Alpha-lipoic acid, also known as thioctic acid or ALA,  is an organosulphuric compound derived from caprylic acid (octanoic acid). It is an antioxidant produced by the body and present in every cell, where it helps transform glucose into energy.

The name defines the structure of the molecule:

• "Alpha-" refers to the position of the functional group in the molecule.
• "Lipoic" is derived from "lipid", indicating that this compound is fat-soluble.
• "Acid-" refers to the presence of a carboxylic acid group (-COOH) in the molecule.

Synthesis in the human body:

• Alpha-lipoic acid is synthesized in the body, but it can also be taken as a supplement or found in foods such as yeast, liver, kidney, spinach, broccoli, and potatoes.
• The synthesis of alpha-lipoic acid in the body involves a complex process that is not fully understood. It is believed to involve the following steps:
• The body uses enzymes to break down caprylic acid (a type of fatty acid) into smaller molecules.
• These smaller molecules are then rearranged and combined to form alpha-lipoic acid.

Chemical synthesis:

Simplified version of the process:

• The process begins with octanoic acid, a medium-chain fatty acid, which is attached to a transfer RNA molecule. This is a crucial step as it primes the octanoic acid for the subsequent steps.
• The octanoic acid is then modified by a series of enzymatic reactions, which include the addition of sulfur atoms to the molecule. These reactions involve enzymes such as lipoic acid synthetase and a few others.
• The sulfur atoms are derived from the amino acid cysteine. The addition of sulfur transforms the octanoic acid into lipoic acid.
• Finally, the newly formed lipoic acid is attached to certain proteins in the cell, which are involved in key metabolic processes.

What it is for and where

Medical

• Antioxidant Support. ALA is known for its antioxidant properties, which can help protect cells from damage caused by free radicals.
• Neuropathy Treatment. ALA has been used to treat peripheral neuropathy, a condition often associated with diabetes that results in numbness, tingling, and pain in the hands and feet.
• Liver Health. ALA plays a role in detoxifying the body, particularly the liver.
• Glucose Metabolism. ALA has been studied for its potential to improve glucose metabolism and thus help manage diabetes.
• Erectile Dysfunction. Some studies suggest that ALA could improve erectile dysfunction in diabetic patients when combined with other treatments.

Cosmetics

Antioxidant agent. Ingredient that counteracts oxidative stress and prevents cell damage. Free radicals, pathological inflammatory processes, reactive nitrogen species and reactive oxygen species are responsible for the ageing process and many diseases caused by oxidation.

• Molecular Formula   C₈H₁₄O₂S₂
• Molecular Weight   206.3 g/mol
• CAS  1077-28-7
• UNII    73Y7P0K73Y
• EC Number   214-071-2

Compendium of the most significant studies with reference to properties, intake, effects.

Salehi B, Berkay Yılmaz Y, Antika G, Boyunegmez Tumer T, Fawzi Mahomoodally M, Lobine D, Akram M, Riaz M, Capanoglu E, Sharopov F, Martins N, Cho WC, Sharifi-Rad J. Insights on the Use of α-Lipoic Acid for Therapeutic Purposes. Biomolecules. 2019 Aug 9;9(8):356. doi: 10.3390/biom9080356.

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.

Di Tucci C, Di Feliciantonio M, Vena F, Capone C, Schiavi MC, Pietrangeli D, Muzii L, Benedetti Panici P. Alpha lipoic acid in obstetrics and gynecology. Gynecol Endocrinol. 2018 Sep;34(9):729-733. doi: 10.1080/09513590.2018.1462320. 

Abstract. Alpha-Lipoic acid (ALA) is a natural antioxidant synthetized by plants and animals, identified as a catalytic agent for oxidative decarboxylation of pyruvate and α-ketoglutarate. In this review, we analyzed the action of ALA in gynecology and obstetrics focusing in particular on neuropathic pain and antioxidant and anti-inflammatory action. A comprehensive literature search was performed in PubMed and Cochrane Library for retrieving articles in English language on the antioxidant and anti-inflammatory effects of ALA in gynecological and obstetrical conditions. ALA reduces oxidative stress and insulin resistance in women with polycystic ovary syndrome (PCOS). The association of N-acetyl cysteine (NAC), alpha-lipoic acid (ALA), and bromelain (Br) is used for prevention and treatment of endometriosis. In association with omega-3 polyunsaturated fatty acids (n-3 PUFAs) with amitriptyline is used for treatment of vestibulodynia/painful bladder syndrome (VBD/PBS). A promising area of research is ALA supplementation in patients with threatened miscarriage to improve the subchorionic hematoma resorption. Furthermore, ALA could be used in prevention of diabetic embryopathy and premature rupture of fetal membranes induced by inflamation. In conclusion, ALA can be safely used for treatment of neuropatic pain and as a dietary support during pregnancy.

Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009 Oct;1790(10):1149-60. doi: 10.1016/j.bbagen.2009.07.026.

Abstract. Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well-defined as a therapy for preventing diabetic polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age. How do the biochemical properties of LA relate to its biological effects? Herein, we review the molecular mechanisms of LA discovered using cell and animal models, and the effects of LA on human subjects. Though LA has long been touted as an antioxidant, it has also been shown to improve glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa B. LA and its reduced form, dihydrolipoic acid, may use their chemical properties as a redox couple to alter protein conformations by forming mixed disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting that some of its therapeutic potential extends beyond the strict definition of an antioxidant. Current trials are investigating whether these beneficial properties of LA make it an appropriate treatment not just for diabetes, but also for the prevention of vascular disease, hypertension, and inflammation.

Rochette L, Ghibu S, Muresan A, Vergely C. Alpha-lipoic acid: molecular mechanisms and therapeutic potential in diabetes. Can J Physiol Pharmacol. 2015 Dec;93(12):1021-7. doi: 10.1139/cjpp-2014-0353. 

Abstract. Diabetes is a chronic metabolic disease with a high prevalence worldwide. Diabetes and insulin resistance are associated with the development of cardiovascular and nervous diseases. The development of these disorders reflects complex pathological processes in which the oxidative stress caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) plays a pivotal role. It is widely accepted that diabetes impairs endothelial nitric oxide synthase (eNOS) activity and increases the production of ROS, thus resulting in diminished NO bioavailability and increased oxidative stress. Alpha-lipoic acid (LA) possesses beneficial effects both in the prevention and in the treatment of diabetes. LA is a potent antioxidant with insulin-mimetic and anti-inflammatory activity. LA in the diet is quickly absorbed, transported to the intracellular compartments, and reduced to dihydrolipoic acid (DHLA) under the action of enzymes. LA, which plays an essential role in mitochondrial bioenergetic reactions, has drawn considerable attention as an antioxidant for use in managing diabetic complications such as retinopathy, neuropathy and other vascular diseases.