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

ABSTRACT

Introduction: 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.

KEYWORDS:

• Alpha-lipoic acid
• antioxidant activity
• drug delivery
• gynecology
• immunomodulation
• inflammation
• miscarriage
• NF-kB
• Nrf2
• subchorionic hematoma
• vaginal route

Article highlights

• Alpha-lipoic acid (ALA) is an organosulfur compound playing a pivotal role as cofactor within α-keto-acid dehydrogenase complexes and glycine cleavage system.

• In living organisms, ALA is present either in its reduced, as dihydrolipoic acid (DHLA), and oxidized, disulfuric form.

• ALA is synthesized in plants and animals, but its production in humans is very low.

• ALA and DHLA play a key role in a large amount of physiological processes, exerting antioxidant, anti-inflammatory and detoxifying activities. On the whole the result is a fine immunomodulatory effect.

• ALA can be used efficaciously as drug or dietary supplement.

• ALA has been demonstrated to be safe at therapeutic doses.

• ALA and DHLA rescue altered physiological balance without negatively affecting other cascades of metabolic events not involved in pathological alterations.

• ALA treatment is effective in improving many diseases, such as cancer, sepsis, insulin resistance and diabetes, neurodegenerative disorders and neuropathy, ischemia-reperfusion injury, tissue regeneration, aging.

• Two recent clinical studies demonstrated that ALA administered by oral or vaginal route can also significantly contribute to speed up the healing process of subchorionic hematomas related to threatened miscarriage.

• ALA biological properties and the first therapeutic results obtained in miscarriage prevention suggest a promising application of this molecule also in gynecology; this research area deserves an in-depth investigation.

This box summarizes the key points contained in the article.

Declaration of interest

V Unfer and S De Grazie are employees at LO.LI.Pharma, Rome, Italy. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.