ABSTRACT
Background@#Amyotrophic lateral sclerosis is one of the neurodegenerative disorders with very limited treatment options owing to its progressive course and diverse pathophysiology. Majority of patients succumb to death within three to five years after the onset of symptoms, mostly due to respiratory failure. This study aimed to determine the efficacy and safety of ultra-high dose methylcobalamin versus placebo among patients with early-stage amyotrophic lateral sclerosis in terms of slowing down functional decline.@*Methods@#MEDLINE, CENTRAL, and Google Scholar databases were searched from inception up to September 23, 2023. The impact of treatments was measured by risk ratios with 95% confidence interval. The overall certainty of the evidence was evaluated using GRADE. @*Results@#No significant difference was detected for the outcome median change in the ALSFRS-R score for the whole cohort. Post-hoc analyses showed that ultra-high-dose methylcobalamin decreased ALSFRS-R scores (p=0.003 for 50 mg and p=0.01 for all methylcobalamin groups) in a dose-responsive manner. Mean difference was 1.97 in favor of methylcobalamin (95% CI, 0.44- 3.50; P = .01).@*Conclusion@#Ultra-high dose methylcobalamin can reduce ALSFRS-R scores of patients in its early stage but the scarcity of clinical trials makes it difficult to support a robust conclusion. Ultra-high dose methylcobalamin therapy remains to be investigational.