Bioavailability of Hydroxytyrosol in Humans Co-administered With EPA (HydroxyOmegaBd)

Hydroxytyrosol Bioavailability in Humans: A Comparative Study of Three EPA-Enriched Formulations

The primary objective of this study is to evaluate the optimal formulation of a natural nutraceutical whose daily consumption at nutritional doses may confer benefits for cardiovascular health. This nutraceutical combines an omega-3 fatty acid (eicosapentaenoic acid, EPA) with hydroxytyrosol (a potent antioxidant found in olives and extra virgin olive oil). The study will allow to compare how and to what extent hydroxytyrosol is absorbed when co-administered the omega-3 fatty acid in capsules across three different formulations.

Study Overview

• Status: Completed
• Conditions: Healthy; Young
• Intervention / Treatment: Dietary supplement: Hydroxytyrosol acetate (HT-Ac); Dietary supplement: Hydroxytyrosol eicosapentanoate (HT-EPA); Dietary supplement: Oleacore®

Detailed Description

12 healthy male and female participants will consume various formulations corresponding to three nutraceuticals developed: hydroxytyrosol acetate (HT-Ac), hydroxytyrosol eicosapentanoate (HT-EPA), and hydroxytyrosol extract (Oleacore®) with EPA. One week prior to the intervention, participants will be instructed to refrain from consuming extra virgin olive oil or olives as the primary dietary sources of hydroxytyrosol (wash-out phase). Since three types of nutraceuticals will be evaluated, the study will take place over three separate days, with one week between each intervention.

On each intervention day, following an overnight fast, volunteers will randomly consume one of the nutraceuticals. A polyphenol-free diet will be provided during the 24 hours after the nutraceutical intake.

Blood samples will be collected right before the nutracetical intake at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-consumption. Urine samples will also be collected in 24-hour collection containers containing 0.5 g of ascorbic acid, at the following intervals: -2 to 0 hours (baseline), 0-3 hours, 3-6 hours, 6-10 hours, and 10-24 hours. All of these samples will be stored at -80ºC until analysis.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28040
    • ICTAN-CSIC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age: 18 to 45 years old
• Body Mass Index (BMI): 18 to 25 kg/m²

Exclusion Criteria:

• Presence of chronic illnesses
• Currently undergoing pharmacological treatment
• Smoking
• Pregnancy
• Following a vegetarian or vegan diet

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HT-Ac → HT-EPA → Oleacore®; Group 1 will consume HT-Ac in the first week, HT-EPA in the second week and Oleacore® in the third week.	Dietary supplement: Hydroxytyrosol acetate (HT-Ac); Hydroxytyrosol acetate (15 mg) orally co-administered with 2 g EPA; Dietary supplement: Hydroxytyrosol eicosapentanoate (HT-EPA); Oral intake of hydroxytyrosol eicosapentanoate (15 mg) solubilized in an EPA-enriched oil matrix.; Dietary supplement: Oleacore®; Oleacore® (containing 15 mg of hydroxytyrosol) orally co-administered with 2 g EPA
Experimental: HT-EPA → Oleacore® → HT-Ac; Group 2 will consume HT-EPA in the first week, Oleacore® in the second week and HT-Ac in the third week.	Dietary supplement: Hydroxytyrosol acetate (HT-Ac); Hydroxytyrosol acetate (15 mg) orally co-administered with 2 g EPA; Dietary supplement: Hydroxytyrosol eicosapentanoate (HT-EPA); Oral intake of hydroxytyrosol eicosapentanoate (15 mg) solubilized in an EPA-enriched oil matrix.; Dietary supplement: Oleacore®; Oleacore® (containing 15 mg of hydroxytyrosol) orally co-administered with 2 g EPA
Experimental: Oleacore® → HT-Ac → HT-EPA; Group 3 will consume Oleacore® in the first week, HT-Ac in the second week and HT-EPA in the third week.	Dietary supplement: Hydroxytyrosol acetate (HT-Ac); Hydroxytyrosol acetate (15 mg) orally co-administered with 2 g EPA; Dietary supplement: Hydroxytyrosol eicosapentanoate (HT-EPA); Oral intake of hydroxytyrosol eicosapentanoate (15 mg) solubilized in an EPA-enriched oil matrix.; Dietary supplement: Oleacore®; Oleacore® (containing 15 mg of hydroxytyrosol) orally co-administered with 2 g EPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Targeted and untargeted metabolomics	The determination of HT metabolites in plasma and urine of the healthy volunteers following the consumption of nutraceuticals will be carried out using both targeted and untargeted metabolomics through high-performance liquid chromatography coupled to an Accurate-Mass Quadrupole Time-of-Flight (QToF) with ESI-Jet Stream Technology (HPLC-ESI-QToF, Agilent Technologies). Additionally, three types of nutraceuticals (EPA-HT, EPA+HT-Ac and EPA-Oleacore®) will be tested in order to evaluate the HT bioavailability comparatively.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ox-LDL as marker of oxidative status	Differences between non-supplemented subjects and those supplemented with HT-Ac, HT-EPA, and Oleacore®, analyzed across different blood collection times.	Up to 2 months

Collaborators and Investigators

• Sponsor: National Research Council, Spain
• Collaborators: Olivenova Health Sl
• Investigators: Principal Investigator: Raquel Mateos Briz Tenured Scientist, 1

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2024
• Primary Completion (Actual): December 4, 2024
• Study Completion (Actual): December 4, 2024

Study Registration Dates

• First Submitted: December 10, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): December 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Bioavailability; omega-3; nutraceutical; hydroxytyrosol; nutrikinetics
• Additional Relevant MeSH Terms: Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Antioxidants; Protective Agents; Anti-Infective Agents, Local; Disinfectants; 3,4-dihydroxyphenylethanol; Phenylethyl Alcohol
• Other Study ID Numbers: HYDROXYOMEGA-BIOAVAILABILITY

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
• product manufactured in and exported from the U.S.: No