Therapy with antioxidants in human diabetic neuropathy

Increased oxidative stress has been implicated in the pathogenesis of diabetic polyneuropathy (DPN). Antioxidant treatment with alpha-lipoic acid (ALA) has been shown to prevent or ameliorate experimental diabetic neuropathy, providing the rationale for treatment in humans. A recent meta-analysis including four controlled clinical trials provided evidence that treatment with ALA (600 mg/day i.v.) over 3 weeks is safe and significantly improves both neuropathic symptoms and deficits to a clinically meaningful degree in patients with symptomatic DPN. Moreover, oral treatment for 4–7 months tends to ameliorate neuropathic deficits and cardiac autonomic neuropathy. Clinical and postmarketing surveillance studies have revealed a highly favorable safety profile of this drug. Based on these findings, a pivotal long-term multicenter trial of oral treatment with ALA (NATHAN 1 Study) is under way aimed at slowing the progression of DPN.