Research progress on the metabolic fate of citrus flavonoids and strategies to improve bioavailability

Abstract

Citrus flavonoids have various health-promoting effects, such as antioxidant, anti-inflammatory, and metabolic regulatory activities, whereas their low oral bioavailability greatly impairs their in vivo efficacy. Substitution patterns of hydroxyl, methoxyl, and glycosyl groups determine their metabolic fate. As a narrative review, this paper follows the thread of “structure-metabolism-efficacy” and reviews literature covering metabolism, gut microbiota, delivery systems, structural modifications, in vivo bioactivity, and clinical studies. Molecular-structure-based comparisons of bioavailability-enhancement strategies are made. Most bioactivity findings are derived from cellular and animal studies, while human pharmacokinetic and clinical data remain scarce. Prospects, including AI-assisted formulation, personalized nutrition, and high-value utilization of citrus by-products, are discussed, aiming to provide an in-depth theoretical reference for the development of citrus-flavonoid-based functional products.