Manganese Concentrations in Biological Matrices and Amyotrophic Lateral Sclerosis (Als): A Systematic Review and Meta-Analysis Publisher Pubmed



Salehcheh M ; Nikravesh M ; Aghebatbekheir S ; Matin M
Source: Neurological Sciences Published:2026

Abstract

Background: Manganese (Mn) is an essential but neurotoxic trace element implicated in neurodegenerative disorders. Its association with amyotrophic lateral sclerosis (ALS) remains uncertain. We conducted a systematic review and meta-analysis to evaluate whether Mn concentrations differ between ALS patients and healthy controls. Methods: We systematically searched PubMed, EMBASE, Web of Science, and Scopus for observational studies comparing Mn concentrations between ALS patients and healthy controls. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity was assessed with the I² statistic, and publication bias was evaluated by Egger’s test. Results: Twelve studies (446 ALS cases, 652 controls) measuring Mn in blood, serum, cerebrospinal fluid (CSF), hair, urine, toenail, plasma, or tissue were included. The pooled SMD was 0.05 (95% CI: − 0.20 to 0.30; p = 0.68; I² = 71.7%), indicating no significant difference in Mn concentrations. Subgroup analyses by biological matrix and analytical method showed no consistent pattern; meta-regression identified analytical method as a significant source of heterogeneity. Conclusion: No publication bias was detected (Egger’s p = 0.53). Peripheral Mn concentrations do not differ significantly between ALS patients and controls. Future research should employ longitudinal and CNS-targeted approaches, incorporating occupational exposure assessment and standardized analytical protocols. © Fondazione Societa Italiana di Neurologia 2026.