Insights on the Use of α-Lipoic Acid for Therapeutic Purposes

Abstract

α-lipoic acid (ALA, thioctic acid) is an organosulfur component produced from plants, animals, and humans. It has various properties, among them great antioxidant potential and is widely used as a racemic drug for diabetic polyneuropathy-associated pain and paresthesia. Naturally, ALA is located in mitochondria, where it is used as a cofactor for pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase complexes. Despite its various potentials, ALA therapeutic efficacy is relatively low due to its pharmacokinetic profile. Data suggests that ALA has a short half-life and bioavailability (about 30%) triggered by its hepatic degradation, reduced solubility as well as instability in the stomach. However, the use of various innovative formulations has greatly improved ALA bioavailability. The R enantiomer of ALA shows better pharmacokinetic parameters, including increased bioavailability as compared to its S enantiomer. Indeed, the use of amphiphilic matrices has capability to improve ALA bioavailability and intestinal absorption. Also, ALA’s liquid formulations are associated with greater plasma concentration and bioavailability as compared to its solidified dosage form. Thus, improved formulations can increase both ALA absorption and bioavailability, leading to a raise in therapeutic efficacy. Interestingly, ALA bioavailability will be dependent on age, while no difference has been found for gender. The present review aims to provide an updated on studies from preclinical to clinical trials assessing ALA’s usages in diabetic patients with neuropathy, obesity, central nervous system-related diseases and abnormalities in pregnancy.

Efficacy and Safety of the Combination of Superoxide Dismutase, Alpha Lipoic Acid, Vitamin B12, and Carnitine for 12 Months in Patients with Diabetic Neuropathy

“…ALA is a medium chain fatty acid, naturally derived from plants and animals, Ref. [ 76 ] with potential antioxidant action and effective in the management of microvascular complications in diabetic rats, such as neuropathy, retinopathy, and other vascular disease [ 33 ]. The Neurological Assessment of Thioctic Acid in Diabetic Neuropathy trial (NATHAN) 1, the longest and largest multi-center, randomized, double-blind, parallel-group trial in patients with uncontrolled diabetes and DPN, showed a favorable effect of a daily dose of 600 mg ALA orally for four years on neuropathic symptoms but not in conduction velocity [ 77 , 78 ].…”

Higher Epoxyeicosatrienoic Acids in Cardiomyocytes-Specific CYP2J2 Transgenic Mice Are Associated with Improved Myocardial Remodeling

“…A couple of available cardiac therapies are dietary supplementation of α-lipoic acid (ALA) and cardiac resynchronization therapy (CRT). ALA, an enzymatic cofactor involved in energy production and mitochondrial biogenesis, has antioxidant and anti-inflammatory properties [ 33 ]. Dietary supplementation of ALA in two mouse models for human atherosclerosis exhibited significant reduction in atherosclerotic lesion formation [ 34 ].…”

An Overview of the Antioxidant Effects of Ascorbic Acid and Alpha Lipoic Acid (in Liposomal Forms) as Adjuvant in Cancer Treatment

“…Another proposed mechanism of apoptosis and cell death induced by ALA is its remarkable antioxidant effect, accompanied with the ROS scavenging effect, observed in breast cancer cell lines [17,65]. As previously stated, increased production of ROS has been recognised in cancer cell progression due to an increased rate of cell division, metabolic activity and malfunction of intrinsic antioxidant [17,48,65,70]. It was also reported that ALA induced autophagy via inhibition of O6-methylguanine-DNA methyltransferase (MGMT) protein, which consequently led to apoptosis and cytotoxicity to chemo-resistant colorectal cancer cells [71,72].…”

“…Previous studies showed that the intercellular redox balance is linked with the cellular growth and plays a critical role in carcinogenesis. ALA was proposed to reduce elevated oxidative stress accumulated by cancerous cells, leading to apoptosis and inhibition of cell proliferation [45][46][47][48].…”