Dietary glycated peptides from UHT Milk reach the human circulatory system

Ultra-high-temperature (UHT) processing profoundly alters milk protein structure, generating modified peptides with uncertain biological effects. This study combined in vitro gastrointestinal digestion (INFOGEST protocol, with or without brush border membrane enzymes) and untargeted peptidomics to demonstrate that UHT-derived peptides, including lactosylated, hexosylated, oxidized, deamidated, and other Maillard-related adducts, can resist complete hydrolysis under simulated conditions and remain detectable after digestion. Parallel plasma analysis from six volunteers consuming UHT milk confirmed the presence of numerous modified peptides, many bearing multiple post-translational modifications and longer sequences than those generated in vitro, suggesting ongoing peptide transformation in vivo. Cross-linked adducts, typical associated with severe heating, were not detected in plasma. Overall, these findings provide direct molecular evidence in humans that UHT milk consumption leads to transient systemic exposure to chemically modified peptides, emphasizing the nutritional and physiological relevance of heat-induced protein modifications in processed foods.