Relationships among nitrous oxide exposure, neurological injury and biomarkers.
British journal of clinical pharmacology July 20, 2026 Laxna Bhujel, Angela L Chiew, Bhashita Jagarlamudi et al.
Higher cumulative recreational nitrous oxide (N2O) exposure is the strongest predictor of severe neurological outcomes, showing a dose-dependent relationship with neurotoxicity. In a retrospective cohort study of 81 individuals hospitalized across six Sydney hospitals from 2020 to 2025, greater cumulative N2O exposure was associated with worse neurological impairment, including subacute combined degeneration of the spinal cord and peripheral neuropathy, and correlated with greater neuropathy severity. Median homocysteine was 50 μmol/L and median methylmalonic acid (MMA) was 0.68 μmol/L. Homocysteine and MMA were sensitive markers associated with neurological toxicity, making them useful screening biomarkers, but their limited specificity reduces utility as confirmatory tests. B12 and holotranscobalamin showed high specificity but low sensitivity for detecting cases with spinal cord degeneration.