Diurnal variation of metabolites in three individual participants

ABSTRACTThe circadian system influences virtually all biological functions. Understanding the impact of circadian variation on metabolism may provide insight into mechanisms of circadian-associated disorders and guide the implementation of chrono-therapy. Previous research has reported circadian variation in 7–20% of metabolites in human blood. In this study, untargeted metabolomics profiles were measured using blood of two healthy men and one healthy woman, collected every 2 h for up to 48 h under carefully controlled conditions. The pattern of variation of each metabolite over time was examined on each participant separately, using both one- and two-order harmonic models. A total of 100 of 663 metabolites, representing all metabolite categories, showed diurnal rhythmic concentrations that exceeded the Bonferroni threshold (P < 2.5 × 10−5). Overall, peak times of many metabolites were clustered during the afternoon-midnight, including the majority of amino acids, all peptides, all lysolipids and all phos...