Alpha lipoic acid, sometimes called thioctic acid, is an endogenously synthesised coenzyme in human metabolism. Its primary role is as a cofactor in mitochondrial dehydrogenase complexes, and it is therefore pivotal in energy producing pathways. However, alpha lipoic acid has a more general function as an antioxidant. Alpha lipoic acid is unusual in that it acts as an antioxidant in both water and lipid soluble compartments and so can interact with the water soluble vitamin C and glutathione, as well as the lipid soluble vitamin E and ubiquinone antioxidants. This makes alpha lipoic acid highly effective at reducing oxidative stress in tissues. Alpha lipoic acid is synthesised primarily in the liver where cells produces two enantiomer, both an R- and S-isomer. However, only the R-isomer has biological activity, and S-isomer concentrations are not high in tissues. However, most supplements of alpha lipoic acid contain both isomers, although only the R-form will be biologically active.
Alpha lipoic acid can activate the insulin signalling pathway insulin receptor substrate-1 (IRS-1) protein and phosphatidylinositol 3-kinase which enhances glucose uptake. In addition alpha lipoic acid is a potent antioxidant in humans, oxidative stress being associated with inhibition of glucose uptake. Therefore alpha lipoic acid may be a useful glucose disposal agent. The ability of alpha lipoic acid to improve glucose disposal in patients with diabetes has been well reported. For example, in one study1, researchers administered oral alpha lipoic acid supplements at a dose of 600 mg twice per day for 4 weeks to subjects with type 2 diabetes. The treatment with alpha lipoic acid significantly improved the insulin sensitivity index and glucose disposal rates of the diabetic subjects and there was a trend for lowered levels of fasting blood glucose. The body weight of the patients did not change suggesting that the improvements in blood glucose disposal rate was not caused indirectly by a reduction in body weight but directly by cellular changes.
These results therefore confirm other studies that show beneficial effects for alpha lipoic acid as a glucose disposal agent. Studies suggest that alpha lipoic acid is effective in both lean and overweight diabetic subjects. Typically the improvement in insulin sensitivity seen with 600 mg to 1000 mg per day is around 15 to 20 %, in patients with type 2 diabetes. Alpha lipoic acid appears to mimic the effects of insulin by activation of the insulin signal pathway. A number of cell culture experiments have been performed and these show that alpha lipoic acid increases glucose uptake to cells through a mechanism that increases the availability of glucose transporters (GLUT1 and GLUT4) on the cell membrane. However, although a number of second messengers and second messenger system components have been shown to be activated by alpha lipoic acid, the mechanism by which it can mimic insulin is not know. Alpha lipoic acid also stimulates glucose oxidation and glycogen synthesis.
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