Because of the widely acknowledged impact of food consumption on health, better mechanistic insights into the behaviour of foods along the digestive tract are required. A wide range of in vitro digestion (IVD) methods have been developed and used to gain insights into these processes, as well as the bio accessibility and bioavailability of food components. The way these methods simulate the complex, transient, and dynamic nature of in vivo digestion varies greatly (Lucas-González et al., 2018). In vitro methods have the potential to provide specific, valuable scientific insights, and the appropriate protocol should be carefully chosen based on the purpose and research question. Rapid advances in digestion methods have aided in the understanding of the relationship between food processing, food structure, and nutrient digestion and release patterns. After all, the structural organisation of a food and its transformation throughout the gastrointestinal (GI) tract influence food digestion. Interestingly, a thorough understanding of structural transformations that occur throughout the food supply chain (food storage and processing) as well as during digestion could be used to create foods with improved digestive properties. Processing and product formulation can then be reverse engineered in this context to rationally design targeted food molecular, micro-, and macrostructures. (Food structural design, FSD) that results in specific digestive properties, i.e., food digestion design the in vivo human GI system and current state-of-the-art static and semi-dynamic IVD models are discussed. The current review then discusses critical strategic considerations for conducting IVD experiments. Recent reviews on IVD approaches have concentrated on a single macronutrient, food type, or population group, or have provided a descriptive overview of the current state of the art. However, an integrated overview of recent progress and evolution in food science and technology, specifically food structural design, remains lacking. IVD studies progress from endpoint to kinetic assessments. While endpoint evaluations are a simple approach, it is important to consider more than just the extent of macronutrient digestion. Digestive protocols based on kinetic approaches help to better understand the time-dependent evolution of macronutrient hydrolysis as well as structural changes in the digestive tract. In vitro food digestion research is increasingly shifting away from simplified models and toward more (semi-)dynamic models. While in vitro food digestion studies are always simplified, they should be conducted under physiologically relevant conditions to provide useful insights into the mechanisms of food digestion. Standardized, static methods are simple tools that are ideal for screening and (mechanistic) hypothesis development and testing. The easy-to-handle static procedures have special merit for investigating the effect of certain structuring efforts on digestion, particularly in the context of food digestion design. Digestion research is progressing from simplified food model systems to actual complex foods and meals. While studying simplified systems yields important mechanistic insights, real meals are complex and (multilevel) structured systems in which different co-ingested nutrients are heterogeneously distributed and may interact during digestion. The focus of research is shifting away from 'average healthy adults' and toward digestion methods tailored to the functioning of specific population groups, such as infants, the elderly, and people with GI disorders.

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