8283649 Impact of night-shift work on blood metabolomics in the EPHOR night-shift work study

<h3>Objective</h3> To examine the association between night-shift work and perturbations in blood metabolomics. <h3>Methods</h3> The EPHOR study recruited night-shift and day shift workers mainly from healthcare across The Netherlands (n=98), Spain (n=386), Sweden (n=170), and Denmark (n=196). Blood metabolites were analyzed using the Nightingale Health platform. Linear mixed models, with a random intercept for study center, were used to explore associations between metabolite levels and night-shift work. Principal Component Analysis was conducted within metabolite classes (lipids, amino acids, fatty acids, key energy-related metabolites) to derive metabolic groups. Similar mixed models were used to examine the association between extracted individual scores from each component and night-shift. Analyses were adjusted for potential confounders including age, sex, origin, marital status, education, occupation, smoking, alcohol intake, physical activity, BMI, and chronotype. The False Discovery Rate was applied to account for multiple testing. <h3>Results</h3> Compared to day workers, night-shift workers showed higher saturated fatty acid% (β = 0.50, 95% CI 0.23 to 0.77) and lower linoleic acid% (β = -0.63, CI -1.07 to -0.19), docosahexaenoic acid (DHA)% (β = -0.109, CI -0.19 to -0.03), and total polyunsaturated fatty acid (PUFA)% (β = -0.60, CI -1.06 to -0.14). Scores from a ‘key energy-related metabolites’ component (characterized by high loadings from acetoacetate and acetone) were elevated among night-shift workers (β = 0.36, CI 0.14 to 0.58). In contrast, scores from a fatty acid profile (with high loadings from unsaturation index, PUFA/MUFA, DHA) (β = -0.33, CI -0.57 to -0.08) and an amino acid profile (with high loadings from histidine and glycine) (β = -0.14, CI -0.28 to -0.00) were lower among night-shift workers. <h3>Conclusion</h3> Night-shift work was associated with higher levels of saturated fats and ketone bodies, and lower polyunsaturated fats and specific amino acids. These findings may reflect physiological stress differences between night- and day-shift workers.