Lipoic Acid as a Potential Therapy for Chronic Diseases Associated with Oxidative Stress

A.   R.   Smith; S.   V.   Shenvi; M.      Widlansky; J.   H.   Suh; T.   M.   Hagen

doi:10.2174/0929867043365387

Abstract

α-Lipoic acid (LA), a naturally occurring dithiol compound, has long been known as an essential cofactor for mitochondrial bioenergetic enzymes. Aside from its enzymatic role, in vitro and in vivo studies suggest that LA also acts as a powerful micronutrient with diverse pharmacologic and antioxidant properties. Pharmacolo-gically, LA improves glycemic control, polyneuropathies associated with diabetes mellitus, and effectively mitigates toxicities associated with heavy metal poisoning. As an antioxidant, LA directly terminates free radicals, chelates transition metal ions (e.g. iron and copper), increases cytosolic glutathione and vitamin C levels and prevents toxicities associated with their loss. These diverse actions suggest that LA acts by multiple mechanisms both physiologically and pharmacologically, many of which are only now being explored. Herein, we review the known biochemical properties of LA with particular reference to how LA may be an effective agent to ameliorate certain pathophysiologies of many chronic diseases.

Keywords: lipoic acid, dihydrolipoic acid, diabetes, signal transduction, dithiol, oxidative stress, antioxidants, polyneuropathy, redox, metal chelation