Circulating metabolites and fatty acids associated with ultra-processed food consumption: results from the EPIC study

Emerging evidence links consumption of ultra-processed foods (UPF) to higher risks of non-communicable diseases and mortality, but the underlying mechanisms remain unclear. This study aimed to identify molecular signatures of UPF intake in participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Foods were classified into four groups using the Nova system, including UPF. The analysis included 6,177 participants with data on 129 endogenous metabolites and 9,029 with data on 37 plasma fatty acids (FAs) from EPIC nested case-control studies. Concentrations were normalized across batches and centers. UPF intake (grams/day) was linked to metabolite and FA profiles using linear and LASSO regression models, adjusted for demographic, lifestyle, and dietary factors. UPF intake was associated with 22 circulating metabolites and eight plasma FAs. Most metabolite associations were inverse, particularly for compounds involved in energy (e.g., asparagine) and lipid metabolism (e.g., propionyl carnitine, glycerophospholipids, and sphingomyelins). FA profiles showed positive associations with industrial trans fats (e.g., elaidic acid), long-chain saturated FAs (e.g., stearic acid), and n-6 polyunsaturated FAs (e.g., dihomo-γ-linolenic acid). UPF consumption is associated with distinct metabolic and fatty acid profiles, providing insights into potential biological pathways linking UPF to adverse health outcomes.