Impact of Extra Virgin Olive Oil Oleocanthal Content on Platelet Reactivity

• Sponsor: University of California, Davis (Other)
• Overall Status: Completed
• CT.gov ID: NCT02902913
• Collaborator: USDA, Western Human Nutrition Research Center (U.S. Fed)
• Enrollment: 9
• Arms: 4
• Duration (Months): 8

Study Details

Study Description

Brief Summary

Data from limited dietary intervention trials suggest that the cardiovascular health benefit of extra virgin olive oil (EVOO) may increase with phenolic content. However, while EVOOs contain an array of bioactive compounds, little information exists regarding the physiological effects of specific chemical species. Among the EVOO-derived phenolics with demonstrated anti-inflammatory effects in animal and in vitro models is oleocanthal, an inhibitor of cyclooxygenase (COX). The current study compared the impact of acute intake (40 mL) of EVOO on platelet reactivity in healthy adult males (n=9). The volunteers were randomly assigned to consume three EVOOs in a double-blind controlled trial. The EVOO were characterized and chosen for equivalency in their total phenolic content and fatty acid profiles, but differing in their oleocanthal to oleacein ratio.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Diseases	Other: D2i2; Other: D2i0.5; Other: D2i0; Drug: Ibuprofen	N/A

Detailed Description

Ten healthy adult males (20-50 years of age) will be enrolled into a randomized triple-blind, controlled crossover study that will test the acute effects of oleocanthal-rich extra virgin olive oil intake on platelet aggregation. Each participant will be asked to participate in four study days, separated by at least 1-week, in which they will be randomized to consume on each study day 40 mL (~3 tablespoons) of either oleocanthal-rich extra virgin olive oil (OO), or an extra virgin OO that is matched in total phenolics but oleocanthal-poor, or a refined OO that is low in all phenolics In addition to the oils, on a fourth study day visit, after completion of the study visits involving oil intake the subjects will be asked to take 400mg of ibuprofen.

Collection procedures will be performed at the same time of the day to avoid circadian effects. A blood sample (50 mL ~ 3.5 tbsp) will be collected for the measurement of platelet aggregometry and COX metabolites. Following this initial blood draw, the subjects will consume their assigned test product for the day. Two-hours following the intake of the assigned olive oil, a second blood sample will be drawn (50 mL ~ 3.5 tbsp). After the second blood draw, the study day will be complete.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: All participants received all four interventions in a randomized, cross-over design in which both participant and caregiver were masked to the assignment (with the exception of the fourth intervention, ibuprofen, which was always administered at the final study visit).
• Primary Purpose: Prevention
• Official Title: Impact of Extra Virgin Olive Oil Oleocanthal Content on Platelet Reactivity in Healthy Humans
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oleocanthal-rich, D2i2 Oleocanthal-rich, D2i2 (Extra virgin olive oil containing oleocanthal to oleacein in a 2:1 ratio)	Other: D2i2; Oleocanthal provided in a 2:1 ratio compared to oleacein; Other Names: Oleocanthal-rich
Experimental: Oleacein-rich, D2i0.5 Oleacein-rich, D2i0.5 (Extra virgin olive oil containing oleocanthal to oleacein in a 1:2 ratio)	Other: D2i0.5; Oleocanthal provided in a 1:2 ratio compared to oleacein; Other Names: Oleocanthal-low
Placebo Comparator: Oleocanthal and Oleacein-low, D2i0 Oleocanthal and Oleacein-low, D2i0 (Extra virgin olive oil containing low amounts of oleocanthal to oleacein, but with a similar total phenolic content as the other two oils)	Other: D2i0; No oleocanthal and no oleacein; Other Names: Control EVOO
Active Comparator: Ibuprofen Ibuprofen, 400 mg	Drug: Ibuprofen; 400 mg of Ibuprofen

Outcome Measures

Primary Outcome Measures

1. Optical Platelet Aggregometry [Change from baseline 2 hours post intake]

   Maximal platelet aggregation in minutes will be measured using optical platelet aggregometry

Secondary Outcome Measures

1. Activated Platelet Oxylipin Production [Change from baseline 2 hours post intake]

   Oxylipins derived from cyclooxygenase, lipoxygenase, and cytochrome P450 dependent metabolism of AA were quantified using liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 100 µL of PRP plasma activated with collagen or ADP as well as 100 µL of unactivated PRP plasma collected before and two hours after treatment with EVOO or ibuprofen. Data were mean centered and reported as a % change from baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 50 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Willing and able to comply with study protocols

• Willing to drink 2 tablespoons of olive oil

• BMI 18.5 to 30 kg/m2

• Weight ≥ 110 pounds

Exclusion Criteria:

• Adults who are not able to consent

• BMI ≥ 31 kg/m2

• Under current medical supervision

• Self-reported daily use of drugs that are known to affect platelet function, such as aspirin, Excedrin, and NSAIDS

• Ibuprofen intolerance or allergy

• Cannot speak English

• Allergy to olives or olive oil

• Vegetarian, Vegan, food faddists, individuals using non-traditional diets, on a weight loss diet or individual following diets with significant deviations from the average diet of the general population.

• A history of cardiovascular disease, stroke, cancer, renal, hepatic, or thyroid disease, GI tract disorders, previous GI surgery

• Currently taking prescription drugs or supplements

• Indications of substance or alcohol abuse within the last 3 years

• Not willing to stop any supplement use, including herbal, plant or botanical, fish oil, oil supplements.

• Not willing to refrain from olive oil consumption.

• Blood Pressure ≥ 140/90 mmHg

• Self-reported malabsorption

• Metabolic panel results or complete blood counts that are outside of the normal reference range.

• Screening LDL ≥ 190 mg/dl for those who have 0 - 1 major risk factors apart from LDL cholesterol [(i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL].

• Screening LDL ≥ 160 mg/dl for those who have 2 major risk factors apart from LDL cholesterol [(i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL].

• Screening LDL ≥ than 130 mg/dl for those who have 2 major risk factors apart from LDL cholesterol ((i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL), and a Framingham 10 - year Risk Score 10 - 20 % (using NCEP calculator).

• Current enrollee in a clinical research study.

• Individuals with blood clotting or platelet defect disorders

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• University of California, Davis
• USDA, Western Human Nutrition Research Center

Investigators

• Principal Investigator: Roberta R Holt, PhD, University of California, Davis

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• manuscript

Publications

None provided.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT02902913
• Other Study ID Numbers: 617247
• First Posted: Sep 16, 2016
• Last Update Posted: Apr 27, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of California, Davis: platelet reactivity; phenolic; extra virgin olive oil; cyclooxygenase; oleocanthal; oxylipin
• Additional relevant MeSH terms: Cardiovascular Diseases; Ibuprofen

Study Results

Participant Flow

Arm/Group Title	All Participants
Arm/Group Description	All participants received all four study interventions. The first three interventions were administered in random order: Oleocanthal-rich, D2i2 Oleacein-rich, D2i0.5 Oleocanthal and Oleacein-low, D2i0 All participants received the last intervention, 400 mg of Ibuprofen, at the fourth (final) study visit.
Period Title: Overall Study
STARTED	9
First Intervention (1 Day)	9
Washout (7 Days)	9
Second Intervention (1 Day)	9
Washout (7 Days)	9
Third Intervention (1 Day)	9
Washout (7 Days)	9
Ibuprofen (400mg)	9
COMPLETED	9
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	All participants received all four study interventions. The first three interventions were administered in random order: Oleocanthal-rich, D2i2 Oleacein-rich, D2i0.5 Oleocanthal and Oleacein-low, D2i0 All participants received the last intervention, 400 mg of Ibuprofen, at the fourth (final) study visit.
Overall Participants	9
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26 (4)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	9 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 11.1%
Not Hispanic or Latino	8 88.9%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	9 100%

Outcome Measures

1. Primary Outcome

Title	Optical Platelet Aggregometry
Description	Maximal platelet aggregation in minutes will be measured using optical platelet aggregometry
Time Frame	Change from baseline 2 hours post intake

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants
Arm/Group Description	All participants received all four study interventions. The first three interventions were administered in random order: Oleocanthal-rich, D2i2 Oleacein-rich, D2i0.5 Oleocanthal and Oleacein-low, D2i0 All participants received the last intervention, 400 mg of Ibuprofen, at the fourth (final) study visit.
Measure Participants	9
D2i2	-13 (36)
D2i0.5	-35 (39)
D2i0	7 (24)
Ibuprofen	-57.5 (32.9)

2. Secondary Outcome

Title	Activated Platelet Oxylipin Production
Description	Oxylipins derived from cyclooxygenase, lipoxygenase, and cytochrome P450 dependent metabolism of AA were quantified using liquid chromatography with tandem mass spectrometry (LC-MS/MS) in 100 µL of PRP plasma activated with collagen or ADP as well as 100 µL of unactivated PRP plasma collected before and two hours after treatment with EVOO or ibuprofen. Data were mean centered and reported as a % change from baseline.
Time Frame	Change from baseline 2 hours post intake

Outcome Measure Data

Analysis Population Description

healthy adult males

Arm/Group Title	Oleocanthal-rich, D2i2	Oleacein-rich, D2i0.5	Oleocanthal and Oleacein-low, D2i0	Ibuprofen
Arm/Group Description	Oleocanthal-rich, D2i2 (Extra virgin olive oil containing oleocanthal to oleacein in a 2:1 ratio) D2i2: Oleocanthal provided in a 2:1 ratio compared to oleacein	Oleacein-rich, D2i0.5 (Extra virgin olive oil containing oleocanthal to oleacein in a 1:2 ratio) D2i0.5: Oleocanthal provided in a 1:2 ratio compared to oleacein	Oleocanthal and Oleacein-low, D2i0 (Extra virgin olive oil containing low amounts of oleocanthal to oleacein, but with a similar total phenolic content as the other two oils) D2i0: No oleocanthal and no oleacein	Ibuprofen, 400 mg Ibuprofen: 400 mg of Ibuprofen
Measure Participants	9	9	9	9
Number [percentage of change from baseline]	-0.02	-0.45	-0.17	-0.66

Adverse Events

Arm/Group Title	All Participants
Arm/Group Description	All participants received all four study interventions. The first three interventions were administered in random order: Oleocanthal-rich, D2i2 Oleacein-rich, D2i0.5 Oleocanthal and Oleacein-low, D2i0 All participants received the last intervention, 400 mg of Ibuprofen, at the fourth (final) study visit.
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	0/9 (0%)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	0/9 (0%)
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.