The Impact of α-Lipoic Acid Treatment on Multiple Sclerosis Disability: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Abstract
Background: Multiple sclerosis (MS) is a chronic inflammatory disease characterized by demyelination in the central nervous system (CNS). Despite the availability of interventions for disease exacerbations and symptomatic management, EM remained without a cure. Oxidative stress has been implicated in the MS demyelination mechanism. Adjuvant therapies like α-lipoic acid (ALA) have garnered interest for their potential to mitigate oxidative damage and control MS symptoms. ALA is found naturally in vegetables and red meat and can also be synthesized in mitochondria through enzymatic reactions involving octanoic acid and cysteine. However, its bioavailability from dietary sources is limited, prompting an investigation into supplemental forms. We conducted a systematic review and meta-analysis to assess the effect of ALA on disability in randomized clinical trials (RCTs) for MS. Methods: Records were searched until June 2023 (CRD42023397760). Five RCTs evaluated ALA’s effect on MS progression using the Expanded Disability Status Scale (EDSS). The quality of evidence was assessed using GRADE, and publication bias was evaluated using Egger’s and Begg’s tests. Results: Following the selection process, five studies were included involving 179 patients (87 placebo and 92 ALA). Oral administration of racemic ALA (R/S-ALA) at 600 mg twice daily reduced EDSS, indicating a potential for ALA supplementation to mitigate MS disability. The North American trials (SPMS patients) did not show heterogeneity, while Asian studies (RRMS patients) were moderated. The quality of evidence was high without publication bias. Conclusions: ALA treatment reduce EDSS scores. However, further studies are warranted to establish the role of ALA as an adjuvant in clinical practice in long-term follow-up (>2 years) RCTs.
Funding Information
  • Conselho Nacional de Desenvolvimento Científico (CNPq) (200483/2022-6, 303531/2020-7, 401653/2022-6, 88887.501568/2020-00, 88887.501615/2020-00, 21/2551-0001935-2)
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (200483/2022-6, 303531/2020-7, 401653/2022-6, 88887.501568/2020-00, 88887.501615/2020-00, 21/2551-0001935-2)
  • Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) (200483/2022-6, 303531/2020-7, 401653/2022-6, 88887.501568/2020-00, 88887.501615/2020-00, 21/2551-0001935-2)

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