Effects of Enzymatic Digestion and Probiotic on Oleuropein Bioavailability

This is a 3-arms randomized-controlled, parallel group, single center, double-blind study investigating the bioavailability of olive oil extract (OLE) in two different OLE formulations (enzymatically treated and co-administered with a probiotic) compared to original OLE formulation in healthy adult subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Dietary supplement: OLE enzymatically treated; Dietary supplement: OLE + probiotic; Dietary supplement: OLE

Detailed Description

Male or female healthy adults between 25 and 65 years of age will be randomized into one of the 3 following groups to receive:

1. Capsule of OLE + 1 stick of maltodextrin
2. Capsule of OLE enzymatically treated + 1 stick of maltodextrin
3. Capsule OLE + 1 stick of probiotic

52 subjects will be randomized to achieve 15 subjects per group to complete the trial.

The study will involve 3 phases:

1. PK1 (all subjects will receive one capsule of OLE in the morning and blood samples will be collected at different timepoints for 24h) followed by a washout period of 1 day
2. 3 weeks intervention (subjects will receive the product thy have benn assigned to) followed by a wash-out period of 3 days
3. PK2 period (subjects will receive one capsule the product thy have benn assigned to

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Murcia, Spain, 30107
    • Universidad Católica San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Willing and able to sign written informed consent prior to trial entry
2. Male or female healthy adults between 25 and 65 years of age
3. Body Mass Index (BMI) within the range 18.5 - 29.9 (both inclusive)
4. In good health as determined by medical judgment and medical history

Exclusion Criteria:

1. Any food allergy/intolerance
2. Subjects not willing and/or not able to comply with scheduled visits and the requirements of the study protocol
3. Taking or anticipated initiation of any lipid-modifying or blood-clotting medication e.g. statins, cholesterol lowering
4. Smokers
5. Alcohol intake higher than 2 servings per day (one serving is 0.4 dL of strong alcohol, 1 dL of wine, or 3 dL of beer) or drug abuse
6. Receiving or having received antibiotics in the past 4 weeks prior to the day of inclusion
7. Overly imbalanced or restrictive diet (e.g. hyperproteic, vegan, ketogenic, etc.)
8. Hormonal treatment for women linked to menopause (contraceptive treatment accepted)
9. Pregnancy or breastfeeding
10. Supplements or foods containing probiotics (yogurts allowed)
11. Currently participating or having participated in another clinical trial within 4 weeks prior to trial start

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OLE enzymatically treated; Participants will receive 1 capsule of OLE enzymatically treated + 1 stick of maltodextrin each day in the morning for 21 days	Dietary supplement: OLE enzymatically treated; OLE (Olive leaf extract ) enzymatically treated + maltodextrin
Experimental: OLE + probiotic; Participants will receive 1 capsule of OLE + 1 stick of probiotic each day in the morning for 21 days	Dietary supplement: OLE + probiotic; OLE (Olive leaf extract) co-administered with probiotic
Active Comparator: OLE; Participants will receive 1 capsule of OLE + 1 stick of maltodextrin each day in the morning for 21 days	Dietary supplement: OLE; OLE (Olive leaf extract) + maltodextrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-24h of individual blood oleuropein metabolites during PK2 period	AUC0-24h (concentration/time curve) of individual blood oleuropein metabolites during PK2 period	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax during PK2 period	Cmax of total and individual oleuropein metabolites during PK2 period	24 hours
Tmax during PK2 period	Tmax of total and individual oleuropein metabolites during PK2 period	24 hours
T1/2 during PK2 period	T1/2 of total and individual oleuropein metabolites during PK2 period	24 hours
Levels of total and individual oleuropein metabolites in urine at PK2	Levels of total and individual oleuropein metabolites excreted in the urine collected over 24 hours during PK2	24 hours
AUC0-24h during PK1	AUC0-24h (concentration/time curve) of individual blood oleuropein metabolites during PK1 period	24 hours
Cmax during PK1	Cmax of total and individual blood oleuropein metabolites during PK1 period	24 hours
Tmax during PK1	Tmax of total and individual blood oleuropein metabolites during PK1 period	24 hours
T1/2 during PK1	T1/2 of total and individual blood oleuropein metabolites during PK1 period	24 hours
Levels of total and individual oleuropein metabolites in urine at PK1	Levels of total and individual oleuropein metabolites excreted in the urine collected over 24 hours during PK1	24 hours
Change in gut microbiota bacterial population diversity	Change from baseline to end of the 3-week intervention period of gut microbiota bacterial population diversity (16SrDNA sequencing)	3 weeks
Change in levels of faecal oleuropein metabolites	Change from baseline to end of the 3-week intervention period of faecal oleuropein metabolites	3 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of gut microbiota faecal short chain fatty acids	Change from baseline to end of the 3-week intervention period of gut microbiota faecal short chain fatty acids (acetate, propionate, butyrate) & lactate	3 weeks
Change of gut microbiota faecal branched chain fatty acids	Change from baseline to end of the 3-week intervention period of gut microbiota faecal branched chain fatty acids (isobutyrate, isovalerate & isocaproate)	3 weeks
Change of gut microbiota faecal ammonium production	Change from baseline to end of the 3-week intervention period of gut microbiota faecal ammonium production	3 weeks
Blood levels of total cholesterol	Change from baseline to the end of the 3-week intervention period of total cholesterol levels	3 weeks
Blood levels of LDL	Change from baseline to the end of the 3-week intervention period of LDL levels	3 weeks
Blood levels of HDL	Change from baseline to the end of the 3-week intervention period of HDL levels	3 weeks
Blood levels of ALAT	Change from baseline to the end of the 3-week intervention period of ALAT levels	3 weeks
Blood levels of ASAT	Change from baseline to the end of the 3-week intervention period of ASAT levels	3 weeks
Blood levels of creatinine	Change from baseline to the end of the 3-week intervention period of creatinine levels	3 weeks
Blood levels of glucose	Change from baseline to the end of the 3-week intervention period of glucose levels	3 weeks
Blood levels of triglycerides	Change from baseline to the end of the 3-week intervention period of triglycerides levels	3 weeks
Blood levels of bone biomarkers	Change from baseline to the end of the 3-week intervention period of bone biomarkers (P1NP, CTX)	3 weeks
Blood levels of Oxidized LDL	Change from baseline to the end of the 3-week intervention period of Oxidized LDL	3 weeks
Levels of biomarkers of oxidative stress	8-NO2GU, 8-OH-GU, 8-OH GUO, 8-OH-DGUO, 8 NO2 GUO, cGMP, 8-NO2-cGMP, Prostanoids, Oxylipins, Isoprostanes, Phytoprostanes and Phytofuranes	3 weeks

Collaborators and Investigators

• Sponsor: Nestlé
• Investigators: Principal Investigator: Francisco A. Tomás-Barberán, Prof., CEBAS-CSIC, Murcia, Spain

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2020
• Primary Completion (Actual): May 15, 2021
• Study Completion (Actual): September 15, 2021

Study Registration Dates

• First Submitted: March 5, 2020
• First Submitted That Met QC Criteria: March 30, 2020
• First Posted (Actual): March 31, 2020

Study Record Updates

• Last Update Posted (Actual): October 1, 2021
• Last Update Submitted That Met QC Criteria: September 30, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 1907NRC

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