α-lipoic acid in the treatment of diabetic polyneuropathy and Alzheimer’s disease

Abstract

α-lipoic acid (LA) is a naturally occurring cofactor for mitochondrial enzymes, including pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KGDH). LA acts as a powerful micronutrient with diverse pharmacological properties. LA improves glucose uptake and insulin sensitivity, and thus decreases blood glucose levels and increases mitochondrial energy levels. LA chelates redox-active transition metals, thus inhibiting the formation of hydroxyl radicals from hydrogen peroxide and also scavenges reactive oxygen species, thereby increasing the levels of reduced glutathione. Via the same mechanisms, down-regulation of redox-sensitive inflammatory processes is achieved. Furthermore, LA can scavenge lipid peroxidation products such as hydroxynonenal and acrolein. LA is currently studied for the treatment of some neurodegenerative diseases with diverse pathophysiology, including diabetic polyneuropathy and Alzheimer’s disease. For diabetic polyneuropathy, LA has been used for decades in Germany with a number of clinical trials showing benefits in insulin-stimulated glucose uptake and attenuating symptoms of neuropathy. In Alzheimer’s disease, an open-label trial in patients with mild and moderate Alzheimer’s disease is currently conducted at a at the memory clinic of the Henriettenstiftung hospital in Hannover, Germany. Interim analysis of the data after 4 years show that the progression rate of the patient treated with 600 mg LA daily is significantly slower than to the non-treated control group - particularly in early stages of dementia - and other control groups in published studies.