Immunomodulatory activities of alpha lipoic acid with a special focus on its efficacy in preventing miscarriage

Abstract

Alpha lipoic acid (ALA) is an essential mitochondrial co-factor and, as a free molecule, it can exert multi-level immunomodulatory functions. Both ALA and its reduced form, dihydrolipoic acid (DHLA), are believed to be able to chelate heavy metals, to regenerate essential antioxidants and to repair important molecules damaged by oxidation. The largest part of the effects of ALA/DHLA couple can be explained by a specific stimulatory activity on Nrf2-dependent gene transcription and by the inhibition of NF-kB activity. These features have prompted its use as a drug for several diseases. Areas covered: This article surveys the main features of ALA/DHLA and its therapeutic effects. Its complex and differentiated function cannot simply be reduced to anti-inflammatory, antioxidant and detoxifying action. We highlight its capability to finely modulate several physiological pathways when unbalanced. In particular, we focus our attention on pregnancy, in relation to ALA administration by oral route and by a new formulation for vaginal delivery, in patients with threatened miscarriage. Expert opinion: Future efforts should be devoted to explaining carefully ALA/DHLA mechanism of action to reactivate the physiological balance when modified during pregnancy. On the other hand, ALA safety in pregnant women and its pharmacokinetics by vaginal route, have to be studied in depth. Moreover, ALA efficacy has to be confirmed in a much larger sample of patients.

Inositol and antioxidant supplementation: Safety and efficacy in pregnancy

“…α‐Lipoic acid (LA) is a potent biological antioxidant and a naturally occurring cofactor of mitochondrial dehydrogenase complexes . It is believed to directly scavenge ROS and reactive nitrogen species (RNS), both in vitro and in vivo . LA regenerates essential antioxidant molecules, ie, coenzyme Q10, vitamin C, vitamin E, etc and chelates several heavy metals involved in oxidative processes .…”

Reduction in maternal serum values of glucose and gamma‐glutamyltransferase after supplementation with alpha‐lipoic acid in women with gestational diabetes mellitus

“…ALA can induce expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) which is a key transcription factor for expression of some antioxidants’ genes such as glutathione synthesis pathway. On the other hand, ALA can inhibit nuclear factor‐κB which is an inhibitor of Nrf2 …”

Alpha-lipoic acid: mechanisms of action and beneficial effects in the prevention and treatment of diabetic complications

“…In addition to PKCδ, ALA activates extracellular signal-regulated kinase 1/2 (Erk1/2), p38 MAPK, phosphatidylinositol-4,5-bisphosphate 3 (PI3)-kinase, and protein kinase B (Akt). 24,25 Alpha-lipoic acid is effective in reducing OS by preventing LPO and protein damage as other antioxidants significantly inhibit the ROS such as proxy nitrite, NO, hydroxyl radicals, superoxide anion in the membrane and aquatic environment. 9 Antioxidant action of ALA is mediated by two essential nuclear factors: Nrf2 and NF-kB.…”