TY - JOUR
T1 - Revisiting the bioavailability of flavan-3-ols in humans
T2 - A systematic review and comprehensive data analysis
AU - Di Pede, Giuseppe
AU - Mena, Pedro
AU - Bresciani, Letizia
AU - Achour, Mariem
AU - Lamuela-Raventós, Rosa M
AU - Estruch, Ramon
AU - Landberg, Rikard
AU - Kulling, Sabine E
AU - Wishart, David
AU - Rodriguez-Mateos, Ana
AU - Crozier, Alan
AU - Manach, Claudine
AU - Del Rio, Daniele
N1 - Funding 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 .
Publisher Copyright:
© 2022
PY - 2022/10/4
Y1 - 2022/10/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85140261638&partnerID=8YFLogxK
U2 - 10.1016/j.mam.2022.101146
DO - 10.1016/j.mam.2022.101146
M3 - Review article
C2 - 36207170
SN - 0098-2997
SP - 101146
JO - Molecular Aspects of Medicine
JF - Molecular Aspects of Medicine
M1 - 101146
ER -