Alpha-Lipoic Acid and Glucose Metabolism: A Comprehensive Update on Biochemical and Therapeutic Features

Abstract

Alpha-lipoic acid (ALA) is a natural compound with antioxidant and pro-oxidant properties which has effects on the regulation of insulin sensitivity and insulin secretion. ALA is widely prescribed in patients with diabetic polyneuropathy due to its positive effects on nerve conduction and alleviation of symptoms. It is, moreover, also prescribed in other insulin resistance conditions such as metabolic syndrome (SM), polycystic ovary syndrome (PCOS) and obesity. However, several cases of Insulin Autoimmune Syndrome (IAS) have been reported in subjects taking ALA. The aim of the present review is to describe the main chemical and biological functions of ALA in glucose metabolism, focusing on its antioxidant activity, its role in modulating insulin sensitivity and secretion and in symptomatic peripheral diabetic polyneuropathy. We also provide a potential explanation for increased risk for the development of IAS.

The effect of alpha-lipoic acid supplementation on anthropometric, glycemic, lipid, oxidative stress, and hormonal parameters in individuals with polycystic ovary syndrome: a systematic review and meta-analysis of randomized clinical trials

“…According to Jacob et al [ 39 ], intravenous administration of 1,000 mg ALA improved insulin sensitivity and the rate at which the body cleared metabolized insulin in patients with type 2 diabetes mellitus. Additionally, the significant effect of ALA on FBS is because of increased glucose transport activity in skeletal muscles [ 40 , 41 ]. However, it is crucial to acknowledge that the influence of ALA extends beyond skeletal muscles, as it inhibits gluconeogenesis and glucose production in the liver [ 42 , 43 ].…”

Elabela inhibits TRAF1/NF-κB induced oxidative DNA damage to promote diabetic foot ulcer wound healing

“… 48 The small molecule alpha-lipoic acid, which was used to treat diabetic neuropathy, was applied to deal with diabetic microvascular disease as it scavenges ROS and repairs antioxidant proteins. 49 In addition, small peptide molecules have become a research hotspot due to their high biological activity, strong specificity, and weak immunogenicity compared to traditional drugs. Recently, agonists and antagonists targeting the APJ have been reported.…”

Clinically Effective Molecules of Natural Origin for Obesity Prevention or Treatment

“…α-Lipoic acid treatment stimulates PI3K activity and insulin receptor substrate 1 (IRS-1) phosphorylation in 3T3-L1 adipocytes. Insulin receptor substrate phosphorylation involves the activation of further intracellular mediators and, subsequently, GLUT4 translocation; therefore, α-lipoic acid can be considered an insulin mimetic agent since insulin receptor binding and IRS-1 phosphorylation could subsequently lead to GLUT4 translocation, increasing glucose uptake [ 213 ]. α-Lipoic acid also decreases hypothalamic AMPK activity and causes rodent weight loss by reducing food intake and increasing energy expenditure [ 214 ].…”