PROJECT SUMMARY Dietary indices and scores provide a comprehensive and robust approach for nutritional exposure assessment, especially in relation to chronic disease risk. While dietary supplement (DS) use is very common among the U.S. population, with over 52% of adults and 33% of children routinely taking one or more (predominantly nutrient containing) products, no existing metrics assessed intakes from DS in addition to those from the diet. For this reason, we developed the Total Nutrient Index (TNI), a measure designed to evaluate total usual micronutrient intakes, inclusive of intakes from foods and DS, relative to the Dietary Reference Intakes for eight micronutrients identified as under consumed among the U.S. population by the 2015-2020 Dietary Guidelines for Americans (DGA) in the first period of this award. We examined the relative validity of the TNI compared to biomarkers of nutritional status among a nationally representative sample of U.S. adults and determined that 1) the TNI is a useful metric for total micronutrient exposure assessment, and 2) that the TNI yielded higher correlations with nutritional biomarkers when compared with those obtained from dietary intake alone. However, with the emergence of the precision nutrition era, understanding how unique combinations of nutrients and specific amounts of these nutrients can optimize the nutritional and health status of different population subgroups is of utmost importance. Accordingly, in the present competing continuation proposal, we intend to update the TNI to accommodate a life stage approach, to utilize machine learning techniques to identify critical nutrients and in what combinations optimally benefit the health and nutrition of individuals across the life course, and relate the TNI to risk factors, health outcomes, and mortality. In Aim 1, we plan to develop and validate the TNI-2, an updated extension of the TNI that is tailored to different life stages and includes nutrients and food components of