A metabolite index of ultra-processed food intake is associated with stroke, cancer mortality, and all-cause mortality

Ultra-processed foods (UPFs) are associated with adverse health outcomes, but measurement of UPF intake in epidemiological studies remains challenging. Dietary assessments typically employ recall questionnaires, which may lead to measurement errors and misclassifications. Here, we develop a plasma metabolite index of UPF consumption to objectively measure UPF intake. Using two years of authentic food purchasing records from the ChooseWell 365 cohort, we identify metabolites associated with long-term UPF intake. We then apply the UPF-metabolite index to the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, a population-based cohort of U.S. adults followed for incident health outcomes. The UPF-metabolite index was associated with leading causes of morbidity and mortality, including incident stroke, all-cause mortality, and cancer mortality. Mediation analysis revealed that the UPF-metabolite index accounts for 62% of the association between UPF intake and stroke risk. These findings suggest that the UPF-metabolite index offers an objective method for assessing UPF intake and its contribution to diet-related disease risk.