Review of factors affecting citrus polyphenol bioavailability and their importance in designing in vitro, animal, and intervention studies.

Evidence from in vitro, animal, and human studies links citrus fruit consumption with several health-promoting effects. However, many in vitro studies disregard bioavailability data, a key factor determining responses in humans. Citrus (poly)phenol metabolism and bioavailability follow specific pathways that vary widely among individuals and are affected by several intrinsic (age, sex, gut microbiota, metabolic state, genetic polymorphisms) and extrinsic (food matrix, co-consumed food, (poly)phenol solubility, dose, food processing, lifestyle) factors. The gut microbiota is crucial to both absorption of citrus (poly)phenols and the production of catabolites, and absorption of both takes place mostly in the colon. Citrus (poly)phenol absorption can reach up to 100% in some individuals when the sum of the gut microbiota products are taken into account. This review emphasizes the importance of understanding citrus (poly)phenol absorption, metabolism, and bioavailability using evidence primarily derived from human studies in designing in vitro, animal, and further human clinical studies.