SCOPE:

An understanding of the pharmacokinetics of structurally related (-)-epicatechin metabolites (SREM) is a prerequisite for considering cocoa flavanols (CF) in the context of dietary recommendations. The objective of this study was to compare the absorption, metabolism, and excretion of SREM in healthy young and elderly Caucasian men.

METHODS AND RESULTS:

Intra-individual variability of SREM was assessed in 7 young subjects, after consuming 10.7 mg CF/kg body weight (BW) on two occasions separated by one week. The effect of age on flavanols ADME was assessed in 20 young (18-35y) and 20 elderly (65-80y) healthy male subjects receiving 5.3 and 10.7 mg total CF/kg BW or 1 g of acetaminophen as a control to compare differences in Phase II metabolism on 3 days separated by 1 week of wash-out. Blood and urine samples were collected for 24 h post consumption. The intra-individual variation, measured as CV(%) with respect to the area-under-the-curve of the concentration over time (AUC(0-6h) ) of SREM, was 16%, whilst the inter-individual variation in AUC(0-6h) , was 38%, comparable to acetaminophen (39%). The AUC(0-6h) and the 24 h excretion of total SREM was not significantly different between young and elderly subjects. At the high intake amount, the AUC(0-6h) of (-)-epicatechin-3'-β-D-glucuronide was greater in elderly subjects, whereas the AUC(0-6h) of 3'-O-methyl-(-)-epicatechin-5-sulfate and 3'-O-methyl-(-)-epicatechin-7-sulfate as well as the 24 h urinary excretion of γ-valerolactone (γ-VL) metabolites were lower in the elderly.

 

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