The association between plasma metabolites and future risk of all-cause mortality

Journal article, 2022

Background: Metabolite profiles provide snapshots of the overall effect of numerous exposures accumulated over life courses, which may lead to health outcomes in the future.
Objective: We hypothesized that the risk of all-cause mortality is linked to alterations in metabolism earlier in life, which are reflected in plasma metabolite profiles. We aimed to identify plasma metabolites associated with future risk of all-cause mortality.
Methods: Through metabolomics, 110 metabolites were measured in 3833 individuals from the Malmö Diet and Cancer—Cardiovascular Cohort (MDC-CC). A total of 1574 deaths occurred within an average follow-up time of 22.2 years. Metabolites that were significantly associated with all-cause mortality in MDC-CC were replicated in 1500 individuals from Malmö Preventive Project re-examination (MPP), among whom 715 deaths occurred within an average follow-up time of 11.3 years.
Results: Twenty two metabolites were significantly associated with all-cause mortality in MDC-CC, of which 13 were replicated in MPP. Levels of trigonelline, glutamate, dimethylglycine, C18-1-carnitine, C16-1-carnitine, C14-1-carnitine, and 1-methyladenosine were associated with an increased risk, while levels of valine, tryptophan, lysine, leucine, histidine, and 2-aminoisobutyrate were associated with a decreased risk of all-cause mortality. Conclusion: We used metabolomics in two Swedish prospective cohorts and identified replicable associations between 13 metabolites and future risk of all-cause mortality. Novel associations between five metabolites—C18-1-carnitine, C16-1-carnitine, C14-1-carnitine, trigonelline, and 2-aminoisobutyrate—and all-cause mortality were discovered. These findings suggest potential new biomarkers for the prediction of mortality and provide insights for understanding the biochemical pathways that lead to mortality.