Hyaluronic acid in functional foods and oral supplements: linking molecular weight, bioavailability, and food matrix effects to clinical translation.

Hyaluronic acid (HA) has attracted growing interest as a multifunctional ingredient in functional foods and oral supplements because of its techno-functional properties and proposed benefits for skin and joint health. However, the physiological relevance of orally administered HA remains difficult to interpret because its gastrointestinal fate, exposure, and clinical outcomes may depend on molecular weight distribution, dose, formulation, processing history, food-matrix interactions, and host-related factors. This review integrates evidence on HA molecular characteristics, gastrointestinal transformation, food applications, and clinical translation. Current evidence indicates low overall oral bioavailability and suggests that very small HA-derived oligosaccharides are more plausible candidates for epithelial passage, whereas larger polymers generally require further gastrointestinal degradation. These tendencies do not establish a universal molecular-weight hierarchy for systemic exposure, local activity, or clinical efficacy. In food systems, HA has been investigated in dairy products, protein gels, emulsions, edible films, coatings, and delivery systems, but most evidence remains based on model or in vitro studies, with limited characterization of HA after processing and digestion. Clinical studies have reported improvements in selected skin hydration, wrinkle-related, and joint discomfort outcomes; nevertheless, interpretation is constrained by incomplete molecular characterization, heterogeneous doses and formulations, short intervention periods, and frequent use of multi-ingredient products, which prevent HA-specific attribution. Overall, HA has potential as a techno-functional food ingredient and oral supplement, but progress requires standardized molecular reporting, adequately controlled HA-only trials, and matrix-specific studies linking processing, gastrointestinal fate, exposure, and clinically relevant outcomes.