Project Summary/Abstract The Dietary Reference Intakes (DRIs) for iron were first established in 2001, drawing upon the best available data at that time. However, the committee was limited by the scarcity of studies, with data dating back to the 1950s and involving a relatively small number of subjects from homogenous populations outside the US. Consequently, the existing DRIs for iron may not accurately reflect the needs of the increasingly diverse US population. This proposed supplemental study to the Nutrition for Precision Health (NPH) trial powered by the All of Us Research Program will determine dietary iron requirements in a representative sample of US adults. The proposed study will recruit a large number of participants (n=~300) enrolled in NPH and collect data used to determine iron requirements. Specific Aim 1 will quantify iron losses and Specific Aim 2 will determine iron bioavailability from 3 different mixed diets typically consumed in the US. Factors affecting iron loss and iron bioavailability will be explored. Indicators of iron status will also be added to the NPH protocol. These data will serve as a crucial resource for informing the necessary updates to the current DRIs for iron, ensuring they accurately reflect the specific needs of the US population. This study would not be possible without the larger parent study, as it relies on the infrastructure, resources, and diverse participants recruited for the NPH trial. Data will be integrated with the All of Us database to facilitate future discoveries that may inform public health recommendations and strategies for preventing iron-related health conditions.