Revisiting the bioavailability of flavan-3-ols in humans: A systematic review and comprehensive data analysis. (February 2023)

• Record Type: Journal Article
• Authors: Di Pede, Giuseppe; Mena, Pedro; Bresciani, Letizia; Achour, Mariem; Lamuela-Raventós, Rosa M.; Estruch, Ramon; Landberg, Rikard; Kulling, Sabine E.; Wishart, David; Rodriguez-Mateos, Ana; Crozier, Alan; Manach, Claudine; Del Rio, Daniele
• Is Part Of: Molecular aspects of medicine. Volume 89(2023)
• Publication Date: 2023-02
• Subjects: (Poly)phenols -- Phenolics -- Phenyl-γ-valerolactones -- Pharmacokinetics -- Metabolites -- Excretion; Pathology, Molecular -- Periodicals; Medicine -- Periodicals; Biochemistry -- Periodicals; Medicine -- Periodicals; Molecular Biology -- Periodicals; Pathologie moléculaire -- Périodiques; Médecine -- Périodiques; Electronic journals; 612.015
• DOI: 10.1016/j.mam.2022.101146
• Languages: English
• ISSNs: 0098-2997

Abstract

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. Graphical abstract: Image 1 Highlights: Understanding flavan-3-ol bioavailability is essential to unravel their benefits. Pharmacokinetic profiles of 180 flavan-3-ol metabolites were assessed. Concentration levels for main metabolites of flavan-3-ols ranged 67–860 nmol/L. Mean bioavailability for dietary flavan-3-ols is 31%. Intra- and inter-source differences in flavan-3-ol bioavailability emerged.