Evaluation of Bioavailability and Metabolism of Diet Phenolic Compounds (dopet4)

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08017
    • Consorci Parc de Salut Mar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sub-study A : olive oil, wine, both, or water (placebo).; 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; 25 mL of extra virgin olive oil; Other: Administration of red wine; 150 mL or Red Wine; Other: Combination of red wine and olive oil; 150 mL of Red wine + 25 mL of Extra Virgin Olive oil will be administred at the same time; Other: Water; Mineral water will be given as placebo
Experimental: Sub-study B : three types of beer, and wine; 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; 150 mL or Red Wine; Other: Dark beer; 250 mL of IPA beer (alcohol 8.5% vol); Other: Light Beer; 250 mL of blonde ale beer (alcohol 4,5% vol); Other: Alcohol free Beer; 250 mL of alcohol free beer (alcohol 0.0% vol)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Parc de Salut Mar
• Investigators: Principal Investigator: Rafael de la Torre Fornell, Dr, IMIM (Hospital del Mar Medical Research Institute)

Publications and helpful links

General Publications

• Wu L, Sun D. Adherence to Mediterranean diet and risk of developing cognitive disorders: An updated systematic review and meta-analysis of prospective cohort studies. Sci Rep. 2017 Jan 23;7:41317. doi: 10.1038/srep41317.
• Rodriguez-Morato J, Robledo P, Tanner JA, Boronat A, Perez-Mana C, Oliver Chen CY, Tyndale RF, de la Torre R. CYP2D6 and CYP2A6 biotransform dietary tyrosol into hydroxytyrosol. Food Chem. 2017 Feb 15;217:716-725. doi: 10.1016/j.foodchem.2016.09.026. Epub 2016 Sep 7.
• Perez-Mana C, Farre M, Rodriguez-Morato J, Papaseit E, Pujadas M, Fito M, Robledo P, Covas MI, Cheynier V, Meudec E, Escudier JL, de la Torre R. Moderate consumption of wine, through both its phenolic compounds and alcohol content, promotes hydroxytyrosol endogenous generation in humans. A randomized controlled trial. Mol Nutr Food Res. 2015 Jun;59(6):1213-6. doi: 10.1002/mnfr.201400842. Epub 2015 Apr 27.
• Granados-Principal S, Quiles JL, Ramirez-Tortosa CL, Sanchez-Rovira P, Ramirez-Tortosa MC. Hydroxytyrosol: from laboratory investigations to future clinical trials. Nutr Rev. 2010 Apr;68(4):191-206. doi: 10.1111/j.1753-4887.2010.00278.x.
• Oliveras-Lopez MJ, Molina JJ, Mir MV, Rey EF, Martin F, de la Serrana HL. Extra virgin olive oil (EVOO) consumption and antioxidant status in healthy institutionalized elderly humans. Arch Gerontol Geriatr. 2013 Sep-Oct;57(2):234-42. doi: 10.1016/j.archger.2013.04.002. Epub 2013 May 1.
• Weinbrenner T, Fito M, de la Torre R, Saez GT, Rijken P, Tormos C, Coolen S, Albaladejo MF, Abanades S, Schroder H, Marrugat J, Covas MI. Olive oils high in phenolic compounds modulate oxidative/antioxidative status in men. J Nutr. 2004 Sep;134(9):2314-21. doi: 10.1093/jn/134.9.2314.
• Castaner O, Covas MI, Khymenets O, Nyyssonen K, Konstantinidou V, Zunft HF, de la Torre R, Munoz-Aguayo D, Vila J, Fito M. Protection of LDL from oxidation by olive oil polyphenols is associated with a downregulation of CD40-ligand expression and its downstream products in vivo in humans. Am J Clin Nutr. 2012 May;95(5):1238-44. doi: 10.3945/ajcn.111.029207. Epub 2012 Mar 21.
• Hernaez A, Fernandez-Castillejo S, Farras M, Catalan U, Subirana I, Montes R, Sola R, Munoz-Aguayo D, Gelabert-Gorgues A, Diaz-Gil O, Nyyssonen K, Zunft HJ, de la Torre R, Martin-Pelaez S, Pedret A, Remaley AT, Covas MI, Fito M. Olive oil polyphenols enhance high-density lipoprotein function in humans: a randomized controlled trial. Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):2115-9. doi: 10.1161/ATVBAHA.114.303374. Epub 2014 Jul 24.
• Ruano J, Lopez-Miranda J, de la Torre R, Delgado-Lista J, Fernandez J, Caballero J, Covas MI, Jimenez Y, Perez-Martinez P, Marin C, Fuentes F, Perez-Jimenez F. Intake of phenol-rich virgin olive oil improves the postprandial prothrombotic profile in hypercholesterolemic patients. Am J Clin Nutr. 2007 Aug;86(2):341-6. doi: 10.1093/ajcn/86.2.341.
• Ruano J, Lopez-Miranda J, Fuentes F, Moreno JA, Bellido C, Perez-Martinez P, Lozano A, Gomez P, Jimenez Y, Perez Jimenez F. Phenolic content of virgin olive oil improves ischemic reactive hyperemia in hypercholesterolemic patients. J Am Coll Cardiol. 2005 Nov 15;46(10):1864-8. doi: 10.1016/j.jacc.2005.06.078. Epub 2005 Oct 24.
• De la Torre R, Corella D, Castaner O, Martinez-Gonzalez MA, Salas-Salvado J, Vila J, Estruch R, Sorli JV, Aros F, Fiol M, Ros E, Serra-Majem L, Pinto X, Gomez-Gracia E, Lapetra J, Ruiz-Canela M, Basora J, Asensio EM, Covas MI, Fito M. Protective effect of homovanillyl alcohol on cardiovascular disease and total mortality: virgin olive oil, wine, and catechol-methylation. Am J Clin Nutr. 2017 Jun;105(6):1297-1304. doi: 10.3945/ajcn.116.145813. Epub 2017 Apr 26. Erratum In: Am J Clin Nutr. 2018 Oct 1;108(4):903-906.

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2018
• Primary Completion (Actual): February 27, 2019
• Study Completion (Actual): February 27, 2019

Study Registration Dates

• First Submitted: July 10, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): March 5, 2020
• Last Update Submitted That Met QC Criteria: March 4, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: IMIMFTCL/DOPET4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No