Role of Folate Metabolism in Neurodegenerative Diseases: Insight from Experimental and Clinical Studies.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing preclinical and clinical studies without systematic review methodology
PubMed 42043709 · doi:10.1007/s13668-026-00761-5
What was done
This narrative review synthesized experimental and clinical findings investigating the role of folate-mediated one-carbon metabolism dysregulation across neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Huntington's disease.
What was found
The abstract reports no numerical data, effect sizes, or statistical metrics. It describes qualitative mechanistic pathways where folate deficiency and elevated homocysteine are associated with amyloid-beta accumulation, tau pathology, oxidative stress, impaired methylation, mitochondrial dysfunction, neuroinflammation, and dopaminergic neuronal loss. Clinical folate supplementation outcomes in Alzheimer's disease were reported as mixed, while combined folate and vitamin B12 supplementation was noted as potentially reducing levodopa-associated risks in Parkinson's disease.
Why it matters
The review organizes the biological and clinical pathways connecting one-carbon metabolism to multiple neurodegenerative disorders. It highlights that despite clear mechanistic connections, interventional clinical evidence supporting folate supplementation remains inconclusive.
Limits
As a narrative review, it lacks systematic search criteria, risk-of-bias evaluation, and quantitative pooling. The abstract provides no specific sample sizes, demographic details, optimal therapeutic dosages, or detailed breakdown of conflicting trial outcomes.
Cited by
- supports Inflammation, methylation imbalances, and oxidative stress are key drivers of brain dysfunction and neurodegeneration.