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

Giuseppe Di Pede; Pedro Mena; Letizia Bresciani; Mariem Achour; Rosa M Lamuela-Raventós; Ramon Estruch; Rikard Landberg; Sabine E Kulling; David Wishart; Ana Rodriguez-Mateos; Alan Crozier; Claudine Manach; Daniele Del Rio

doi:10.1016/j.mam.2022.101146

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

Mol Aspects Med. 2023 Feb:89:101146. doi: 10.1016/j.mam.2022.101146. Epub 2022 Oct 4.

Authors

Affiliations

¹ Department of Food and Drugs, University of Parma, Parma, Italy.
² Department of Food and Drugs, University of Parma, Parma, Italy; Microbiome Research Hub, University of Parma, 43124, Parma, Italy. Electronic address: pedro.mena@unipr.it.
³ Université Clermont Auvergne, INRAE, Human Nutrition Unit, Clermont-Ferrand, France.
⁴ Department of Nutrition, Food Sciences and Gastronomy, XaRTA, School of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; INSA-UB, Nutrition and Food Safety Research Institute, University of Barcelona, 08921, Santa Coloma de Gramanet, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029, Madrid, Spain.
⁵ CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029, Madrid, Spain; Department of Internal Medicine, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), University of Barcelona, 08036, Barcelona, Spain.
⁶ Department of Biology and Biological Engineering, Division of Food and Nutrition Science, Chalmers University of Technology, Gothenburg, Sweden.
⁷ Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Department of Safety and Quality of Fruit and Vegetables, Haid-und-Neu-Str. 9, 76131, Karlsruhe, Germany.
⁸ Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada; Department of Computing Science, University of Alberta, Edmonton, AB T6G 2E8, Canada.
⁹ Department of Nutritional Sciences, School of Life Course and Population Sciences, King's College London, SE1 9NH, London, United Kingdom.
¹⁰ Department of Chemistry, King Saud University, Riyadh, Saudi Arabia; School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, G12 8QQ, UK.
¹¹ Department of Food and Drugs, University of Parma, Parma, Italy; Microbiome Research Hub, University of Parma, 43124, Parma, Italy.

PMID: 36207170
DOI: 10.1016/j.mam.2022.101146

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 (C_max) of 260 and 88 nmol/L at 1.8 and 5.3 h (T_max) 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.

Keywords: (Poly)phenols; Excretion; Metabolites; Pharmacokinetics; Phenolics; Phenyl-γ-valerolactones.

Publication types

Systematic Review
Review
Research Support, Non-U.S. Gov't

MeSH terms

Biological Availability
Catechin* / metabolism
Diet
Humans
Proanthocyanidins*

Substances

Catechin
Proanthocyanidins