Abstract Background Postprandial metabolomic profiles and their inter-individual variability are not well characterised. Here we describe postprandial metabolite changes, their correlations with fasting values and their inter- and intra-individual variability following a standardised meal in the ZOE PREDICT 1 cohort. Methods In the ZOE PREDICT 1 study ( n = 1,002 ( NCT03479866 )), 250 metabolites, mainly lipids, were measured by Nightingale NMR panel in fasting and postprandial (4 and 6 h after a 3.7 MJ mixed nutrient meal, with a second 2.2 MJ mixed nutrient meal at 4 h) serum samples. For each metabolite, inter- and intra-individual variability over-time was evaluated using linear mixed modelling and intraclass-correlation coefficients (ICC) calculated. Results Postprandially, 85% (of 250 metabolites) significantly changed from fasting at 6h (47% increased, 53% decreased; Kruskal-Wallis), with 37 measures increasing by &gt;25%, and 14 increasing by &gt;50%. The largest changes were observed in very large lipoprotein particles and ketone bodies. Seventy-one percent of circulating metabolites were strongly correlated (Spearman’s rho &gt;0.80) between fasting and postprandial timepoints, and 5% were weakly correlated (rho &lt;0.50). The median ICC of the 250 metabolites was 0.91 (range 0.08-0.99). The lowest ICCs (ICC&lt;0.40, 4% of measures) were found for glucose, pyruvate, ketone bodies (β-hydroxybutyrate, acetoacetate, acetate) and lactate. Conclusions In this large-scale postprandial metabolomic study, circulating metabolites were highly variable between individuals following a mixed challenge meal. Findings suggest that a meal challenge may yield postprandial responses divergent from fasting measures, specifically for glycolysis, essential amino acid, ketone body and lipoprotein size metabolites.

Characterisation of fasting and postprandial NMR metabolites: insights from the ZOE PREDICT 1 Study