ABSTRACT
The reasons for individual variability in the physiologic response to dietary patterns are not well understood but
hamper efforts to provide optimum diets to our population. There is an urgent need to understand the complex
interaction of demographic, genetic, metabolic, behavioral, psychosocial, and environmental factors that affect
the responses to dietary patterns in order to prevent and treat nutrition-related chronic diseases. The field of
“precision nutrition” holds great promise for elucidating these interactions to eventually predict the optimal diet
for an individual or groups of individuals. The overall objective of this application is to demonstrate that the
University of Alabama at Birmingham (UAB) is uniquely positioned to join the consortium as a Nutrition for
Precision Health Clinical Center (RFA-RM-21-005). The study team will collect a wide range of physiological and
metabolic data from individuals in response to free-living (module 1) and controlled diets (modules 2 & 3), that
will be used in analyses to determine potential predictors of response to diet. Sophisticated data methods
(artificial intelligence, machine learning, mathematical modelling) will then be employed by the study group to
identify the comprehensive phenotypes needed for individualizing diet prescriptions. We aim to accomplish the
following three specific aims: Specific Aim 1 (module 1): Conduct an observational study of 2000 free-living
individuals consuming their usual diet for 14 days. The physiologic responses to a standardized test meal
challenge will be assessed while they are consuming their usual diet. Specific Aim 2 (module 2): Conduct a
free-living controlled feeding study in 400 subjects fed three isocaloric diets varying in macronutrient
composition at maintenance energy requirements. Diets are designed to elicit a wide range of responses
among participants. The physiologic responses to standardized test meals and diet-specific meals will be
measured at the end of each 14-day diet period. We will also collect measures of 24-hr glucose, 24-hr blood
pressure, 24-hr physical activity, cardiorespiratory fitness, and sleep during each diet period. Specific Aim 3
(module 3): Conduct a domiciled controlled feeding study in 150 subjects of three isocaloric diets (same
diets as in aim #1) fed at maintenance energy requirements. In addition to module 2 outcomes, assessments
including room calorimetry, doubly labelled water, cardiorespiratory fitness, and muscle and fat biopsies will be
completed in module 3 participants while they are domiciled in cottages at the Lakeshore Foundation Campus
near UAB. Achieving these aims will create a database that allows sophisticated data analysis (e.g., AI, machine
learning) to develop algorithms to match people to optimum diets. UAB, with access to >16,000 All of Us
participants in Birmingham, outstanding facilities for conducting diet interventions, and an outstanding
research team, can be a valued member of the Nutrition for Precision Health Consortium.