Di Pede, GiuseppeMena, PedroBresciani, LetiziaAchour, MariemLamuela Raventós, Rosa Ma.Estruch Riba, RamonLandberg, RikardKulling, SabineWishart, David S.Rodríguez-Mateos, AnaCrozier, AlanManach, ClaudineDel Rio, Daniele2023-02-232023-02-232023-02-010098-2997https://hdl.handle.net/2445/194013This systematic review summarizes findings from human studies investigating the different routes of absorption, metabolism, distribution and excretion (ADME) of dietary flavan-3-ols and their circulating metabolites in healthy subjects. Literature searches were performed in PubMed, Scopus and the Web of Science. Human intervention studies using single and/or multiple intake of flavan-3-ols from food, extracts, and pure compounds were included. Forty-nine human intervention studies met inclusion criteria. Up to 180 metabolites were quantified from blood and urine samples following intake of flavan-3-ols, mainly as phase 2 conjugates of microbial catabolites (n =97), with phenyl-γ-valerolactones being the most representative ones (n =34). Phase 2 conjugates of monomers and phenyl-γ-valerolactones, the main compounds in both plasma and urine, reached two peak plasma concentrations (Cmax) of 260 and 88 nmol/L at 1.8 and 5.3 h (Tmax) after flavan-3-ol intake. They contributed to the bioavailability of flavan-3-ols for over 20%. Mean bioavailability for flavan-3-ols was moderate (31 ±23%, n bioavailability values =20), and it seems to be scarcely affected by the amount of ingested compounds. While intra- and inter-source differences in flavan-3-ol bioavailability emerged, mean flavan-3-ol bioavailability was 82% (n =1) and 63% (n =2) after ()-epicatechin and nut (hazelnuts, almonds) intake, respectively, followed by 25% after consumption of tea (n =7), cocoa (n =5), apples (n =3) and grape (n =2). This highlights the need to better clarify the metabolic yield with which monomer flavan-3-ols and proanthocyanidins are metabolized in humans. This work clarified in a comprehensive way for the first time the ADME of a (poly)phenol family, highlighting the pool of circulating compounds that might be determinants of the putative beneficial effects linked to flavan-3-ol intake. Lastly, methodological inputs for implementing well- designed human and experimental model studies were provided.application/pdfengcc-by-nc-nd (c) Giuseppe Di Pede, et al., 2023http://creativecommons.org/licenses/by-nc-nd/3.0/es/Compostos bioactiusFlavonoidesBioactive compoundsFlavonoidsinfo:eu-repo/semantics/article7299452023-02-23info:eu-repo/semantics/openAccess