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| Name | Class |
|---|---|
| Mars, Inc. | INDUSTRY |
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The objectives of this study are to i) describe the absorption, distribution, metabolism and excretion (ADME) and pharmacokinetic parameters of selected dietary (poly)phenols in humans; and ii) to compare the ADME and pharmacokinetic parameters of selected dietary (poly)phenols in humans.
Dietary (poly)phenols are a large group of bioactive food constituents that can be classified in flavonoids, stilbenes, lignans and phenolic acids. Flavonoids can be subclassified in different subgroups, including but not limited to flavanols (e.g. (-)-epicatechin, (+)-catechin, procyanidins, EGCG, EGC, etc) and flavones (apigenin and luteolin). Examples of flavanol-containing foods and beverages are apples, chocolate, tea, wine, berries, pomegranate and nuts. Examples of flavone-containing foods and beverages are parsley, celery, and chamomile.
(Poly)phenolic bioactives are actively investigated for their putative beneficial health effects in humans. In this context, understanding the ADME of dietary (poly)phenols is recognized as a key step to gain insight into the nutritional and biomedical relevance of this group of compounds. Understanding the ADME of polyphenols may aid towards i) the identification of metabolites as potential nutritional biomarkers of (poly)phenol consumption, ii) the identification of potential active metabolites mediating the effects observed after (poly)phenol intake, and iii) the design and execution of dietary intervention studies aiming at assess safety and efficacy of (poly)phenols.
Over the last years, significant progress has been made on the description of the ADME of certain (poly)phenols. The investigators recently described the ADME of (-)-epicatechin. However, there is still need to understand the ADME of other polyphenolic bioactives as well as the importance of the role of the gut microbiome in the metabolism of these compounds. In this context, the investigators aim at describing and comparing the ADME of dietary polyphenolic bioactives in humans. To accomplish this, the investigators propose conducting a randomized, double-masked and cross-over dietary intervention study in healthy young adult males. The investigators will evaluate the concentration of polyphenol-derived metabolites in plasma and urine after single acute intakes of polyphenol-containing test materials on 8 different test days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | Placebo Comparator | Single oral intake of flavanol-free fruit-flavored non-dairy drink |
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| Theaflavins | Experimental | Single oral intake of a fruit-flavored non-dairy drink containing a mixture of theaflavins |
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| Procyanidin Dimer B2 (DB2) | Experimental | Single oral intake of a fruit-flavored non-dairy drink containing Procyanidin Dimer B2 (DB2) |
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| (-)-Epigallocatechin-3-O-gallate (EGCG) | Experimental | Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epigallocatechin-3-O-gallate (EGCG) |
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| (-)-Epicatechin-3-O-gallate (ECG) | Experimental | Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epicatechin-3-O-gallate (ECG) |
|
| (-)-Epicatechin (EC) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Thearubigins | Other | Single oral intake of 94.9 mg of therubigins (isolated from black tea) in a flavanol-free, fruit flavored, non-dairy drink |
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| Measure | Description | Time Frame |
|---|---|---|
| Changes in the concentration of flavanol metabolites in urine. | Flavanol metabolites include gut microbiome derived metabolites include conjugates of 5-(3',4'-dihydroxyphenyl)-g-valerolactone metabolites and structurally related flavanol conjugated metabolites. | Urine collected 12h previous to intervention and up to 24 h after intervention |
| Changes in the concentration of flavanol metabolites in plasma | Flavanol metabolites include gut microbiome-derived metabolites like 5-(3',4'-dihydroxyphenyl)-g-valerolactone and structurally related flavanol conjugated metabolites. | Plasma collected before (0h) and up to 6h post intervention |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Carl L Keen, PhD | UC Davis | Principal Investigator |
| Javier I Ottaviani, PhD | Mars, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC Davis | Davis | California | 95616 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20854838 | Background | Schroeter H, Heiss C, Spencer JP, Keen CL, Lupton JR, Schmitz HH. Recommending flavanols and procyanidins for cardiovascular health: current knowledge and future needs. Mol Aspects Med. 2010 Dec;31(6):546-57. doi: 10.1016/j.mam.2010.09.008. Epub 2010 Sep 18. | |
| 22240152 | Background | Ottaviani JI, Momma TY, Kuhnle GK, Keen CL, Schroeter H. Structurally related (-)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards. Free Radic Biol Med. 2012 Apr 15;52(8):1403-12. doi: 10.1016/j.freeradbiomed.2011.12.010. Epub 2011 Dec 23. |
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Only researchers listed in the protocol and approved by the IRB will have access to IPD.
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Randomized, double-masked and cross-over dietary intervention study in healthy young adult males
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| Active Comparator |
Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epicatechin (EC) |
|
| (-)-Epigallocatechin (EGC) | Experimental | Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epigallocatechin (EGC) |
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| Thearubigins | Experimental | Single oral intake of a fruit-flavored non-dairy drink containing thearubigins |
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| Theaflavins | Other | Single oral intake of 120 µmol of an equimolar mixture of theaflavins (isolated from black tea) in a flavanol-free, fruit flavored, non-dairy drink. The theaflavin mix includes theaflavin, theaflavin-3-gallate and theaflavin-3,3'-gallate |
|
| Procyanidin Dimer B2 (DB2) | Other | Single oral intake of 120 µmol of Procyanidin Dimer B2 (DB2) (isolated from Theobroma cacao) in a flavanol-free, fruit flavored, non-dairy drink. |
|
| (-)-Epigallocatechin-3-O-gallate (EGCG) | Other | Single oral intake of 120 µmol of (-)-Epigallocatechin-3-O-gallate (EGCG)(isolated from green tea) in a flavanol-free, fruit flavored, non-dairy drink. |
|
| (-)-Epicatechin-3-O-gallate (ECG) | Other | Single oral intake of 120 µmol of (-)-Epicatechin-3-O-gallate (ECG) (isolated from green tea) in a flavanol-free, fruit flavored, non-dairy drink. |
|
| (-)-Epicatechin (EC) | Other | Single oral intake of 120 µmol of (-)-Epicatechin (EC) (isolated from green tea) in a flavanol-free, fruit flavored, non-dairy drink. |
|
| (-)-Epigallocatechin (EGC) | Other | Single oral intake of 120 µmol of (-)-Epigallocatechin (EGC) (isolated from green tea) in a flavanol-free, fruit flavored, non-dairy drink. |
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| Control | Other | Single oral intake of a flavanol-free, fruit flavored, non-dairy drink. |
|
| 6946775 | Background | Koster H, Halsema I, Scholtens E, Knippers M, Mulder GJ. Dose-dependent shifts in the sulfation and glucuronidation of phenolic compounds in the rat in vivo and in isolated hepatocytes. The role of saturation of phenolsulfotransferase. Biochem Pharmacol. 1981 Sep 15;30(18):2569-75. doi: 10.1016/0006-2952(81)90584-0. No abstract available. |
| 16794446 | Background | McCullough ML, Chevaux K, Jackson L, Preston M, Martinez G, Schmitz HH, Coletti C, Campos H, Hollenberg NK. Hypertension, the Kuna, and the epidemiology of flavanols. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S103-9; discussion 119-21. doi: 10.1097/00005344-200606001-00003. |
| 16198843 | Background | Heiss C, Kleinbongard P, Dejam A, Perre S, Schroeter H, Sies H, Kelm M. Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers. J Am Coll Cardiol. 2005 Oct 4;46(7):1276-83. doi: 10.1016/j.jacc.2005.06.055. |
| 22794138 | Background | Del Rio D, Rodriguez-Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A. Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal. 2013 May 10;18(14):1818-92. doi: 10.1089/ars.2012.4581. Epub 2012 Aug 27. |
| 22378733 | Background | Ottaviani JI, Kwik-Uribe C, Keen CL, Schroeter H. Intake of dietary procyanidins does not contribute to the pool of circulating flavanols in humans. Am J Clin Nutr. 2012 Apr;95(4):851-8. doi: 10.3945/ajcn.111.028340. Epub 2012 Feb 29. |
| ID | Term |
|---|---|
| C056068 | theaflavin |
| C045651 | epigallocatechin gallate |
| C062669 | epicatechin gallate |
| D002392 | Catechin |
| C057580 | gallocatechol |
| ID | Term |
|---|---|
| D002839 | Chromans |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005419 | Flavonoids |
| D002867 | Chromones |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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