Acute Assessment of Platelet Reactivity After the Intake of Oleocanthal

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.

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