Impact of Extra Virgin Olive Oil Oleocanthal Content on Platelet Reactivity

• ClinicalTrials.gov Identifier: NCT02902913
• Recruitment Status: Completed
• First Posted: September 16, 2016
• Results First Posted: November 7, 2019
• Last Update Posted: April 27, 2021
• Sponsor: University of California, Davis
• Collaborator: USDA, Western Human Nutrition Research Center
• Information provided by (Responsible Party): University of California, Davis

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	Not Applicable

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 (Clinical Trial)
• 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: January 2015
• Actual Primary Completion Date: September 2015
• Actual Study Completion Date: September 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 Name: 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 Name: 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 Name: Control EVOO
Active Comparator: Ibuprofen; Ibuprofen, 400 mg	Drug: Ibuprofen; 400 mg of Ibuprofen

Outcome Measures

Primary Outcome Measures :

1. Optical Platelet Aggregometry [ Time Frame: 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 [ Time Frame: 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

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

Criteria

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

Sponsors and Collaborators

University of California, Davis

USDA, Western Human Nutrition Research Center

Investigators

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

More Information

Additional Information:

manuscript 

Publications of Results:

Agrawal K, Melliou E, Li X, Pedersen TL, Wang SC, Magiatis P, Newman JW, Holt RR. Oleocanthal-rich extra virgin olive oil demonstrates acute anti-platelet effects in healthy men in a randomized trial. J Funct Foods. 2017 Sep;36:84-93. doi: 10.1016/j.jff.2017.06.046. Epub 2017 Jul 3.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT02902913
• Other Study ID Numbers: 617247
• First Posted: September 16, 2016
• Results First Posted: November 7, 2019
• Last Update Posted: April 27, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• 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; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action