Absorption and Metabolism of Dietary Cocoa Procyanidins in Humans

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Contribution of Dietary Cocoa Procyanidins to the Systemic Presence of Flavanols Metabolites in Humans

Conditions
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Healthy

Intervention / Treatment
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* Other: Flavanol- and procyanidins-containing drink
* Other: Procyanidins-containing drink
* Other: Flavanol-containing drink


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Flavanol and procyanidins<br> | Other: Flavanol- and procyanidins-containing drink<br>* Single oral intake of a cocoa-based dairy drink containing flavanols [monomer] and procyanidins [dimers to decamers]<br>* Other names: Cocoa-based dairy drink;|
| Experimental: Flavanols only<br> | Other: Flavanol-containing drink<br>* Single oral intake of a cocoa-based dairy drink containing flavanols [monomers]<br>* Other names: cocoa-based dairy drink;|
| Experimental: Procyanidins only<br> | Other: Procyanidins-containing drink<br>* Single oral intake of a ocoa-based dairy drink containing procyanidins [dimers to decamers]<br>* Other names: Cocoa-based dairy drink;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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flavanols, procyanidins, absorption, cocoa polyphenols, Flavanol and procyanidin absorption in healthy volunteers