Alpha-lipoic Acid and diabetic neuropathy

Abstract

Diabetic neuropathy presents a major public health problem. It is defined by the symptoms and signs of peripheral nerve dysfunction in diabetic patients, in whom other causes of neuropathy have been excluded. Pathogenetic mechanisms that have been implicated in diabetic neuropathy are: a) increased flux through the polyol pathway, leading to accumulation of sorbitol, a reduction in myo-inositol, and an associated reduced Na+-K+-ATPase activity, and b) endoneurial microvascular damage and hypoxia due to nitric oxide inactivation by increased oxygen free radical activity. Alpha-lipoic acid seems to delay or reverse peripheral diabetic neuropathy through its multiple antioxidant properties. Treatment with alpha-lipoic acid increases reduced glutathione, an important endogenous antioxidant. In clinical trials, 600 mg alpha-lipoic acid has been shown to improve neuropathic deficits. This review focuses on the relationship of alpha-lipoic acid and auto-oxidative glycosylation. It discusses the impact of alpha-lipoic acid on hyperglycemia-induced oxidative stress, and examines the role of alpha-lipoic acid in preventing glycation process and nerve hypoxia.

Figure 1

Increased oxidative stress in diabetes appears to be mainly due to hyperglycemia, which leads to AGE formation and polyol pathway activation, resulting in subsequent formation of reactive oxygen species. AGE: advanced glycation end product.

Figure 2. The polyol pathway

The polyol pathway converts glucose to fructose via production of sorbitol. AR: aldose reductase. SDH: sorbitol dehydrogenase. AR inhibitors: aldose reductase inhibitors. SDH: sorbitol dehydrogenase.