Identification of 102 Correlations between Serum Metabolites and Habitual Diet in a Metabolomics Study of the Prostate, Lung, Colorectal, and Ovarian Cancer Trial

J Nutr. 2020 Apr 1;150(4):694-703. doi: 10.1093/jn/nxz300.


Background: Metabolomics has proven useful for detecting objective biomarkers of diet that may help to improve dietary measurement. Studies to date, however, have focused on a relatively narrow set of lipid classes.

Objective: The aim of this study was to uncover candidate dietary biomarkers by identifying serum metabolites correlated with self-reported diet, particularly metabolites in underinvestigated lipid classes, e.g. triglycerides and plasmalogens.

Methods: We assessed dietary questionnaire data and serum metabolite correlations from 491 male and female participants aged 55-75 y in an exploratory cross-sectional study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Self-reported intake was categorized into 50 foods, food groups, beverages, and supplements. We examined 522 identified metabolites using 2 metabolomics platforms (Broad Institute and Massachusetts General Hospital). Correlations were identified using partial Pearson's correlations adjusted for age, sex, BMI, smoking status, study site, and total energy intake [Bonferroni-corrected level of 0.05/(50 × 522) = 1.9 × 10-6]. We assessed prediction of dietary intake by multiple-metabolite linear models with the use of 10-fold crossvalidation least absolute shrinkage and selection operator (LASSO) regression.

Results: Eighteen foods, beverages, and supplements were correlated with ≥1 serum metabolite at the Bonferroni-corrected significance threshold, for a total of 102 correlations. Of these, only 5 have been reported previously, to our knowledge. Our strongest correlations were between citrus and proline betaine (r = 0.55), supplements and pantothenic acid (r = 0.46), and fish and C40:9 phosphatidylcholine (PC) (r = 0.35). The multivariate analysis similarly found reasonably large correlations between metabolite profiles and citrus (r = 0.59), supplements (r = 0.57), and fish (r = 0.44).

Conclusions: Our study of PLCO participants identified many novel food-metabolite associations and replicated 5 previous associations. These candidate biomarkers of diet may help to complement measures of self-reported diet in nutritional epidemiology studies, though further validation work is still needed.

Keywords: biomarkers; dietary questionnaire; food; metabolites; metabolomics.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Animals
  • Biomarkers / blood
  • Colorectal Neoplasms / blood*
  • Cross-Sectional Studies
  • Diet Records
  • Diet*
  • Female
  • Humans
  • Lung Neoplasms / blood*
  • Male
  • Metabolomics*
  • Middle Aged
  • Ovarian Neoplasms / blood*
  • Prostatic Neoplasms / blood*
  • Surveys and Questionnaires


  • Biomarkers