Evaluation of potential metabolomic-based biomarkers of protein, carbohydrate and fat intakes using a controlled feeding study

Eur J Nutr. 2021 Dec;60(8):4207-4218. doi: 10.1007/s00394-021-02577-1. Epub 2021 May 15.

Abstract

Purpose: Objective biomarkers of dietary exposure are needed to establish reliable diet-disease associations. Unfortunately, robust biomarkers of macronutrient intakes are scarce. We aimed to assess the utility of serum, 24-h urine and spot urine high-dimensional metabolites for the development of biomarkers of daily intake of total energy, protein, carbohydrate and fat, and the percent of energy from these macronutrients (%E).

Methods: A 2-week controlled feeding study mimicking the participants' habitual diets was conducted among 153 postmenopausal women from the Women's Health Initiative (WHI). Fasting serum metabolomic profiles were analyzed using a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for aqueous metabolites and a direct-injection-based quantitative lipidomics platform. Urinary metabolites were analyzed using 1H nuclear magnetic resonance (NMR) spectroscopy at 800 MHz and by untargeted gas chromatography-mass spectrometry (GC-MS). Variable selection was performed to build prediction models for each dietary variable.

Results: The highest cross-validated multiple correlation coefficients (CV-R2) for protein intake (%E) and carbohydrate intake (%E) using metabolites only were 36.3 and 37.1%, respectively. With the addition of established dietary biomarkers (doubly labeled water for energy and urinary nitrogen for protein), the CV-R2 reached 55.5% for energy (kcal/d), 52.0 and 45.0% for protein (g/d, %E), 55.9 and 37.0% for carbohydrate (g/d, %E).

Conclusion: Selected panels of serum and urine metabolites, without the inclusion of doubly labeled water and urinary nitrogen biomarkers, give a reliable and robust prediction of daily intake of energy from protein and carbohydrate.

Keywords: Carbohydrate; Controlled feeding study; Dietary biomarker; Metabolomics; Postmenopausal women; Protein.

MeSH terms

  • Biomarkers
  • Carbohydrates
  • Chromatography, Liquid
  • Diet
  • Female
  • Humans
  • Metabolomics*
  • Tandem Mass Spectrometry*

Substances

  • Biomarkers
  • Carbohydrates