The Vital and Protective Role of Alpha Lipoic Acid in Blood Sugar Metabolism and Insulin Sensitivity Elevated blood sugar, elevated blood lipids, insulin resistance**, and the inflammation and oxidative stress*** associated with the disease process of Metabolic Syndrome (MetS), and type 2 diabetes, are the principle features that characterize and define the pathogenesis of these degenerative, and related disorders. Additionally, in type 2 diabetes there is often a diminshed capacity for insulin production by the pancreas that results from the toxic effects derived from elevated blood glucose, and lipids, on the insulin producing beta-cells of the pancreas.(4,5)

An example of research that demonstrates the effectiveness of ALA in type 2 diabetes, is a 2009 study of 57 type 2 diabetic patients--split into 2 groups, that were supplemented with 300 mg alpha lipoic acid per day or a placebo for a period of 8 weeks. The subjects were evaluated for baseline levels of fasting blood glucose (FBG), 2-hour post-prandial (after eating) blood glucose (PPG), serum insulin level, and the activity of the antioxidant enzyme, glutathione peroxidase (GPx). Elevated levels of GPx activity is an indicator of oxidative stress, and is associated with cardiovascular disease, and type 2 diabetes.(5) However, a decrease in GPx activity may also reflect a depletion stage of the antioxidant enzyme as it is exhausted by chronic oxidative stress, an insufficiency selenium, or glutathione as well. Selenium is an essential cofactor of GPx, and glutathione is an essential factor in GPx activity (GPx is commonly referred to as a selenoprotein enzyme, or selenoenzyme).

At the end of the 8 week study, there was a significant decrease in FBG, PPG and GPx levels in the group supplemented with ALA. The hallmark insulin resistance that characterizes the metabolic derangement of MetS, and type 2 diabetes, was reduced as well.(6)

In similar studies using rats, ALA has demonstrated to have antihypertensive benefits. Hypertension is a common clinical symptom associated with MetS & type 2 diabetes. The lowering of blood pressure by ALA is apparently mediated by it's function as an antioxidant. In an experimental animal model of hypertension associated with insulin resistance, a diet supplemented with ALA prevented elevations of blood pressure, insulin resistance, and the generation of oxygen radicals(7) (superoxide anion). ****

Positive correlations between the production of the oxygen radical, superoxide anion, and elevated blood pressure, and insulin resistance, illustrates the role of oxidative stress in MetS, and type 2 diabetes. Moreover, the Superoxide anion readily reacts with nitric oxide***** to generate an even more potent free radical-peroxynitrite (Please read my article: "Alpha lipoic acid Protects Brain Cells–Antioxidant Mechanisms For Alzheimer’s Prevention" for a detailed overview of ALA and it's role in preventing toxic peroxynitrite activity). Peroxynitrite is "a potent inducer of cell death"(8), and it is implicitly linked to cardiovascular, and neurological disease. Unregulated in their generation, the cascade of Superoxide anion/peroxynitrite induced oxidative stress, is central to the pathology associated with MetS and type 2 diabetes.

To summarize, ALA supplementation confers vital protection against developing type 2 diabetes, MetS, and the associated of insulin resistance, hypertension, and cardiovascular disease. ALA, and it' reduced form, DHLA are essential factors in glutathione synthesis and GPx activity. GPX is a vital component of the body's endogenous antioxidant enzyme system******, and said antioxidant enzymes, are a critical, and preventive mechanism in the cascade of radicals that are potent destructive agents of cellular damage, and cell death.

A premier product developed for supporting glucose metabolism, insulin sensitivity, and a clinically relevant dose of Alpha-Lipoic Acid, is Metabolic Synergy by Designs for Health. Metabolic Synergy is a foundational supplement formula for any individual diagnosed with MetS, or type 2 diabetes.

* Metabolic syndrome (insulin resistance syndrome), has been recognized as a prediabetic constellation of symptoms that increases risk for type 2 diabetes, and is an independent risk factor for cardiovascular disease.

** Insulin resistance describes the cellular resistance to insulin signaling in the process of glucose uptake into the cell. Chronic elevation of insulin, in response to excessive, and repeated elevations in blood glucose, eventually wears down cellular insulin sensitivity.

*** Oxidative Stress: Oxidative stress is a physiological condition whereby there is an imbalance between protective antioxidants and oxidative free radicals and other oxidants. The “oxidative balance” between antioxidants and the free radicals and oxidants that they quench, is a key element in optimizing health and buffering against the aging process and some of the degenerative diseases associated with it.

**** Superoxide anion...a byproduct of mitochondrial energy production. In excess, the superoxide anion is a potentially reactive molecule due to an unpaired outer oxygen electron

***** Nitric oxide (NO) is is a gas naturally found in the body. Nitric oxide is produced in the vasculature, and in the central, and peripheral nervous system, where it functions as a vasodilator, and a neurotransmitter respectively. However, NO is highly reactive, and abnormal production of NO can upregulate the production of the peroxynitrite radical, and thus contribute mightily to oxidative stress, and the free radical damage associated with it.

****** Antioxidant enzyme system...Glutathione peroxidase (GPx), Superoxide dismutase (SOD), and Catalase (CAT), are a family of antioxidant enzymes that remove reactive oxygen species (ROS), e.g., superoxide anion, and prevent more toxic radicals from being formed--e.g., peroxynitrite & hydroxyl radicals. GPx activity is dependent on the availability of glutathione. References

1. A current update on the use of alpha lipoic acid in the management of type 2 diabetes mellitus. Endocr Metab Immune Disord Drug Targets. 2009 Dec;9(4):392-8. Poh ZX, Goh KP.

2. Use of Antioxidant Nutrients in the Prevention and Treatment of Type 2 Diabetes Rodney C. Ruhe, PhD and Roger B. McDonald, PhD J Am Coll Nutr October 2001 vol. 20 no. suppl 5 363S-369S

3. β-Cell Glucose Toxicity, Lipotoxicity, and Chronic Oxidative Stress in Type 2 Diabetes R. Paul Robertson, Jamie Harmon, Phuong Oanh T. Tran and Vincent Poitout Diabetes February 2004 vol. 53 no. suppl 1 S119-S124

4. Lipid peroxidation and antioxidant enzyme activities in erythrocytes of type 2 diabetic patients. Likidlilid A, Patchanans N, Peerapatdit T, Sriratanasathavorn C. J Med Assoc Thai. 2010 Jun;93(6):682-93.

5. Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Robertson RP, Harmon J, Tran PO, Poitout V. Diabetes. 2004 Feb;53 Suppl 1:S119-24.

6. Ansar H, Mazloom Z, Kazemi F, Hejazi N. Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients. Saudi Med J. 2011 Jun;32(6):584-8.

7.Prevention of hypertension, insulin resistance, and oxidative stress by alpha-lipoic acid. El Midaoui A, de Champlain J. Hypertension. 2002 Feb;39(2):303-7.

8. Peroxynitrite: biochemistry, pathophysiology and development of therapeutics Csaba Szabó, Harry Ischiropoulos & Rafael Radi Nature Reviews Drug Discovery 6, 662-680 (August 2007)

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