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The purpose of this study is to determine whether or not the intake of dietary procyanidins (oligomers of flavanols) contribute to the systemic presence of flavanols in healthy humans.
Flavanols and their oligomeric derivatives, the procyanidins, are plant-derived compounds normally present in the human diet. Accumulating data demonstrate a causal role for flavanols in mediating the cardiovascular benefits associated with the consumption of flavanol-/procyanidin-containing foods. Evidence for a direct, causal role for procyanidins in this context is far less profound. As this is often based on the poor absorption of procyanidins, it has been proposed that procyanidins may indirectly contribute to the systemic presence of bioactive compounds via derivatives generated from the breakdown or catabolism of procyanidins in the gastrointestinal tract. These postulated 'breakdown products' include: i) flavanols, putatively generated by acid hydrolysis in the stomach, and ii) series of phenolic compounds, including 5-(3,4-dihydroxyphenyl)-gamma-valerolactone, that are produced from procyanidin catabolism by the gut microbiome. Verification or rejection of these suppositions could significantly impact the interpretation of epidemiological-/dietary intervention data, and the design of food-content data bases. To address this question, healthy volunteers will consume specially designed cocoa-based dairy drinks containing flavanols and procyanidins (dimers to decamers) either together or individually.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Flavanol and procyanidins | Active Comparator |
| |
| Flavanols only | Experimental |
| |
| Procyanidins only | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Flavanol- and procyanidins-containing drink | Other | Single oral intake of a cocoa-based dairy drink containing flavanols [monomer] and procyanidins [dimers to decamers] |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area under the curve described by the concentration of flavanol metabolites in plasma versus time | The concentration of flavanol metabolites in plasma is expressed in nmol/L. Flavanol metabolites encompass a series of O-sulfonated, O-glucuronidated and O-methylated flavanol derivatives generated in the gastrointestinal tract and liver after flavanol absorption. | After consumption at time points 0, 1, 2 and 4 h |
| Peak plasma concentration of flavanol metabolites | The concentration of flavanol metabolites in plasma is expressed in nmol/L. Flavanol metabolites encompass a series of O-sulfonated, O-glucuronidated and O-methylated flavanol derivatives generated in the gastrointestinal tract and liver after flavanol absorption. | After consumption at time points 0, 1, 2 and 4 h |
| Measure | Description | Time Frame |
|---|---|---|
| Amount of flavanol metabolites excreted in urine | The amount of flavanol metabolites excreted in urine is expressed in µmol. Flavanol metabolites encompass a series of O-sulfonated, O-glucuronidated and O-methylated flavanol derivatives generated in the gastrointestinal tract and liver after flavanol absorption. | urine collected up to 24h post-consumption |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Carl L Keen, PhD | Department of Nutition, University of California Davis | Study Chair |
| Javier I Ottaviani, PhD | Department of Nutrition, University of California Davis | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ragle Facility-UC Davis | Davis | California | 95616 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20852295 | Background | Heiss C, Keen CL, Kelm M. Flavanols and cardiovascular disease prevention. Eur Heart J. 2010 Nov;31(21):2583-92. doi: 10.1093/eurheartj/ehq332. Epub 2010 Sep 18. | |
| 15640486 | Background | Manach C, Williamson G, Morand C, Scalbert A, Remesy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr. 2005 Jan;81(1 Suppl):230S-242S. doi: 10.1093/ajcn/81.1.230S. |
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| Procyanidins-containing drink | Other | Single oral intake of a ocoa-based dairy drink containing procyanidins [dimers to decamers] |
|
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| Flavanol-containing drink | Other | Single oral intake of a cocoa-based dairy drink containing flavanols [monomers] |
|
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| Amount of 5-(3,4-dihydroxyphenyl)-gamma-valerolactone metabolites in urine | The amount of 5-(3,4-dihydroxyphenyl)-gamma-valerolactone metabolites excreted in urine is expressed in µmol. 5-(3,4-dihydroxyphenyl)-gamma-valerolactone metabolites encompass a series of O-sulfonated and O-glucuronidated derivatives generated in the gastrointestinal tract and liver after 5-(3,4-dihydroxyphenyl)-gamma-valerolactone absorption. | urine collected up to 24 h post-consumption |
| 20854839 | Background | Crozier A, Del Rio D, Clifford MN. Bioavailability of dietary flavonoids and phenolic compounds. Mol Aspects Med. 2010 Dec;31(6):446-67. doi: 10.1016/j.mam.2010.09.007. Epub 2010 Sep 18. |
| 12399286 | Background | Rios LY, Bennett RN, Lazarus SA, Remesy C, Scalbert A, Williamson G. Cocoa procyanidins are stable during gastric transit in humans. Am J Clin Nutr. 2002 Nov;76(5):1106-10. doi: 10.1093/ajcn/76.5.1106. |
| 12324293 | Background | Holt RR, Lazarus SA, Sullards MC, Zhu QY, Schramm DD, Hammerstone JF, Fraga CG, Schmitz HH, Keen CL. Procyanidin dimer B2 [epicatechin-(4beta-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa. Am J Clin Nutr. 2002 Oct;76(4):798-804. doi: 10.1093/ajcn/76.4.798. |
| 14556848 | Background | Gonthier MP, Donovan JL, Texier O, Felgines C, Remesy C, Scalbert A. Metabolism of dietary procyanidins in rats. Free Radic Biol Med. 2003 Oct 15;35(8):837-44. doi: 10.1016/s0891-5849(03)00394-0. |
| 22378733 | Derived | 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. |