Support for healthy blood sugar levels, insulin sensitivity and cardiovascular health
By David M. Brady, ND, DC, CCN, DACBN & Amy Berger, MS
THIS INFORMATION IS PROVIDED FOR THE USE OF PHYSICIANS AND OTHER LICENSED HEALTH CARE PRACTITIONERS ONLY. THIS INFORMATION IS INTENDED FOR PHYSICIANS AND OTHER LICENSED HEALTH CARE PROVIDERS TO USE AS A BASIS FOR DETERMINING WHETHER OR NOT TO RECOMMEND THESE PRODUCTS TO THEIR PATIENTS. THIS MEDICAL AND SCIENTIFIC INFORMATION IS NOT FOR USE BY CONSUMERS. THE DIETARY SUPPLEMENT PRODUCTS OFFERED BY DESIGNS FOR HEALTH ARE NOT INTENDED FOR USE BY CONSUMERS AS A MEANS TO CURE, TREAT, PREVENT, DIAGNOSE, OR MITIGATE ANY DISEASE OR OTHER MEDICAL CONDITION.
Berberine Synergy may be beneficial for the support of:
- Diabetes and pre-diabetes
- Insulin resistance/hyperinsulinemia
- Elevated triglycerides
- Non-alcoholic fatty liver
- PCOS linked to elevated insulin
Berberine SynergyTM combines 400mg of the plant alkaloid berberine (from Berberis aristata) along with 100 mg of alpha lipoic acid per capsule, in order to help support the management of blood sugar levels and insulin sensitivity. As downstream effects of these main actions, berberine may also help improve dyslipidemia, as well as other features of metabolic syndrome.
Insulin and Blood Glucose Management
The most prominent of berberine’s pharmacological properties are its bene cial effects on insulin and blood glucose management. Berberine exerts its effects independently of the mechanisms of metformin and other common hypoglycemic agents, so the compound may be used alone or in conjunction with conventional pharmaceutical drugs. In fact, berberine has been shown to be as effective as metformin in lowering fasting blood glucose and hemoglobin A1c (HbA1c), LDL-C, triglycerides, and fasting insulin.1 When added to the existing medication regimens of patients with poorly controlled diabetes, berberine signi cantly reduced fasting and postprandial blood glucose, insulin, HbA1c and HOMA-IR. These changes were observed after just ve weeks of berberine supplementation.1
In a separate study on newly diagnosed type-2 diabetics with dyslipidemia, berberine supplementation resulted in favorable changes to triglycerides, uric acid, total cholesterol, HOMA-IR, fasting insulin, LDL-C, HbA1c, fasting glucose, blood glucose and plasma insulin after a glucose loading test.2
Research supports berberine’s impressive effects on diabetes management and shows that it may be especially effective for diabetic patients with compromised liver function, for whom the potential adverse side-effects of conventional hypoglyce- mic drugs may not be an option.3 In study subjects with chronic hepatitis, berberine supplementation resulted in decreased enzyme markers for liver damage (ALT and AST), as well as decreased gamma-glutamyl transferase (GGT) in subjects without liver damage.3
There are multiple mechanisms behind berberine’s in uence on blood glucose control and insulin sensitivity. In diabetics using insulin, the addition of berberine resulted in increased fasting and postprandial C-peptide, which suggests that long- term use of berberine might improve insulin secretion in patients who fail to respond, or respond poorly, to oral hypoglyce- mic agents.11 In addition to increased insulin secretion, berberine has been shown to increase insulin receptor expression, indicating that it may improve glycemic control by supporting the endogenous production of insulin while also facilitating clearance of the hormone. Cultured human liver and muscle cells show increased insulin receptor protein expression when exposed to berberine.3 Moreover, contrary to thiazolidinedione drugs (TZDs), berberine “suppresses the differentiation of preadipocytes, and reduces the accumulation of lipid droplets.”3 This suggests berberine might be especially useful in cases of overweight or obese diabetics, where the potential for additional weight gain and edema associated with conventional pharmaceuticals would be undesirable.
Another biochemical mechanism behind berberine’s impressive effects is the inhibition of intestinal carbohydrate-digesting enzymes. Diabetic rats supplemented orally with berberine showed signi cant, dose-dependent decreases in disacchari- dase activity and sucrase-isomaltase complex mRNA expression in the intestines. Similar effects were observed in non- diabetic rats, suggesting that berberine may be helpful for pre-diabetic patients, as well as others presenting with indicators of carbohydrate intolerance. Notably, compared to healthy controls, the diabetic rats had up to a 7-fold increase in sucrase activity and a 2.5-fold increase in maltase activity in the small intestine, suggesting that an intervention targeting reduced activity of these enzymes may have impressive effects on postprandial blood glucose levels. Two-hour area under the curve (AUC) for blood glucose levels after sucrose and maltose loading were lower in non-diabetic, berberine treated rats than in untreated controls. Similar ndings for berberine’s in uence on carbohydrate-digesting enzymes are supported by observa- tions in cultured human cell lines.4
Beyond these roles in helping to regulate blood glucose and insulin, berberine may also support a healthy me- tabolism and lighten overall body burden by easing oxi- dative stress and restoring cellular redox ef ciency. With mitochondrial dysfunction being increasingly tied to a host of poor health outcomes, supporting mitochondrial exibility may be of particular importance in hyperinsu- linism and metabolic syndrome, with their various down- stream effects on multiple organs and tissue systems. A study employing cultured human macrophages exposed to lipopolysaccharide (LPS, a potent endotoxin) showed that berberine led to reduced superoxide radical levels, compared to LPS-treated controls without berberine. At 24-hours of incubation with berberine, superoxide levels in LPS-treated cells were even lower than controls un- treated with LPS.5
Blood Lipids and Liver Health
Berberine has been shown to exert favorable effects on blood lipids and non-alcoholic fatty liver. Unlike statin drugs, berberine does not affect the complex cholesterol biosynthesis pathway, and therefore does not present the same undesirable side-effects.
Berberine upregulates the expression of LDL receptor mRNA and increases liver expression of LDL receptors, allowing for more effective clearance of LDLs from the bloodstream.6,7 Diabetic, dyslipidemic rats supplemented with berberine showed favorable changes to total cholesterol, triglycerides, LDL-C, ApoB, and HDL-C. For some parameters, the effects were more powerful than those achieved with rosiglitazone and feno brate.8
In rats fed a fatty liver-inducing diet, supplemental berberine resulted in decreased total body weight, visceral adiposity, total cholesterol, LDL-C and triglycerides, while also reducing serum ALT and AST, which suggests a protective effect for liver function. These markers were reduced compared to fatty liver rats not supplemented with berberine, but more notably, some of these parameters were reduced to levels seen in a healthy control group fed a normal diet. Rats supplemented with berberine had lower liver weights and lower triglyceride content in the liver. Researchers concluded that berberine has direct effects upon the methylation status of genes involved in deposition of triglycerides in the liver.9
Berberine has also been demonstrated to reduce brosis in chemically induced liver damage.10,11 Because the liver is a key player in glycemic control, compounds that aid in blood sugar handling while simultaneously conferring signi cant protection to liver function may be powerful tools in the arsenal against metabolic syndrome.
Lipoic Acid: Antioxidant and Blood Sugar Support
Lipoic acid is best known as a lipid and water-soluble antioxidant, but it also powerfully in uences insulin secretion and sen- sitivity. The combination of lipoic acid and berberine has a strong potential to help patients improve their glycemic control. Like berberine, lipoic acid exerts effects upon the insulin receptor, but also aids in glucoregulation by facilitating recruit- ment of insulin-sensitive glucose transporters (GLUT-4 and GLUT-1) to muscle and adipose cell membranes.13,14 A study involving type-2 diabetics showed that oral lipoic acid resulted in insulin sensitivity and glucose disposal rates that were not signi cantly different from those of healthy, non-diabetic controls.15
Related to its antioxidant function, lipoic acid is a key cofactor for mitochondrial enzymes involved in cellular metabolism and energy (ATP) production, speci cally pyruvate dehydrogenase and a-ketoglutarate dehydrogenase. Lipoic acid is some- times called an “antioxidant of antioxidants,”16 as it can regenerate vitamins E and C, coenzyme Q10 and glutathione. In fact, lipoic acid has an even greater redox potential than glutathione.16,17 Mitochondrial oxidative stress may be both a cause and an effect of impaired carbohydrate tolerance, and lipoic acid may be bene cial for comprehensively addressing this issue.
Note: Patients taking this product should be monitored closely, as their medication may require adjustment to account for the ef cacy of berberine regarding blood glucose and insulin levels.
Berberine SynergyTM References
- Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism. 2008 May;57(5):712-7.
- Gu, Y, et al. Effect of traditional Chinese medicine berberine on type 2 diabetes based on comprehensive metabonomics. Talanta. 2010 May 15;81(3):766-72.
- Zhang, H, et al. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism. 2010 Feb;59(2):285-92.
- Liu, L, et al. Berberine suppresses intestinal disaccharidases with beneficial metabolic effects in diabetic states, evidences from in vivo and in vitro study. Naunyn Schmiedebergs Arch Pharmacol. 2010 Apr;381(4):371-81.
- Sarna LK, Wu N, Hwang SY, Siow YL, O K. Berberine inhibits NADPH oxidase mediated superoxide anion production in macrophages. Can J Physiol Pharmacol. 2010 Mar;88(3):369-78.
- Li H, Dong B, Park SW, Lee HS, Chen W, Liu J. Hepatocyte nuclear factor 1alpha plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine. J Biol Chem. 2009 Oct 16;284(42):28885-95.
- Abidi P, Zhou Y, Jiang JD, Liu J. Extracellular signal-regulated kinase-dependent stabilization of hepatic low-density lipoprotein receptor mRNA by herbal medicine berberine. Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2170-6.
- Zhou, JY, et al. Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic hyperlipidemic rats. Biol Pharm Bull. 2008 Jun;31(6):1169-76.
- Chang, Xin Xia, et al. Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by a high-fat diet in rats. Journal of Lipid Research. 51, 2504-2515.
- Sun X, Zhang X, Hu H, Lu Y, Chen J, Yasuda K, Wang H. Berberine inhibits hepatic stellate cell proliferation and prevents experimental liver fibrosis. Biol Pharm Bull. 2009 Sep;32(9):1533-7.
- Cheng, Z, et al. Foxo1 integrates insulin signaling with mitochondrial function in the liver. Nat Med. 2009 Nov;15(11):1307-11.
- Rochette L, Ghibu S, Richard C, Zeller M, Cottin Y, Vergely C. Direct and indirect antioxidant properties of a-lipoic acid and therapeutic potential. Mol Nutr Food Res. 2013 Jan;57(1):114-25.
- Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009 Oct;1790(10):1149-60.
- Moini H, Tirosh O, Park YC, Cho KJ, Packer L. R-alpha-lipoic acid action on cell redox status, the insulin receptor, and glucose uptake in 3T3-L1 adipocytes. Arch Biochem Biophys. 2002 Jan 15;397(2):384-91.
- Kamenova, P. Improvement of insulin sensitivity in patients with type 2 diabetes mellitus after oral administration of alpha-lipoic acid. Hormones (Athens). 2006 Oct- Dec;5(4):251-8.
- Goraca A, Huk-Kolega H, Piechota A, Kleniewska P, Ciejka E, Skibska B. Lipoic acid - biological activity and therapeutic potential. Pharmacol Rep. 2011;63(4):849-58.
- Packer L, Witt EH, Tritschler HJ. alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med. 1995 Aug;19(2):227-50.
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