How does the flavan-3-ol structure condition the quali-quantitative production of phenolic metabolites? Insights from a 3-arm intervention

The structural properties of parent flavan-3-ols may affect their metabolism, with a putative impact on biological response. This study aims to evaluate the influence of the chemical structure on the metabolism and urinary excretion of flavan-3-ol metabolites. An acute intervention trial was performed in 11 subjects consuming flavan-3-ols from different sources: green tea extract (GT), grape seed extract with a high monomer content (GSM), and grape seed extract rich in procyanidins (GSP). Flavan-3-ols from GT had the highest bioavailability, while flavan-3-ols from GSP were the lowest. GT was characterized by trihydroxylated and 3',5'-dihydroxylated derivatives, GSM was characterized by (epi)catechins, phenyl-γ-valerolactones, phenylvaleric acids, phenylpropanoic acids, and 1,2-dihydroxybenzenes, while GSP urine contained predominantly low-molecular-weight metabolites. Moreover, the endogenous production of phenolic metabolites was evaluated, suggesting that small phenolics may determine biases in the bioavailability estimates. This work demonstrates how the flavan-3-ol structure influences the bioavailability of this (poly)phenol class, being key in investigating the health effects derived from the intake of flavan-3-ol-rich foods.