title: Chocolate matrix factors modulate the pharmacokinetic behavior of cocoa flavan-3-ol phase II metabolites following oral consumption by Sprague-Dawley rats.
abstract: The impact of carbohydrates and milk on the bioavailability of catechin (C) and epicatechin (EC) from chocolate has been previously studied. However, little data exist regarding potential modulation of the phase II metabolism by these chocolate matrix factors. The objectives of this study were to assess the impact of matrix composition on qualitative and quantitative profiles of circulating catechins and their metabolites following administration of commercially relevant chocolate confections. Sprague-Dawley rats were administered 1.5 g of a confection (reference dark, high sucrose, or milk chocolate) by intragastric gavage, and plasma samples were collected over 8 h. High-performance liquid chromatography-mass spectrometry analysis was performed to quantify C, EC, and their metabolites. The predominant metabolites were O-glucuronides (two metabolites) and O-Me-O-glucuronides (three metabolites). Plasma concentrations of metabolites were generally the highest for high sucrose treatment and lowest for milk treatment, while the reference dark treatment generally resulted in intermediate concentrations. The O-Me-(+/-)-C/EC-O-beta-glucuronide (peak 4) was significantly higher for the high sucrose treatment (2325 nM h) versus the milk treatment (1300 nM h). Additionally, C(MAX) values for (+/-)-C/EC-O-beta-glucuronide (peak 3) and two O-Me-(+/-)-C/EC-O-beta-glucuronides (peaks 4 and 6) were significantly higher for the high sucrose treatment (4012, 518, and 2518 nM, respectively) versus the milk treatment (2590, 240, and 1670 nM, respectively). Milk and sucrose appear to modulate both metabolism and plasma pharmacokinetics and, to a lesser extent, the overall bioavailability of catechins from chocolate confections.
authors.affiliation: Department of Food Science, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Neilson
authors.forename: Teryn N
authors.initials: TN
authors.lastname: Sapper
authors.forename: Elsa M
authors.initials: EM
authors.lastname: Janle
authors.forename: Ralf
authors.initials: R
authors.lastname: Rudolph
authors.forename: Nathan V
authors.initials: NV
authors.lastname: Matusheski
authors.forename: Mario G
authors.initials: MG
authors.lastname: Ferruzzi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003059:Cocos / Q000737:chemistry*; D005419:Flavonoids / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005419:Flavonoids; D010936:Plant Extracts; C404987:flavan-3-ol
references.citation: Free Radic Biol Med. 2002 Dec 15;33(12):1693-702
references.pmid: 12488137
references.citation: Br J Nutr. 2008 Oct;100(4):846-51
references.pmid: 18257943
references.citation: Am J Clin Nutr. 2005 Mar;81(3):611-4
references.pmid: 15755830
references.citation: Hypertension. 2005 Aug;46(2):398-405
references.pmid: 16027246
references.citation: J Agric Food Chem. 2001 Dec;49(12):6050-6
references.pmid: 11743807
references.citation: Br J Nutr. 2000 Nov;84(5):673-80
references.pmid: 11177180
references.citation: J Agric Food Chem. 2009 Oct 28;57(20):9418-26
references.pmid: 19780539
references.citation: J Am Coll Nutr. 2004 Jun;23(3):197-204
references.pmid: 15190043
references.citation: Br J Nutr. 2002 Jan;87(1):31-7
references.pmid: 11895312
references.citation: J Agric Food Chem. 2006 May 31;54(11):4057-61
references.pmid: 16719534
references.citation: Free Radic Biol Med. 2004 Nov 1;37(9):1351-9
references.pmid: 15454274
references.citation: Br J Nutr. 2005 Aug;94(2):170-81
references.pmid: 16115350
references.citation: J Nutr. 2008 Aug;138(8):1535S-1542S
references.pmid: 18641203
references.citation: Nature. 2003 Aug 28;424(6952):1013
references.pmid: 12944955
references.citation: Am J Clin Nutr. 2001 Nov;74(5):596-602
references.pmid: 11684527
references.citation: Am J Clin Nutr. 2009 Jun;89(6):1784-91
references.pmid: 19403635
references.citation: J Food Sci. 2007 Apr;72(3):S230-3
references.pmid: 17995820
references.citation: J Agric Food Chem. 2002 Aug 14;50(17):4852-60
references.pmid: 12166971
references.citation: Ann Nutr Metab. 2007;51(6):493-8
references.pmid: 18032884
references.citation: J Nutr. 2000 Aug;130(8S Suppl):2115S-9S
references.pmid: 10917932
references.citation: Am J Clin Nutr. 2004 Dec;80(6):1558-64
references.pmid: 15585768
references.citation: J Agric Food Chem. 2005 Aug 10;53(16):6190-4
references.pmid: 16076092
references.citation: J Agric Food Chem. 2007 Apr 18;55(8):2841-7
references.pmid: 17362030
references.citation: J Nutr. 2001 Nov;131(11):2885-91
references.pmid: 11694613
references.citation: J Agric Food Chem. 2003 Dec 3;51(25):7292-5
references.pmid: 14640573
references.citation: Biosci Biotechnol Biochem. 2000 Dec;64(12):2581-7
references.pmid: 11210120
references.citation: J Am Coll Cardiol. 2005 Oct 4;46(7):1276-83
references.pmid: 16198843
references.citation: Free Radic Res. 2006 Oct;40(10):1029-34
references.pmid: 17015247
references.citation: Am J Clin Nutr. 2008 Jul;88(1):58-63
references.pmid: 18614724
references.citation: Biosci Biotechnol Biochem. 1999 Jun;63(6):973-7
references.pmid: 10427682
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):1024-9
references.pmid: 16418281
references.citation: J Mass Spectrom. 2003 Jan;38(1):35-42
references.pmid: 12526004
references.citation: Am J Clin Nutr. 2007 Mar;85(3):709-17
references.pmid: 17344491
references.citation: Life Sci. 2003 Jul 4;73(7):857-69
references.pmid: 12798412
references.citation: Nature. 2003 Dec 18;426(6968):787-8; discussion 788
references.pmid: 14685225
references.citation: Circulation. 2007 Nov 20;116(21):2376-82
references.pmid: 17984375
references.citation: J Nutr. 2008 Sep;138(9):1671-6
references.pmid: 18716168
references.citation: Drug Metab Dispos. 1999 Feb;27(2):309-16
references.pmid: 9929521