Beneficial effects of alpha-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: Relationto parameters of oxidative stress

The impairment of nitric oxide (NO)-mediated vasodilation in diabetes has b een attributed to increased vascular oxidative stress. Lipoic acid has been shown to have substantial antioxidative properties. The aim of this study was to assess the effect of lipoic acid on NO-mediated vasodilation in diab etic patients in comparison with the well-recognized effect of ascorbic aci d. Using venous occlusion plethysmography, we examined the effects of lipoi c acid (0.2 mM) and ascorbic acid (1 and 10 mM) on forearm blood flow respo nses to acetylcholine. sodium nitroprusside and concomitant infusion of the NO-inhibitor, N-G-monomethyl-L-arginine, in 39 diabetic patients and 11 co ntrol subjects. Plasma levels of antioxidants and parameters of lipid perox idation were measured and correlated to endothelial function tests. Lipoic acid improved NO-mediated vasodilation in diabetic patients, but not in con trols. NO-mediated vasodilation was improved by ascorbic acid at 10 mM, but not 1 mM. Improvements of endothelial function by ascorbic acid and lipoic acid were closely related. The beneficial effects of lipoic acid were posi tively related to plasma levels of malondialdehyde and inversely related to levels of ubiquinol-10. These findings support the concept that oxidative stress contributes to endothelial dysfunction and suggest a therapeutic pot ential of lipoic acid particularly in patients with imbalance between incre ased oxidative stress and depleted antioxidant defense. (C) 2001 Elsevier S cience Inc.