Comparing metabolite profiles of habitual diet in serum and urine

Am J Clin Nutr. 2016 Sep;104(3):776-89. doi: 10.3945/ajcn.116.135301. Epub 2016 Aug 10.


Background: Diet plays an important role in chronic disease etiology, but some diet-disease associations remain inconclusive because of methodologic limitations in dietary assessment. Metabolomics is a novel method for identifying objective dietary biomarkers, although it is unclear what dietary information is captured from metabolites found in serum compared with urine.

Objective: We compared metabolite profiles of habitual diet measured from serum with those measured from urine.

Design: We first estimated correlations between consumption of 56 foods, beverages, and supplements assessed by a food-frequency questionnaire, with 676 serum and 848 urine metabolites identified by untargeted liquid chromatography mass spectrometry, ultra-high performance liquid chromatography tandem mass spectrometry, and gas chromatography mass spectrometry in a colon adenoma case-control study (n = 125 cases and 128 controls) while adjusting for age, sex, smoking, fasting, case-control status, body mass index, physical activity, education, and caloric intake. We controlled for multiple comparisons with the use of a false discovery rate of <0.1. Next, we created serum and urine multiple-metabolite models to predict food intake with the use of 10-fold crossvalidation least absolute shrinkage and selection operator regression for 80% of the data; predicted values were created in the remaining 20%. Finally, we compared predicted values with estimates obtained from self-reported intake for metabolites measured in serum and urine.

Results: We identified metabolites associated with 46 of 56 dietary items; 417 urine and 105 serum metabolites were correlated with ≥1 food, beverage, or supplement. More metabolites in urine (n = 154) than in serum (n = 39) were associated uniquely with one food. We found previously unreported metabolite associations with leafy green vegetables, sugar-sweetened beverages, citrus, added sugar, red meat, shellfish, desserts, and wine. Prediction of dietary intake from multiple-metabolite profiles was similar between biofluids.

Conclusions: Candidate metabolite biomarkers of habitual diet are identifiable in both serum and urine. Urine samples offer a valid alternative or complement to serum for metabolite biomarkers of diet in large-scale clinical or epidemiologic studies.

Keywords: biomarker; diet; food; metabolite; metabolomics; nutrition assessment; serum; urine.

Publication types

  • Comparative Study
  • Validation Study

MeSH terms

  • Adenoma / blood
  • Adenoma / diagnosis
  • Adenoma / metabolism
  • Adenoma / urine
  • Aged
  • Biomarkers / blood
  • Biomarkers / urine*
  • Case-Control Studies
  • Colonic Neoplasms / blood
  • Colonic Neoplasms / diagnosis
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / urine
  • Diet, Healthy*
  • Dietary Supplements
  • Early Detection of Cancer
  • Feeding Behavior*
  • Female
  • Hospitals, Military
  • Humans
  • Machine Learning
  • Male
  • Maryland
  • Metabolomics / methods
  • Middle Aged
  • Models, Biological*
  • Nutrition Assessment*
  • Patient Compliance*
  • Regression Analysis
  • Self Report


  • Biomarkers