~ Alpha-Lipoic Acid Completely Prevents Atherosclerosis In Diabetic Mice

An article published in the August, 2006 issue of the American Diabetes Association journal Diabetes reported the findings of Xianwen Yi and Nobuyo Maeda of the University of North Carolina at Chapel Hill that giving alpha-lipoic acid to mice in whom diabetes was induced prevented the increase in cholesterol, atherosclerotic lesions and health deterioration that the disease would otherwise cause. Alpha-lipoic acid is a potent antioxidant nutrient that has been used to treat diabetic neuropathy, however, its effects in diabetic cardiovascular disease have not been completely evaluated.

Drs Yi and Maeda, who are with UNC’s department of pathology and laboratory medicine, induced diabetes in a group of three-month-old apolipoprotein E-deficient mice by administering streptozotocin (STZ), while a control group was injected with a buffering solution. After four weeks on a regular diet, diabetic and nondiabetic mice were given a high fat diet enhanced with alpha-lipoic acid or the same diet without alpha-lipoic acid. Body weight, plasma glucose and cholesterol levels were determined at the beginning of the study and every four weeks thereafter up to twenty weeks. Red blood cell glutathione levels and oxidative stress markers were measured at the end of the study, at which time the animals were examined for the development of atherosclerotic plaque and for the treatment’s effect on pancreatic beta cells.

After twenty weeks, both diabetic and nondiabetic animals supplemented with alpha-lipoic acid had lower markers of oxidative stress and higher levels of red blood cell glutathione compared to mice that did not receive the compound. While many of the diabetic mice who did not receive alpha-lipoic acid began to show signs of lethargy and illness three months of the induction of the disease, all of the diabetic mice who received alpha-lipoic acid appeared healthy throughout the study period. “Remarkably,” the authors write, “alpha-lipoic acid completely prevented the increase in plasma total cholesterol, atherosclerotic lesions, and the general deterioration of health caused by diabetes.”

While the initial elevation in glucose levels that occurred after diabetes was induced gradually decreased in both mice who received and did not receive alpha-lipoic acid, glucose levels at 20 weeks were lower in the supplemented mice. The researchers attribute this to partial protection or regeneration of the beta cells in the pancreas by alpha-lipoic acid, due to the finding that mice who received the compound had a greater number of insulin-producing cells.

“In summary, our study demonstrates that dietary supplementation of alpha-lipoic acid for 20 weeks completely protects apoplipoprotein E-negative mice from enhancement of aortic atherosclerosis caused by STZ-induced diabetes,” the authors conclude. “Our results suggest that dietary alpha-lipoic acid is a promising agent for reducing cardiovascular complications of diabetes.”

Related Health Concern: Diabetes

A new approach to diabetes recognition and treatment is needed because the conventional wisdom has failed us. America is in the midst of a diabetes epidemic. Over the past 20 years, the number of adults diagnosed with diabetes has more than doubled, and children are being diagnosed with diabetes in alarming numbers. Diabetes has rapidly emerged as a leading culprit in the epidemic of heart disease that is sweeping the country, and it is a leading cause of amputation and blindness among adults.

As a powerful antioxidant, lipoic acid positively affects important aspects of diabetes, including blood sugar control and the development of long-term complications such as disease of the heart, kidneys, and small blood vessels (Jacob S et al 1995, 1999; Kawabata T et al 1994; Melhem MF et al 2002; Nagamatsu M et al 1995; Song KH et al 2005; Suzuki YJ et al 1992).

Lipoic acid plays a role in preventing diabetes by reducing fat accumulation. In animal studies, lipoic acid reduced body weight, protected pancreatic beta cells from destruction, and reduced triglyceride accumulation in skeletal muscle and pancreatic islets (Doggrell SA 2004; Song KH et al 2005).

Lipoic acid has been approved for the prevention and treatment of diabetic neuropathy in Germany for nearly 30 years. Intravenous and oral lipoic acid reduces symptoms of diabetic peripheral neuropathy ( Ametov AS et al 2003). Animal studies have suggested that lipoic acid is more effective when taken with gamma-linolenic acid (GLA) (Cameron NE et al 1998; Hounsom L et al 1998).


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