Acido tioctico o acido alfa-lipoico, noto anche come acido tioctico o come ALA, è un composto organosolforico derivato dall'acido caprilico (acido ottanoico). È un antiossidante prodotto dall'organismo e presente in ogni cellula, dove aiuta a trasformare il glucosio in energia.

Il nome definisce la struttura della molecola:

"Acido tioctico" è la traduzione italiana di "thioctic acid" o "alpha-lipoic acid". 

Analizziamo il nome:

• Acido sta per "acid". In chimica, un acido è una sostanza che può donare un protone (H+) in una reazione.
• tioctico sta per "thioctic". Il prefisso "tio-" deriva dalla parola italiana per zolfo, "zolfo", e indica la presenza di zolfo nella molecola. La parte "-octico" deriva da "ottanoico", che è la parola italiana per "octanoic". L'acido ottanoico è un tipo di acido grasso con una catena di otto atomi di carbonio.

Sintesi nel corpo umano:

• L'acido alfa-lipoico viene sintetizzato dall'organismo, ma può anche essere assunto come integratore o contenuto in alimenti come lievito, fegato, reni, spinaci, broccoli e patate.
• La sintesi dell'acido alfa-lipoico nell'organismo comporta un processo complesso che non è ancora del tutto chiaro. Si ritiene che comporti le seguenti fasi:
• L'organismo utilizza degli enzimi per scomporre l'acido caprilico (un tipo di acido grasso) in molecole più piccole.
• Queste molecole più piccole vengono poi riorganizzate e combinate per formare l'acido alfa-lipoico.

Sintesi chimica:

Cersione semplificata del processo:

• Il processo inizia con l'acido ottanoico, un acido grasso a catena media, che viene attaccato a una molecola di RNA transfer. Questo è un passaggio cruciale, in quanto prepara l'acido ottanoico per le fasi successive.
• L'acido ottanoico viene poi modificato da una serie di reazioni enzimatiche, che comprendono l'aggiunta di atomi di zolfo alla molecola. Queste reazioni coinvolgono enzimi come l'acido lipoico sintetasi e alcuni altri.
• Gli atomi di zolfo derivano dall'aminoacido cisteina. L'aggiunta di zolfo trasforma l'acido ottanoico in acido lipoico.
• Infine, l'acido lipoico appena formato si lega ad alcune proteine della cellula, coinvolte in processi metabolici chiave.

A cosa serve e dove si usa

Medicina

• Supporto antiossidante. L'ALA è noto per le sue proprietà antiossidanti, che possono aiutare a proteggere le cellule dai danni causati dai radicali liberi.
• Trattamento della neuropatia. L'ALA è stato utilizzato per trattare la neuropatia periferica, una condizione spesso associata al diabete che provoca intorpidimento, formicolio e dolore alle mani e ai piedi.
• Salute del fegato. L'ALA svolge un ruolo di disintossicazione dell'organismo, in particolare del fegato.
• Metabolismo del glucosio. L'ALA è stato studiato per il suo potenziale di miglioramento del metabolismo del glucosio e quindi di aiuto nella gestione del diabete.
• Disfunzione erettile. Alcuni studi suggeriscono che l'ALA potrebbe migliorare la disfunzione erettile nei pazienti diabetici se associato ad altri trattamenti.

Cosmetica

Agente antiossidante. Ingrediente che contrasta lo stress ossidativo e che evita danni cellulari. I radicali liberi, i processi infiammatori patologici, le specie reattive dell'azoto e le specie reattive dell'ossigeno sono responsabili del processo di invecchiamento e di molte malattie causate dall'ossidazione.

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

Compendio degli studi più significativi con riferimento a proprietà, assunzione, effetti.

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.