Revisiting the bioavailability of flavan-3-ols in humans: a systematic review and comprehensive data analysis

Di Pede, G. et al. (2023) Revisiting the bioavailability of flavan-3-ols in humans: a systematic review and comprehensive data analysis. Molecular Aspects of Medicine, 89, 101146. (doi: 10.1016/j.mam.2022.101146) (PMID:36207170)

Abstract

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.

• Item Type: Articles
• Additional Information: This work has received funding from the French Agency of National Research (ANR, grant 19-HDH2-0002-01), the Ministero delle Politiche Agricole Alimentari e Forestali (MIPAAF, ID 1160), the Spanish Ministry of Science, Innovation, and Universities (AC19/00100), the German Federal Ministry of Food and Agriculture (BMEL) through the Federal Office for Agriculture and Food (BLE) (2819ERA11F), and the Swedish Research Council for Sustainable Development as part of the FoodPhyt project, under the umbrella of the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL) (2019–02201) and of the ERA-NET Cofund HDHL INTIMIC (GA N° 727565 of the EU Horizon 2020 Research and Innovation Programme). A.C. was supported by the Distinguished Scientist Fellowship Program (DSFP) at King Saud University, Riyadh, Saudi Arabia.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Crozier, Professor Alan
• Authors: Di Pede, G., Mena, P., Bresciani, L., Achour, M., Lamuela-Raventós, R. M., Estruch, R., Landberg, R., Kulling, S. E., Wishart, D., Rodriguez-Mateos, A., Crozier, A., Manach, C., and Del Rio, D.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Molecular Aspects of Medicine
• Publisher: Elsevier
• ISSN: 0098-2997
• ISSN (Online): 1872-9452
• Published Online: 04 October 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Molecular Aspects of Medicine 89:101146
• Publisher Policy: Reproduced under a Creative Commons License