Cardiovascular Diseases
Conditions
Keywords
platelet reactivity, phenolic, extra virgin olive oil, cyclooxygenase, oleocanthal, oxylipin
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.
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.
Interventions
OTHERD2i2
Oleocanthal provided in a 2:1 ratio compared to oleacein
OTHERD2i0.5
Oleocanthal provided in a 1:2 ratio compared to oleacein
OTHERD2i0
No oleocanthal and no oleacein
DRUGIbuprofen
400 mg of Ibuprofen
Sponsors
USDA, Western Human Nutrition Research Center
University of California, Davis
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, 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).
Eligibility
Sex/Gender
MALE
Age
20 Years to 50 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Optical Platelet Aggregometry | Change from baseline 2 hours post intake | Maximal platelet aggregation in minutes will be measured using optical platelet aggregometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants 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. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 26 years STANDARD_DEVIATION 4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Optical Platelet Aggregometry
Maximal platelet aggregation in minutes will be measured using optical platelet aggregometry
Time frame: Change from baseline 2 hours post intake
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Optical Platelet Aggregometry | D2i2 | -13 percentage of maximal aggregation | Standard Deviation 36 |
| All Participants | Optical Platelet Aggregometry | D2i0.5 | -35 percentage of maximal aggregation | Standard Deviation 39 |
| All Participants | Optical Platelet Aggregometry | D2i0 | 7 percentage of maximal aggregation | Standard Deviation 24 |
| All Participants | Optical Platelet Aggregometry | Ibuprofen | -57.5 percentage of maximal aggregation | Standard Deviation 32.9 |
Secondary
Activated Platelet Oxylipin Production
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
Population: healthy adult males
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Activated Platelet Oxylipin Production | -0.02 percentage of change from baseline |
| Oleacein-rich, D2i0.5 | Activated Platelet Oxylipin Production | -0.45 percentage of change from baseline |
| Oleocanthal and Oleacein-low, D2i0 | Activated Platelet Oxylipin Production | -0.17 percentage of change from baseline |
| Ibuprofen | Activated Platelet Oxylipin Production | -0.66 percentage of change from baseline |