A Systematic Review and Comprehensive Evaluation of Human Intervention Studies to Unravel the Bioavailability of Hydroxycinnamic Acids
Reviewartikel, 2024

Significance: Hydroxycinnamic acids (HCAs) are the main phenolic acids in the western diet. Harmonizing the available information on the absorption, distribution, metabolism, and excretion (ADME) of HCAs is fundamental to unraveling the compounds responsible for their health effects. This work systematically assessed pharmacokinetics, including urinary recovery, and bioavailability of HCAs and their metabolites, based on literature reports.Recent Advances: Forty-seven intervention studies with coffee, berries, herbs, cereals, tomato, orange, grape products, and pure compounds, as well as other sources yielding HCA metabolites, were included. Up to 105 HCA metabolites were collected, mainly acyl-quinic and C-6-C-3 cinnamic acids. C-6-C-3 cinnamic acids, such as caffeic and ferulic acid, reached the highest blood concentrations (maximum plasma concentration [C-max] = 423 nM), with time to reach C-max (T-max) values ranging from 2.7 to 4.2 h. These compounds were excreted in urine in higher amounts than their phenylpropanoic acid derivatives (4% and 1% of intake, respectively), but both in a lower percentage than hydroxybenzene catabolites (11%). Data accounted for 16 and 18 main urinary and blood HCA metabolites, which were moderately bioavailable in humans (collectively 25%).Critical Issues: A relevant variability emerged. It was not possible to unequivocally assess the bioavailability of HCAs from each ingested source, and data from some plant based-foods were absent or inconsistent.Future Directions: A comprehensive study investigating the ADME of HCAs derived from their most important dietary sources is urgently required. Eight key metabolites were identified and reached interesting plasma C-max concentrations and urinary recoveries, opening up new perspectives to evaluate their bioactivity at physiological concentrations.



caffeoylquinic acids


chlorogenic acids




Giuseppe Di Pede

Universita degli Studi di Parma

Pedro Mena

Universita degli Studi di Parma

Letizia Bresciani

Universita degli Studi di Parma

Mariem Achour

Université Clermont Auvergne

Rosa M. Lamuela-Raventós

Instituto de Salud Carlos III

Universitat de Barcelona

Ramon Estruch

Universitat de Barcelona

Instituto de Salud Carlos III

Rikard Landberg

Chalmers, Life sciences, Livsmedelsvetenskap

Sabine E. Kulling

Max Rubner-Institut, Germany

David Wishart

University of Alberta

Ana Rodriguez-Mateos

King's College London

Michael N. Clifford

University of Surrey

Monash University

Alan Crozier

King Saud University

University of Glasgow

Claudine Manach

Université Clermont Auvergne

Daniele Del Rio

Universita degli Studi di Parma

Antioxidants and Redox Signaling

1523-0864 (ISSN) 15577716 (eISSN)

Vol. 40 7-9 510-541







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