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

This brief review focuses on several studies that show the plant alkaloid berberine can lower
blood glucose as ef ectively 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 (gold-
3.3 mmol/L (10.5 mmol/L) (37.8; 135 and 59.4; 189 mg/ enseal), Coptis chinensis (Coptis or goldenthread), Berberis aqui- dl) below the baseline, respectively, and remained at this folium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric). It has a long history of medicinal use in • Hemoglobin A1c decreased from 8.1% to 7.3%. • Fasting plasma insulin was reduced by 28.1%.
Berberine has a wide range of effects that include antimi- • The homeostasis model assessment of insulin resistance crobial (against bacterial diarrhea, intestinal parasites, fungal infections, Candida albicans, yeast, and possibly methicillin- • Total cholesterol and low-density lipoprotein cholesterol resistant Staphylococcus aureus); anti-inflammatory; and During the trial, 20 (34.5%) patients experienced tran- sient gastrointestinal adverse effects. Functional liver or kidney Berberine for Diabetes Mellitus Type 2
damages were not observed in any patients. Berberine has been shown to lower elevated blood glucose as Another study published in the Journal of Clinical Endo- effectively as metformin (500 mg 3x/day of each). Two studies crinology Metabolism showed that berberine benefits type on this topic were published in Metabolism.4 In study A, 36 2 diabetes.5 One hundred sixteen patients with type 2 adults with newly diagnosed type 2 diabetes mellitus were diabetes and dyslipidemia were randomly allocated to receive randomly assigned to treatment with berberine or metformin berberine (1.0 g daily) or placebo for 3 months. In the (500 mg 3x/day) in a 3-month trial. The hypoglycemic effect of berberine was similar to that of metformin. Significant changes • fasting plasma glucose decreased from 7.0 to 5.6 mm/L • Hemoglobin A1c decreased from 9.5% to 7.5%.
• post-load plasma glucose decreased from 12.0 to 8.9 • Fasting blood glucose (FBG) decreased from 10.6 to 6.9 • Postprandial blood glucose (PBG) decreased from 19.8 to • triglycerides decreased from 2.51 to 1.61 mm/L (220 to • Plasma triglycerides from 1.13 to 0.89 mmol/L (100.5 to • total cholesterol decreased from 5.31 to 4.35 mm/L (205 In study B, 48 adults with poorly controlled type 2 diabetes • LDL cholesterol decreased from 3.23 to 2.55 mm/L mellitus were supplemented with berberine in a 3-month trial: • In the first 7 days of treatment, berberine led to a reduction The glucose disposal rate was increased after berberine treat- in FBG from 9.6 to 7.8 mmol/L (172.8 to 140.4 mg/dl) and ment (P=0.037), although no significant change was found PBG from 14.8 to 11.7 mmol/ L (266.4 to 210.6 mg/dl). between berberine and placebo groups (P=0.063). Mild to • During the second week, FBG and PBG declined further, moderate constipation was observed in 5 participants in the reached a nadir that was 2.1 mmol/L (7.5 mmol/L) and 2010 Natural Medicine Journal 2(10), October 2010 | Page 5
Mechanism of Action
acts through several mechanisms, including mimicking insulin; Berberine has been found to act on glucose metabolism through improving insulin action by activating AMPK; reducing insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression; inducing glycolysis; and on incre- • Improving insulin action by activating AMPK7,8,9,10 tins by promoting GLP-1 secretion and modulating its release, • Reducing insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression11,12 About the Author
• Promoting GLP-1 secretion and modulating its release14,15 Ronald Steriti, ND, is a researcher for Dr. Jonathan V. Wright, director of the Tahoma Clinic and Meridian Valley Labs. Steriti is a AMP-Activated Protein Kinase
graduate of the Southwest College of Naturo- The enzyme 5' adenosine monophosphate-activated protein kinase (AMPK) plays a role in cellular energy homeostasis. References
AMPK is expressed in a number of tissues, including the liver, brain, and skeletal muscle.
Berberine. Altern Med Rev. Apr 2000;5(2):175-177.
AMPK acts as a “metabolic master switch” that regulates 2 several intracellular systems, including the cellular uptake of Yu HH, Kim KJ, Cha JD, et al. Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylo- glucose, the beta-oxidation of fatty acids, and the biogenesis of coccus aureus. J Med Food. Winter 2005;8(4):454-461.
Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes The net effect of AMPK activation is stimulation of hepatic mellitus. Metabolism. May 2008;57(5):712-717.
fatty acid oxidation and ketogenesis; inhibition of cholesterol Zhang Y, Li X, Zou D, et al. Treatment of type 2 diabetes and dyslipid-emia with the natural plant alkaloid berberine. J Clin Endocrinol Metab. Jul synthesis, lipogenesis, and triglyceride synthesis; inhibition of adipocyte lipolysis and lipogenesis; stimulation of skeletal 6 Chen C, Zhang Y, Huang C. Berberine inhibits PTP1B activity and mimics muscle fatty acid oxidation and muscle glucose uptake; and insulin action. Biochem Biophys Res Commun. Jul 2 2010;397(3):543-547.
modulation of insulin secretion by pancreatic beta-cells.18 Turner N, Li JY, Gosby A, et al. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a Incretins
mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes. May 2008;57(5):1414-1418.
Incretins are a group of gastrointestinal hormones that cause a Lee YS, Kim WS, Kim KH, et al. Berberine, a natural plant product, activates short-term increase in the amount of insulin released from the AMP-activated protein kinase with beneficial metabolic effects in diabetic and beta cells of the islets of Langerhans after eating, which antici- insulin-resistant states. Diabetes. Aug 2006;55(8):2256-2264.
pates the postprandial increase in blood glucose. They also slow Ma X, Egawa T, Kimura H, et al. Berberine-induced activation of 5’-adenosine monophosphate-activated protein kinase and glucose transport in rat skeletal the rate of absorption of nutrients into the blood stream by muscles. Metabolism. Apr 26 2010.
reducing gastric emptying and may directly reduce food intake. 10 Hwang JT, Kwon DY, Yoon SH. AMP-activated protein kinase: a potential target In addition, they inhibit glucagon release from the alpha cells for the diseases prevention by natural occurring polyphenols. N Biotechnol. Oct of the islets of Langerhans. There are 2 main incretins: GLP-1 (glucagon-like peptide-1) and GIP (gastric inhibitory peptide). 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 Both GLP-1 and GIP are rapidly inactivated by the enzyme 12 Kong WJ, Zhang H, Song DQ, et al. Berberine reduces insulin resistance Several approved drugs act on incretins. Exenatide (Byetta) is through protein kinase C-dependent up-regulation of insulin receptor expres-sion. Metabolism. Jan 2009;58(1):109-119.
a synthetic version of exendin-4, a hormone found in the saliva 13 Yin J, Gao Z, Liu D, Liu Z, Ye J. Berberine improves glucose metabo- of the Gila monster with biological properties similar to GLP-1. lism through induction of glycolysis. Am J Physiol Endocrinol Metab. Jan Liraglutide (Victoza) is a long-acting GLP-1 analog. Januvia (Sitagliptin) and Onglyza (Saxagliptin) are DPP-4 inhibitors.
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 Adverse effects
Transient gastrointestinal adverse effects with berberine were 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. fairly common and may be related to its antimicrobial action. Berberine may be particularly useful in cases involving both 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.
Berberine should be avoided in pregnancy.19 17 Winder WW, Hardie DG. AMP-activated protein kinase, a metabolic master Conclusion
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 AMP- Berberine (at doses of 500 and 1,000 mg 3x/day) has been shown activated protein kinase as a novel therapeutic approach for the treatment of to have a significant beneficial effect on diabetes mellitus type 2, metabolic disorders. Diabetes Metab. Dec 2007;33(6):395-402.
and may be as effective as metformin (500 mg 3x/day). Berberine 19 Berberine. Altern Med Rev. Apr 2000;5(2):175-177.
2010 Natural Medicine Journal 2(10), October 2010 | Page 6

Source: http://www.naturalmedicinejournal.net/pdf/NMJ_OCT10_LRberb.pdf


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Case 1:09-cv-01761-AJB Document 27 Filed 05/17/10 Page 1 of 58 IN THE UNITED STATES DISTRICT COURT FOR THE NORTHERN DISTRICT OF GEORGIA ATLANTA DIVISION GRACIE MARIE JAMIAH, Plaintiff, CIVIL ACTION FILE NO. 1:09-CV-01761-AJB MICHAEL J. ASTRUE, Commissioner of Social Security Administration , Defendant. ORDER 1 AND MEMORANDUM OPINION Plaintiff, Gracie Ma

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