Clinical trial NCT01483508: Absorption and Metabolism of Dietary Cocoa Procyanidins in Humans
Official title: Contribution of Dietary Cocoa Procyanidins to the Systemic Presence of Flavanols Metabolites in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: flavanols
procyanidins
absorption
cocoa polyphenols
Flavanol and procyanidin absorption in healthy volunteers
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2011-12-01
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* A normal blood chemistry and liver function
* Fasting blood cholesterol and triglycerides \< 300 mg/dl and \< 3.0 mmol/l, respectively
* BMI \< 30 kg/m2 will be considered.
* Volunteers must be able to read and speak English fluently, and thus, fully understand the researchers, research protocols, and their rights as a research volunteer.

Exclusion Criteria:

* A history of cardiovascular disease, stroke, uncontrolled hypertension (\> 160/90 mm), renal, hepatic, or thyroid disease, GI tract disorders, previous GI surgery, metabolic syndrome, diabetes, taking cholesterol-lowering medication, hormone replacement therapy, antioxidant supplements, on aspirin therapy or taking anticoagulants, or on a medically prescribed diet.
* A history of psychiatric illness or an allergy to peanuts.

Primary outcomes:
measure: Area under the curve described by the concentration of flavanol metabolites in plasma versus time
timeFrame: After consumption at time points 0, 1, 2 and 4 h
measure: Peak plasma concentration of flavanol metabolites
timeFrame: After consumption at time points 0, 1, 2 and 4 h
Secondary outcomes:
measure: Amount of flavanol metabolites excreted in urine
timeFrame: urine collected up to 24h post-consumption
measure: Amount of 5-(3,4-dihydroxyphenyl)-gamma-valerolactone metabolites in urine
timeFrame: urine collected up to 24 h post-consumption
Other outcomes:
Locations:
city: Davis
country: United States
facility: Ragle Facility-UC Davis
state: California
Study officials:
affiliation: Department of Nutition, University of California Davis
name: Carl L Keen, PhD
role: STUDY_CHAIR
affiliation: Department of Nutrition, University of California Davis
name: Javier I Ottaviani, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.