Revisiting the bioavailability of flavan-3-ols in humans: A systematic review and comprehensive data analysis
Review article, 2023

This 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.








Giuseppe Di Pede

University of Parma

Pedro Mena

University of Parma

Letizia Bresciani

University of Parma

Mariem Achour

Clermont Auvergne University

Rosa M. Lamuela-Raventós

University of Barcelona

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

Ramon Estruch

University of Barcelona

Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición

Rikard Landberg

Chalmers, Life Sciences, Food and Nutrition Science

Sabine E. Kulling

Max Rubner-Institut, Germany

David S. Wishart

University of Alberta

Ana Rodriguez-Mateos

King's College London

Alan Crozier

King Saud University

School of Medicine, Dentistry & Nursing

Claudine Manach

Clermont Auvergne University

Daniele Del Rio

University of Parma

Molecular Aspects of Medicine

0098-2997 (ISSN) 18729452 (eISSN)

Vol. 89 101146

Food phytochemicals matter for cardiometabolic health

Formas (2019-02201), 2019-12-01 -- 2022-12-31.

Subject Categories

Pharmaceutical Sciences

Food Science

Nutrition and Dietetics





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