# Sixty Years After a Coal Mine Disaster: Serum Metabolomic Profiles in Older Adults with Long-Term Sequelae of Carbon Monoxide Poisoning: A Cross-Sectional Study

## TL;DR

This study found that people who survived a 1963 coal mine disaster still have distinct metabolic profiles in their blood decades later, suggesting long-term effects of carbon monoxide poisoning on brain and body function.

## Contribution

The study identifies a reproducible serum metabolomic profile in CO poisoning survivors 60 years post-exposure, linking it to altered amino acids and bioenergetics.

## Key findings

- CO group had higher valine, alanine, and betaine compared to controls.
- CO group showed lower levels of 3-hydroxybutyric acid, inosine, and hypoxanthine.
- Serum BDNF was significantly reduced in the CO group after adjusting for age and cognitive function.

## Abstract

Background: 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). Methods: 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 t-test, and age-matched propensity-score matching (1:1) served as a sensitivity analysis. BDNF was additionally compared using a linear regression/ analysis of covariancemodel adjusting for age and Mini–Mental State Examination (MMSE). Results: 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 (p = 0.0252). Exploratory correlations between clinical measures and selected metabolites/BDNF were attenuated after accounting for group. Conclusions: 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.