Acute Assessment of Platelet Reactivity After the Intake of Oleocanthal

Study Overview
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Brief Summary
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The investigators have previously observed a reduced level of platelet aggregation 2 hours after healthy male individuals were asked to drink extra virgin olive oil (EVOO) that provided a higher level of one specific phenolic known as oleocanthal. This study will help the investigators further determine the effects of oleocanthal-rich EVOO intake on platelet function at 2, 4 and 6 hours after intake with food compared to platelet function in the morning after an overnight fast.

Detailed Description
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Fifty adult male volunteers will be asked to participate in one of two study trials that will be randomized double-blind controlled crossover trials with 2 study visits. The participants will arrive to the facility after an overnight fast, and will be asked to consume their assigned EVOO either without (trial 1) or with (trial 2) a standardized low-phenolic food (such as rice, pasta or mashed potatoes) with 40 mL of one of 2 EVOOs that are matched for their total phenolic content, but with one oil containing oleocanthal, and one with very low levels of oleocanthal. At zero, two, 4 and 6 hours after EVOO intake a blood sample will be collected for the assessment of collagen- ADP-, and AA-induced platelet aggregation, as well as an untargeted metabolomics profile. As an assessment of phenotypic stability, a subset of individuals (n=5 per trial) that have exhibit either low or high platelet responses, will be asked to repeat the above study.

Official Title
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Acute Assessment of Platelet Reactivity After the Intake of Oleocanthal From Extra Virgin Olive Oil in the Fasted and Fed Condition

Conditions
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Platelet Aggregation, Nutritional and Metabolic Disease, Cardiovascular Diseases

Intervention / Treatment
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* Other: Oleocanthal-Rich Extra Virgin Olive Oil
* Other: Oleocanthal-low Extra Virgin Olive Oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Trials 1 and 2: Male; Trial 3: Male and Female 20-45 years old For females, a regular 25-30-day menstrual cycle Subject is willing and able to comply with the study protocols Subject is willing to drink 40 mL (approximately 2 tablespoons) of olive oil BMI 18.5 - 30 kg/m2 Weight ≥ 110 pounds Exclusion Criteria: Adults who are not able to consent BMI ≥ 31 kg/m2 Under current medical supervision 1 ug/ml and 3 ug/ml collagen screening maximal platelet aggregatory response of < 65%. Platelet number or mean platelet values that are outside of the normal reference range as indicated on a complete blood cell count report from the UCD Med Center Current diagnosis of anemia; or a screening hemoglobin and hematocrit that is less than the normal reference range. Self-reported daily use of drugs that are known to affect platelet function, such as aspirin, Excedrin, and NSAIDS Females using hormonal contraception Ibuprofen intolerance or allergy Those with a bleeding disorder Non-English speaking Allergy to olives or olive oil Vegetarian, Vegan, food faddists, individuals using non-traditional diets, or on a weight loss diet. 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 for six weeks prior to study enrollment. Not willing to refrain from olive oil consumption for 4 weeks prior to study enrollment, and throughout study enrollment Self-reported malabsorption (e.g. difficulty digesting or absorbing nutrients from food, potentially leading to bloating, cramping or gas) Current enrollee in a clinical research study. Individuals with blood clotting or platelet defect disorders

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: controlled, randomized, double-blind, with 2 interventions
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oleocanthal-Rich Extra Virgin Olive Oil<br>Extra Virgin Olive Oil that is high in the phenolic oleocanthal, but contains similar amounts of total phenolics as the Oleocanthal-Low Extra Virgin Olive Oil | Other: Oleocanthal-Rich Extra Virgin Olive Oil<br>* Extra Virgin Olive Oil that contains a high level of the phenolic oleocanthal<br>Other: Oleocanthal-low Extra Virgin Olive Oil<br>* Extra Virgin Olive Oil that contains a low level of the phenolic oleocanthal<br>|
| Placebo Comparator: Oleocanthal-Low Extra Virgin Olive Oil<br>Extra Virgin Olive Oil that is low in the phenolic oleocanthal, but contains similar amounts of total phenolics as the Oleocanthal-Rich Extra Virgin Olive Oil | Other: Oleocanthal-Rich Extra Virgin Olive Oil<br>* Extra Virgin Olive Oil that contains a high level of the phenolic oleocanthal<br>Other: Oleocanthal-low Extra Virgin Olive Oil<br>* Extra Virgin Olive Oil that contains a low level of the phenolic oleocanthal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Influence of Oleocanthal-rich EVOO intake on Collagen-induced platelet aggregometry | Optical platelet aggregometry will be used to measure platelet aggregation. The percent maximal platelet aggregation will be measured. A reduction in maximal aggregation 2, 4 or 6 hours post EVOO intake compared to baseline will represent a reduction in platelet aggregation. | baseline, 2, 4 and 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Influence of Oleocanthal-rich EVOO intake on Adenosine Diphosphate-induced platelet aggregometry | Optical platelet aggregometry will be used to measure platelet aggregation. The percent maximal platelet aggregation will be measured. A reduction in maximal aggregation 2, 4 or 6 hours post EVOO intake compared to baseline will represent a reduction in platelet aggregation. | baseline, 2, 4 and 6 hours | 
| Influence of Oleocanthal-rich EVOO intake on Arachidonic Acid-induced platelet aggregometry | Optical platelet aggregometry will be used to measure platelet aggregation. The percent maximal platelet aggregation will be measured. A reduction in maximal aggregation 2, 4 or 6 hours post EVOO intake compared to baseline will represent a reduction in platelet aggregation. | baseline, 2, 4 and 6 hours | 
| Influence of Oleocanthal-rich EVOO intake on Platelet-derived oxylipins | Oxylipin profile will be conducted from the activated platelet supernatant ultra high-performance liquid chromatography-mass spectrometry (HPLC) is used to measure levels of oxylipin. HPLC area under the peak will be measured. | baseline, 2, 4 and 6 hours | 
| Influence of Oleocanthal-rich EVOO intake on Metabolomics | Untargeted metabolomics will be performed to assess the relationship between platelet response and the presence of circulating plasma metabolites. | baseline, 2, 4 and 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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platelet, aggregation, phenolic, olive oil, oleocanthal