The association between plasma metabolites and future risk of all-cause mortality
Yingxiao Yan1,2, Einar Smith1, Olle Melander1
1Department of Clinical Science, Lund University, Malmö, Sweden.
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.
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