Evaluation of Bioavailability and Metabolism of Diet Phenolic Compounds

Study Overview
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Brief Summary
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This study aims at studying in depth the absorption and metabolism of phenolic compounds of olive oil, wine and beer. This study is divided into 2 sub-studies in order to evaluate each one of the objectives.

Detailed Description
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The study is divided in two sub-studies to explore each objective. One the one hand, a group of people will drink olive oil, or wine, or both. This is done to see if combining these two drinks will improve the absorption and bioavailibility of phenolic compounds that they contain, promoting by synergy their antioxidant activity at a postprandial level. The main compounds studied are the Resveratrol (RSVT), the Hydroxytyrosol (HT), tyrosol (TIR) and their metabolits. One the other hand, an group of people will drink 3 different beers ( with 3 different degrees of alcohol), or wine, in order to study the absorption of TIR in relation to the alcohol degree. It also aims at assessing if the gas contained in beer contributes to TIR absorption. At different times after the administration of drinks, urine and blood samples will be collected.

Official Title
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Evaluation of Bioavailability and Metabolism of Diet Phenolic Compounds

Conditions
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Healthy

Intervention / Treatment
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* Other: Administration of olive oil
* Other: Administration of red wine
* Other: Combination of red wine and olive oil
* Other: Water
* Other: Dark beer
* Other: Light Beer
* Other: Alcohol free Beer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women from 18 to 45 years old. Understand and accepting the procedures of the trial and sign an informed consent. Have a history and physical exams that show that there is no organic issue, and an analysis and ECG in the normal limits. Have an BMI between 18.5 and 30 kg/m2. caucasian race Exclusion Criteria: Smokers Persons with chronical disease Persons with BMI>30 or <18.5 kg/m2. Persons with history of multiple allergies or obvious intestinal, hepatic, renal issues or other problems that could suppose a deterioration of absorption, distribution or metabolism of polyphenols. Persons who take anti-oxidant products, including vitamins, herbal medication or dietetics complementation that could interfere in the study objectives. Persons with restrictive diet (including vegetarian diet). Persons with history of hypersensibility or intolerance to alcohol. Persons with a daily consumption of alcohol >50g or who have consumed illegal drug in the month preceding the study. Persons who have participated in an other clinical trial the month preceding the study. Persons who have done a blood donation during the last 3 months before the beginning of the study (only appliable to the subjects of A sub-study). Persons who have a positive serology for B or C hepatitis or HIV. Pregnant or breastfeeding women, or any other situation prohibiting alcohol consumption. Persons who have consummed NSAIDs (especially acetylsalicylic acid) or antioxidants or vitamin complementation, during the 2 weeks preceding the beginning of the study. Illiterate persons

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A 40 people group of healthy men and women. Two Cohorts group of 20 healthy volunteers of both genders.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sub-study A : olive oil, wine, both, or water (placebo).<br>After being selected, subjects will do 4 experimental sessions (each separated by 3 days minimum) in which ones they will drink olive oil, red wine, red wine and olive oil, or water (placebo). The order of the experimental sessions will be drawn. | Other: Administration of olive oil<br>* 25 mL of extra virgin olive oil<br>Other: Administration of red wine<br>* 150 mL or Red Wine<br>Other: Combination of red wine and olive oil<br>* 150 mL of Red wine + 25 mL of Extra Virgin Olive oil will be administred at the same time<br>Other: Water<br>* Mineral water will be given as placebo<br>|
| Experimental: Sub-study B : three types of beer, and wine<br>The subjects will do 4 experimental sessions (each separated by 3 days minimum) in wich ones they will drink a beer (250mL) or wine (150mL). The order of the experimental sessions will be drawn. | Other: Administration of red wine<br>* 150 mL or Red Wine<br>Other: Dark beer<br>* 250 mL of IPA beer (alcohol 8.5% vol)<br>Other: Light Beer<br>* 250 mL of blonde ale beer (alcohol 4,5% vol)<br>Other: Alcohol free Beer<br>* 250 mL of alcohol free beer (alcohol 0.0% vol)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sub-study A : Basal dosing of urinary phenolic compounds and their metabolites concentrations |  | 2 hours before administration to administration (-2 to 0 hours) | 
| Sub-study A : Basal dosing of urinary phenolic compounds and their metabolites concentrations |  | 0-2 hours; 2-4 hours; 4-6 hours; 6-12 hours; 12-24 hours post administration | 
| Sub-study A : Postprandial dosing of plasmatic phenolic compounds and their metabolites concentrations |  | baseline, 30 minutes; 45 minutes; 1 hours; 1.5 hours; 2 hours; 6 hours post administration | 
| Sub-study B : Basal dosing of urinary phenolic compounds and their metabolites concentrations |  | 2 hours before administration to administration (-2 to 0 hours) | 
| Sub-study B : Postprandial dosing of urinary phenolic compounds and their metabolites concentrations |  | 0-2 hours; 2-4 hours; 4-6 hours; 6-12 hours; 12-24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sub-study A : Postprandial dosing of plasmatic glucose |  | baseline, 30 minutes; 45 minutes; 1 hours; 1.5 hours; 2 hours; 6 hours post administration | 
| Sub-study A : Postprandial dosing of plasmatic insulin |  | baseline, 30 minutes; 45 minutes; 1 hours; 1.5 hours; 2 hours; 6 hours post administration | 
| Sub-study A : Postprandial dosing of plasmatic total cholesterol |  | baseline, 30 minutes; 45 minutes; 1 hours; 1.5 hours; 2 hours; 6 hours post administration | 
| Sub-study A : Postprandial dosing of plasmatic triglyceride |  | baseline, 30 minutes; 45 minutes; 1 hours; 1.5 hours; 2 hours; 6 hours post administration | 
| Sub-study A : Postprandial dosing of plasmatic LDL |  | baseline, 30 minutes; 45 minutes; 1 hours; 1.5 hours; 2 hours; 6 hours post administration | 
| Sub-study A : Postprandial dosing of plasmatic oxidated-LDL |  | baseline, 30 minutes; 45 minutes; 1 hours; 1.5 hours; 2 hours; 6 hours post administration | 
| Sub-study A : Postprandial dosing of plasmatic HDL concentrations. |  | baseline, 30 minutes; 45 minutes; 1 hours; 1.5 hours; 2 hours; 6 hours post administration | 
| Sub-study A : Basal cardiovascular activity : blood pressure |  | 15 minutes before administration | 
| Sub-study A : Basal cardiovascular activity: heart rate |  | 15 minutes before administration | 
| Sub-study A : Basal cardiovascular activity : endothelial function. | Endothelial function will be assessed as flow-mediated dilation using endoPAT 2000 (Itamar Medical device). Flow-mediated dilation is the most widely used method to test endothelial function since it is non-invasive, and measures by ultrasounds the response to increased shear stress, commonly in the brachial artery | 15 minutes before administration | 
| Sub-study A : Postprandial cardiovascular activity : blood pressure |  | 1 hour and 2 hours post administration | 
| Sub-study A : Postprandial cardiovascular activity : heart rate |  | 1 hour and 2 hours post administration | 
| Sub-study A : Postprandial cardiovascular activity: endothelial function. | Endothelial function will be assessed as flow-mediated dilation using endoPAT 2000 (Itamar Medical device). Flow-mediated dilation is the most widely used method to test endothelial function since it is non-invasive, and measures by ultrasounds the response to increased shear stress, commonly in the brachial artery | 1 hour and 2 hours post administration | 
| Sub-study B : Basal cardiovascular activity : blood pressure |  | 15 minutes before administration | 
| Sub-study B : Basal cardiovascular activity: heart rate. |  | 15 minutes before administration | 
| Sub-study B : Postprandial cardiovascular activity : blood pressure |  | 30 minutes, 1hour, 2 hours and 4 hours post administration | 
| Sub-study B : Postprandial cardiovascular activity: heart rate. |  | 30 minutes, 1hour, 2 hours and 4 hours post administration | 
| Sub-study B : Concentration of alcohol in the exhaled breath | Blood alcohol (ethanol) concentration is correlated with the concentration of alcohol in the exhaled breath at end-exhalation (BrAC). It is a non-invasive method that has been used to quantify alcohol intake. | 15 minutes before administration | 
| Sub-study B : Postprandial Concentration of alcohol in the exhaled breath | Blood alcohol (ethanol) concentration is correlated with the concentration of alcohol in the exhaled breath at end-exhalation (BrAC). It is a non-invasive method that has been used to quantify alcohol intake. | 30 minutes, 1hour, 2 hours and 4 hours post administration | 
| Sub-study B : Basal isoxanthohumol urinary concentration | Isoxanthohumol is a biomarker of beer consumption. | 2 hours before administration to administration (-2 to 0 hours) | 
| Sub-study B : Postprandial isoxanthohumol urinary concentration | Isoxanthohumol is a biomarker of beer consumption. | 0-2 hours; 2-4 hours; 4-6 hours; 6-12 hours; 12-24 hours post administration | 
| Sub-study B : Basal urinary creatinine concentration |  | 2 hours before administration to administration (-2 to 0 hours) | 
| Sub-study B : Basal urinary urinary pH. | pH is a logarithmic scale used to specify the acidity or basicity of an aqueous solution. | 2 hours before administration to administration (-2 to 0 hours) | 
| Sub-study B : Postprandial urinary creatinine concentration |  | 0-2 hours; 2-4 hours; 4-6 hours; 6-12 hours; 12-24 hours post administration | 
| Sub-study B : Postprandial urinary urinary pH. | pH is a logarithmic scale used to specify the acidity or basicity of an aqueous solution. | 0-2 hours; 2-4 hours; 4-6 hours; 6-12 hours; 12-24 hours post administration |