Post-traumatic stress disorder, diabetes mellitus, and alpha-lipoic acid

Post-traumatic stress disorder (PTSD) is a prognostic factor for the development of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), increases the risk of cardiometabolic pathologies and neurodegenerative diseases. At the same time, T2DM and MetS can also cause the development of major neurosis-like and psychiatric symptoms characteristic of PTSD. Their influence can manifested through negative effects on the central nervous system, in particular the development of neurodegenerative diseases. Oxidative stress and chronic low-grade inflammation play an important role in the pathophysiology of PTSD, MetS, and T2DM, making them the main therapeutic targets. Targeted effects on oxidative stress, chronic low-grade inflammation and mitochondrial metabolism disorders, the use of antioxidants, in particular α-lipoic acid (ALA), can positively affect not only the course of comorbidities but also the main manifestations of PTSD. In vitro and in vivo studies have demonstrated that ALA modulates a number of pathways associated with oxidative stress. In addition, the results of clinical trials confirm the antioxidant mechanism of ALA action in patients with obesity, MetS, diabetes type 1 and 2. The neuroprotective activity of ALA is being actively studied and is proving promising as a therapeutic approach in the treatment of PTSD and neurodegenerative diseases. Despite the significant therapeutic potential of ALA, its clinical application is limited by several significant barriers. In particular, clinical trials lack standardized treatment protocols, as well as a detailed assessment of the effectiveness of ALA alone. In addition, the pharmacokinetic profile of ALA remains limited, which is one of the main factors that hinder its use. In this context, there are certain prospects for the development of ALA transportation systems based on nanoparticles, which can potentially solve a number of these problems. In addition, the technologies of so­lid lipid nanoparticles such as niosomes, liposomes, nanostructured lipid carriers and micelles provide the possibility of local or systemic use of ALA. However, further preclinical and clinical studies are needed to definitively determine the clinical feasibility and therapeutic potential of ALA. The search was conducted in Scopus, Science Direct (from Elsevier) and PubMed, including MEDLINE databases. The keywords used were “α-lipoic acid”, “post-traumatic stress disorder”, “diabetes mellitus”, “metabolic syndrome”. A manual search of the bibliography of publications was used to identify study results that could not be found during the online search.