Charged metabolite biomarkers of food intake assessed via plasma metabolomics in a population-based observational study in Japan

PLoS One. 2021 Feb 10;16(2):e0246456. doi: 10.1371/journal.pone.0246456. eCollection 2021.


Food intake biomarkers can be critical tools that can be used to objectively assess dietary exposure for both epidemiological and clinical nutrition studies. While an accurate estimation of food intake is essential to unravel associations between the intake and specific health conditions, random and systematic errors affect self-reported assessments. This study aimed to clarify how habitual food intake influences the circulating plasma metabolome in a free-living Japanese regional population and to identify potential food intake biomarkers. To achieve this aim, we conducted a cross-sectional analysis as part of a large cohort study. From a baseline survey of the Tsuruoka Metabolome Cohort Study, 7,012 eligible male and female participants aged 40-69 years were chosen for this study. All data on patients' health status and dietary intake were assessed via a food frequency questionnaire, and plasma samples were obtained during an annual physical examination. Ninety-four charged plasma metabolites were measured using capillary electrophoresis mass spectrometry, by a non-targeted approach. Statistical analysis was performed using partial-least-square regression. A total of 21 plasma metabolites were likely to be associated with long-term food intake of nine food groups. In particular, the influential compounds in each food group were hydroxyproline for meat, trimethylamine-N-oxide for fish, choline for eggs, galactarate for dairy, cystine and betaine for soy products, threonate and galactarate for carotenoid-rich vegetables, proline betaine for fruits, quinate and trigonelline for coffee, and pipecolate for alcohol, and these were considered as prominent food intake markers in Japanese eating habits. A set of circulating plasma metabolites was identified as potential food intake biomarkers in the Japanese community-dwelling population. These results will open the way for the application of new reliable dietary assessment tools not by self-reported measurements but through objective quantification of biofluids.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Cohort Studies
  • Cross-Sectional Studies
  • Eating*
  • Feeding Behavior
  • Female
  • Humans
  • Japan
  • Male
  • Metabolome
  • Metabolomics / methods*
  • Middle Aged


  • Biomarkers

Grant support

This work was supported in part by research funds from the Yamagata Prefectural Government ( and the city of Tsuruoka ( and by the Grant-in-Aid for Scientific Research (B) (grant numbers JP24390168, JP15H04778) and Grant-in-Aid for Challenging Exploratory Research (grant number 25670303) from the Japan Society for the Promotion of Science ( The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.