protein kinase, a metabolic master
switch: possible roles in type 2 diabetes. Am J Physiol. Jul 1999;277(1 Pt 1):E1-10.
18 Viollet B, Mounier R, Leclerc J, Yazigi A, Foretz M, Andreelli F. Targeting AMPactivated
protein kinase as a novel therapeutic approach for the treatment of
metabolic disorders. Diabetes Metab. Dec 2007;33(6):395-402.
19 Berberine. Altern Med Rev. Apr 2000;5(2):175-177.