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: Intraindividual variability of SREM was assessed in seven young subjects, after consuming 10.7 mg CF/kg body weight (BW) on two occasions separated by 1 week. The effect of age on flavanols ADME was assessed in 20 young (18-35 years) and 20 elderly (65-80 years) 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 three days separated by 1 week of wash-out. Blood and urine samples were collected for 24-h post consumption. The intraindividual variation, measured as CV(%) with respect to the area-under-the-curve of the concentration over time (AUC(0-6h) ) of SREM, was 16%, while the interindividual 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 metabolites were lower in the elderly. CONCLUSION: Cocoa flavanols are absorbed, metabolized, and excreted in healthy young and elderly subjects with relatively small differences between the two groups.
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: Intraindividual variability of SREM was assessed in seven young subjects, after consuming 10.7 mg CF/kg body weight (BW) on two occasions separated by 1 week. The effect of age on flavanols ADME was assessed in 20 young (18-35 years) and 20 elderly (65-80 years) 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 three days separated by 1 week of wash-out. Blood and urine samples were collected for 24-h post consumption. The intraindividual variation, measured as CV(%) with respect to the area-under-the-curve of the concentration over time (AUC(0-6h) ) of SREM, was 16%, while the interindividual 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 metabolites were lower in the elderly. CONCLUSION: Cocoa flavanols are absorbed, metabolized, and excreted in healthy young and elderly subjects with relatively small differences between the two groups.
Authors: Dragan Milenkovic; Christine Morand; Aedin Cassidy; Aleksandra Konic-Ristic; Francisco Tomás-Barberán; José M Ordovas; Paul Kroon; Raffaele De Caterina; Ana Rodriguez-Mateos Journal: Adv Nutr Date: 2017-07-14 Impact factor: 8.701
Authors: Charlotte C J R Michielsen; Enrique Almanza-Aguilera; Elske M Brouwer-Brolsma; Mireia Urpi-Sarda; Lydia A Afman Journal: Genes Nutr Date: 2018-07-27 Impact factor: 5.523
Authors: Javier I Ottaviani; Redmond Fong; Jennifer Kimball; Jodi L Ensunsa; Abigail Britten; Debora Lucarelli; Robert Luben; Philip B Grace; Deborah H Mawson; Amy Tym; Antonia Wierzbicki; Kay-Tee Khaw; Hagen Schroeter; Gunter G C Kuhnle Journal: Sci Rep Date: 2018-06-29 Impact factor: 4.379
Authors: Claudine Manach; Dragan Milenkovic; Tom Van de Wiele; Ana Rodriguez-Mateos; Baukje de Roos; Maria Teresa Garcia-Conesa; Rikard Landberg; Eileen R Gibney; Marina Heinonen; Francisco Tomás-Barberán; Christine Morand Journal: Mol Nutr Food Res Date: 2016-11-15 Impact factor: 5.914