Physiologically relevant gastrointestinal digestion models for infants, adults, and the elderly are commonly used to explore the fate of food in vitro. However, no consensus protocol exists to simulate the specific conditions observed in the stomach of people using oral proton pump inhibitors (PPIs), a class of widely prescribed medications that reduce gastric acid secretion and may alter food digestion and nutrient absorption. The first objective of this study was to propose an in vitro gastric digestion protocol adapted to model PPI use. This protocol is an extension of the semi-dynamic INFOGEST protocol previously developed to mimic the digestion of an adult human (referred to hereinafter as "Standard"), with two modifications based on reported clinical effects of PPIs: (i) a final gastric pH of 4.2 and (ii) a 50 % reduction in simulated gastric acid fluid volume. The second objective was to compare the release kinetics of peptides, soluble carbohydrates, lipids, and minerals during simulated gastric digestion of a mixed meal (bread, cheese, and tomato) with both standard and PPI versions of the protocol. Results demonstrated that the release of peptides, arabinose, and minerals, including calcium, magnesium, and phosphorus, was significantly (p <
0.05) reduced in the PPI model, while the hydrolyses of starch and lipids, assessed through maltose release and triacylglycerol disappearance, respectively, were not significantly affected. These findings are in agreement with the expected effects of reduced gastric acidity on pepsin activity and mineral solubility. These findings are also consistent with known or presumed side effects of PPIs such as an increased risk of hypomagnesemia, fractures, skeletal muscle loss, and vitamin B