Nian Liu, Yang Yan, Xinggang Ni, Rong Liu, Liufeng Zheng, Bing Zhang, Zeyuan Deng, Jing Li
Fat-soluble vitamins (FSVs), including vitamins A, D, E, and K, are essential micronutrients but exhibit poor water solubility, high sensitivity to light, heat, and oxidation, and consequently low bioavailability, which limits their effective utilization in functional food and nutraceutical systems. Recent advances show that binding or encapsulation of FSVs with food macromolecules-proteins, lipids, and carbohydrates-can markedly improve their physicochemical stability and gastrointestinal absorption. This review critically summarizes the molecular mechanisms underlying these interactions and explains how they alter the structural organization and delivery performance of FSVs. The major characterization techniques, including FTIR, fluorescence spectroscopy, NMR, calorimetry, and light-scattering analyses, are discussed to illustrate how they reveal binding modes and guide carrier design. Comparative analysis highlights that proteins provide specific hydrophobic pockets and hydrogen-bonding sites, lipids enable micellar solubilization and membrane transport, and carbohydrates such as cyclodextrins or polysaccharide matrices contribute to inclusion, protection, and controlled release. Collectively, these macromolecule-based strategies offer promising approaches to enhance the stability and bioavailability of FSVs in food and pharmaceutical formulations. Future directions include the development of environmentally responsive carriers, the investigation of microbiota-mediated metabolism of bound FSVs, and the integration of artificial intelligence-assisted design to accelerate the creation of intelligent and personalized vitamin delivery systems.