Plasma metabolites associated with a protein-rich dietary pattern: Results from the OmniHeart trial

Authors: KIM, HYUNJU - Johns Hopkins University; LICHTENSTEIN, ALICE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WHITE, KAREN - Johns Hopkins University; WONG, KARI - Metabolon, Inc; MILLER III, EDGAR - Johns Hopkins University; CORESH, JOSEF - Johns Hopkins University; APPEL, LAWRENCE - Johns Hopkins University; REBHOLZ, CASEY - Johns Hopkins University

Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/22/2022
Publication Date: 1/26/2022
Citation: Kim, H., Lichtenstein, A.H., White, K., Wong, K.E., Miller III, E.R., Coresh, J., Appel, L.J., Rebholz, C.M. 2022. Plasma metabolites associated with a protein-rich dietary pattern: Results from the OmniHeart trial. Molecular Nutrition and Food Research. https://doi.org/10.1002/mnfr.202100890.
DOI: https://doi.org/10.1002/mnfr.202100890

Interpretive Summary: Whether the intake of protein relative to carbohydrate is associated with chronic disease risk has yet to be determined. A major difficulty in answering this question is related to our inability to accurately measure the amount and type of dietary protein consumed. One promising approach to solve this problem is the identify biomarkers of protein intake, that is plasma molecules that increase or decrease on the basis of how much or what type of protein is consumed. To accomplish this we used samples from the OmniHeart trial. During the trial dietary patterns with different amounts and types of protein were fed to participants for 6 weeks each. Identified were 102 metabolites that differed after the participants consumed protein-rich and carbohydrate-rich (low protein) dietary patterns. These metabolites fell into the categories of lipids (n=35), amino acids (n=27), and xenobiotics (n=24; metabolites not found in animal sources of protein). The metabolites which were the most different between the protein-rich and carbohydrate-rich dietary patterns were related to plant protein intake, food or beverage intake, and preparation methods. These data indicate some metabolites may be objective biomarkers for protein-rich dietary patterns.

Technical Abstract: Scope Lack of biomarkers is a challenge for the accurate assessment of protein intake and interpretation of observational study data. The study aims to identify biomarkers of a protein-rich dietary pattern. Methods and Results The Optimal Macronutrient Intake Trial to Prevent Heart Disease (OmniHeart) trial is a randomized cross-over feeding study which tested three dietary patterns with varied macronutrient content (carbohydrate-rich; protein-rich with about half from plant sources; and unsaturated fat-rich). In 156 adults, differences in log-transformed plasma metabolite levels at the end of the protein- and carbohydrate-rich diet periods using paired t-tests is examined. Partial least-squares discriminant analysis is used to identify a set of metabolites which are influential in discriminating between the protein-rich versus carbohydrate-rich dietary patterns. Of 839 known metabolites, 102 metabolites differ significantly between the protein-rich and the carbohydrate-rich dietary patterns after Bonferroni correction, the majority of which are lipids (n = 35), amino acids (n = 27), and xenobiotics (n = 24). Metabolites which are the most influential in discriminating between the protein-rich and the carbohydrate-rich dietary patterns represent plant protein intake, food or beverage intake, and preparation methods. Conclusions The study identifies many plasma metabolites associated with the protein-rich dietary pattern. If replicated, these metabolites may be used to assess level of adherence to a similar dietary pattern.