Abstract
Lipoic acid (LA) is an endogenous antioxidant that exists widely in nature. Supplementation with LA is a promising approach to improve the outcomes of patients with multiple sclerosis (MS). This systematic review aimed to provide a comprehensive overview of both in vitro and in vivo studies describing the pharmacokinetics, efficacy, safety, and mechanism of LA in MS-related experiments and clinical trials. A total of 516 records were identified by searching five databases, including PubMed, Web of Science, Embase, Scopus, and Cochrane Library. Overall, we included 20 studies reporting LA effects in cell and mouse models of MS and 12 studies reporting LA effects in patients with MS. Briefly, cell experiments revealed that LA protected neurons by inhibiting the expression of inflammatory mediators and activities of immune cells. Experimental autoimmune encephalomyelitis mouse experiments demonstrated that LA consistently reduced the number of infiltrating immune cells in the central nervous system and decreased the clinical disability scores. Patients with MS showed relatively stable Expanded Disability Status Scale scores and better walking performance with few adverse events after the oral administration of LA. Notably, heterogeneity of this evidence existed among modeling methods, LA usage, MS stage, and trial duration. In conclusion, this review provides evidence for the anti-inflammatory and antioxidative effects of LA in both in vitro and in vivo experiments; therefore, patients with MS may benefit from LA administration. Whether LA can be a routine supplementary therapy warrants further study.