Metabolic Phenotyping to Assess Personalized Nutrition: Use of the Response-to-Challenge Model

Public health is seeking to personalize diets for individual metabolic needs, yet challenges must be addressed. Personalizing diets will require a molecular, mechanistic and quantitative understanding of individual responses to food. Compositionally defined diets fed to subjects in a crossover, post-prandial design to interrogate 1) fatty acid metabolism and 2) plasma lipoproteins. The elongation of 18:3n6 was assessed by appearance of its products in plasma at 2 hr intervals. Using the same design, a challenge rich in saturated fat was compared with unsaturated oil by measuring composition and size of post-prandial lipoproteins. Plasma fatty acids were quantified by gas chromatography and lipoprotein size and proteome were measured by NMR and LC-MS/MS. Individual responses were consistent yet there were significant differences among subjects in key aspects of lipid metabolism. Notably elongation of 18:3n6 stratified individuals into responders and non-responders, even though if analyzed as a group, elongation was not significant. Segregation of the subjects into responders and non-responders, was again seen in the plasma lipoprotein distribution. Saturated fat consumption in a subset of subjects, decreased VLDL size, yet analyzed as a group mean, the effect disappeared. Foods designed to probe metabolic pathways reveal critical differences in the nutritional phenotype among individuals.