title: Influence of age on the absorption, metabolism, and excretion of cocoa flavanols in healthy subjects.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Cocoa flavanols are absorbed, metabolized, and excreted in healthy young and elderly subjects with relatively small differences between the two groups.
authors.affiliation: Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK.|Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Rodriguez-Mateos
authors.affiliation: Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK.
authors.forename: Tania
authors.initials: T
authors.lastname: Cifuentes-Gomez
authors.affiliation: Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK.
authors.forename: Isidro
authors.initials: I
authors.lastname: Gonzalez-Salvador
authors.affiliation: Mars Inc, McLean, VA, USA.
authors.forename: Javier I
authors.initials: JI
authors.lastname: Ottaviani
authors.affiliation: Mars Inc, McLean, VA, USA.
authors.forename: Hagen
authors.initials: H
authors.lastname: Schroeter
authors.affiliation: Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.affiliation: Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.affiliation: Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK.
authors.forename: Jeremy P E
authors.initials: JP
authors.lastname: Spencer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001628:Beverages / Q000032:analysis*; D002099:Cacao / Q000737:chemistry*; D002392:Catechin / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D018592:Cross-Over Studies; D005419:Flavonoids / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000652:urine; D020719:Glucuronides / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D007783:Lactones / Q000737:chemistry / Q000378:metabolism / Q000652:urine*; D008297:Male; D008745:Methylation; D010352:Patient Dropouts; D065667:Renal Elimination; D013237:Stereoisomerism; D013463:Sulfuric Acid Esters / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D055815:Young Adult
chemical_list: D005419:Flavonoids; D020719:Glucuronides; D007783:Lactones; D013463:Sulfuric Acid Esters; C452422:epicatechin sulfate; C523149:epicatechin-glucuronide; D002392:Catechin; C037556:gamma-valerolactone
keywords: (−)-Epicatechin; ADME; Age; Cocoa flavanols; Pharmacokinetics