Plasma Metabolites Associated with a Protein-Rich Dietary Pattern: Results from the OmniHeart Trial

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.