Survivors with chronic sequelae of carbon monoxide (CO) poisoning after the 1963 Miike-Mikawa coal mine disaster can exhibit persistent higher brain dysfunction in late life. We examined whether serum Show more
Survivors with chronic sequelae of carbon monoxide (CO) poisoning after the 1963 Miike-Mikawa coal mine disaster can exhibit persistent higher brain dysfunction in late life. We examined whether serum metabolic alterations remained detectable ~60 years later and assessed serum brain-derived neurotrophic factor (BDNF). In this cross-sectional case-control study, outpatients with chronic CO-poisoning sequelae (CO; n = 14) and former miners without CO exposure (CON; n = 16), all aged ≥ 75 years, underwent targeted serum metabolomics (1183 metabolites) and clinical assessments. Between-group differences were evaluated using Welch's Relative to controls, the CO group showed higher valine, alanine, and betaine and lower 3-hydroxybutyric acid, inosine, and hypoxanthine; these contrasts persisted with concordant direction after matching. Serum BDNF was lower in the CO group (unadjusted trend) and was significantly reduced after age/MMSE adjustment ( Six decades after exposure, chronic CO sequelae were associated with a reproducible serum profile combining amino-acid elevations with relative suppression of ketone-body and purine-related metabolites, suggesting enduring alterations in systemic substrate handling and bioenergetics. If replicated in larger cohorts, such signatures-potentially alongside BDNF-should be regarded as hypothesis-generating; biomarker development would require external validation, longitudinal tracking, and assessment of intervention responsiveness before any clinical use is considered. Show less