Healthy
Conditions
Keywords
Oats, Phenolic acid, FMD, LDI, Avenanthramide
Brief summary
In this proposed human trial, the investigators aim to establish whether consumption of one portion of phenolic acid-rich oats leads to acute improvements (i.e. 1-24h post-intake) in markers of cardiovascular disease risk relative to an energy matched control intervention in healthy men with high-normal to mildly elevated blood pressure.
Detailed description
A diet rich in whole grain is inversely associated with cardiovascular disease risk. Whole grains contain a wide range dietary components including potentially vasoactive phenolic acids.
Interventions
OTHEROat
The study oat intervention products will consist of 67.7g oatflake and 22.5g oatbran concentrate.
OTHERControl
60g cream of rice
Sponsors
Biotechnology and Biological Sciences Research Council
Rothamsted Research
PepsiCo Global R&D
University of Roehampton
University of Reading
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
25 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Above average blood pressure (i.e. systolic 120-159 mmHg and diastolic 75-99 mmHg)
Exclusion criteria
* Abnormal biochemical, haematological results as assessed at health screening * Hypertension (i.e. systolic/diastolic blood pressure ≥160/100 mm Hg) BMI \>35 * Current smoker or ex-smoker ceasing \<3 months ago * Past or existing medical history of vascular disease, diabetes, hepatic, renal, gastrointestinal, haematological, neurological, thyroidal disease or cancer * Prescribed or taking lipid lowering, antihypertensive, vasoactive (e.g. Viagra), anti-inflammatory, antibiotic or antidepressant medication * Allergies to whole grains * Parallel participation in another research project * Having flu vaccination or antibiotics within 3 months of trial start * On a weight reduction regime or taking food supplements within 3 months of trial start * Performing high level of physical activity (i.e. \>3 x 20 min aerobic exercise/week) * Consumption of ≥21 units of alcohol/week * Small veins not allowing cannulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flow Mediated Dilatation | 1 hour, 6 hours and 24 hours | Technique to assess the flexibility of the endothelium in larger peripheral blood vessels |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phenolic Acids Metabolites - Ferulic Acid | Baseline, 1hour, 2 hours and 24hours | Concentration of phenolic acid metabolites in plasma and urine as Assessed by liquid chromatography/mass spectrometry magnitude of increase from Baseline to 24h |
| Plasma Nitric Oxide Analysis | Acute postprandial timecourse from Baseline, 1hour to 24hours. | Concentration of nitric oxide in nmol |
| NADPH Oxidase Activity in Neutrophil Blood Cells | Baseline, 2 hours and 24 hours | NADPH oxidase activity will be calculated as the difference between values obtained in PMA The fluorescence intensity was measured by C6 Flow Cytometer |
| Laser Doppler Iontophoresis | Baseline(BL), 2hours and 24hours | Acute postprandial timecourse from Baseline to 2 hours, 24hours, AUC - area under the blood flow and time curve Ach-iAUC-endothelium dependent incremental area under the curve SNP-iAUC-endothelium independent incremental area under the curve Ach-AUC- endothelium dependent area under the curve |
| Plasma Insulin | Acute postprandial timecourse from Baseline, 1hour to 24hours. | Insulin concentration in pmol/L |
| Renin Activity | Acute postprandial timecourse from Baseline, 1hour to 24hours. | Renin activity in ng/(mL\*hour) |
| Plasma Glucose | Acute postprandial timecourse from Baseline, 1hour to 24hours. | Glucose concentration in mmol/L |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participant Crossover study - All participant | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | All Participant |
|---|---|
| Age, Continuous | 47 years STANDARD_DEVIATION 4 |
| Diastolic blood pressure | 81.1 mmHg STANDARD_DEVIATION 1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Region of Enrollment United Kingdom | 16 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 16 Participants |
| Systolic blood pressure | 133.9 mmHg STANDARD_DEVIATION 2.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 1 / 18 | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
Flow Mediated Dilatation
Technique to assess the flexibility of the endothelium in larger peripheral blood vessels
Time frame: 1 hour, 6 hours and 24 hours
Population: Excluded data from 2 volunteers as their results were out of the normal range
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oat Intervention | Flow Mediated Dilatation | 1h | 4.4 metre | Standard Error 0.7 |
| Oat Intervention | Flow Mediated Dilatation | 6h | 3.4 metre | Standard Error 0.6 |
| Oat Intervention | Flow Mediated Dilatation | 24h | 4.4 metre | Standard Error 0.4 |
| Control | Flow Mediated Dilatation | 24h | 3.6 metre | Standard Error 0.7 |
| Control | Flow Mediated Dilatation | 1h | 3.9 metre | Standard Error 0.9 |
| Control | Flow Mediated Dilatation | 6h | 4.4 metre | Standard Error 0.8 |
Comparison: Between time points and treatments, calculated p valuep-value: 0.5Mixed Models Analysis
Secondary
Laser Doppler Iontophoresis
Acute postprandial timecourse from Baseline to 2 hours, 24hours, AUC - area under the blood flow and time curve Ach-iAUC-endothelium dependent incremental area under the curve SNP-iAUC-endothelium independent incremental area under the curve Ach-AUC- endothelium dependent area under the curve
Time frame: Baseline(BL), 2hours and 24hours
Population: Excluded data from 2 volunteers as their results were out of the normal range
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oat Intervention | Laser Doppler Iontophoresis | Ach-i AUC, 24h | 381.3 PU per hour | Standard Error 61.4 |
| Oat Intervention | Laser Doppler Iontophoresis | SNP-iAUC,24h | 622.4 PU per hour | Standard Error 50.6 |
| Oat Intervention | Laser Doppler Iontophoresis | Ach-i AUC, BL | 538.2 PU per hour | Standard Error 90.4 |
| Oat Intervention | Laser Doppler Iontophoresis | Ach-AUC, BL | 1593.9 PU per hour | Standard Error 198.9 |
| Oat Intervention | Laser Doppler Iontophoresis | SNP-iAUC BL | 661.1 PU per hour | Standard Error 52.4 |
| Oat Intervention | Laser Doppler Iontophoresis | Ach-AUC, 2h | 1678.3 PU per hour | Standard Error 140.6 |
| Oat Intervention | Laser Doppler Iontophoresis | Ach-i AUC, 2h | 681.8 PU per hour | Standard Error 182 |
| Oat Intervention | Laser Doppler Iontophoresis | Ach-AUC, 24h | 1560.9 PU per hour | Standard Error 161.3 |
| Oat Intervention | Laser Doppler Iontophoresis | SNP-iAUC 2h | 709.4 PU per hour | Standard Error 68.4 |
| Control | Laser Doppler Iontophoresis | Ach-AUC, 24h | 1701.6 PU per hour | Standard Error 190.9 |
| Control | Laser Doppler Iontophoresis | Ach-i AUC, 2h | 463.7 PU per hour | Standard Error 55.4 |
| Control | Laser Doppler Iontophoresis | Ach-i AUC, 24h | 315 PU per hour | Standard Error 45.5 |
| Control | Laser Doppler Iontophoresis | SNP-iAUC BL | 757.1 PU per hour | Standard Error 43.2 |
| Control | Laser Doppler Iontophoresis | SNP-iAUC 2h | 502.9 PU per hour | Standard Error 25.6 |
| Control | Laser Doppler Iontophoresis | SNP-iAUC,24h | 513.7 PU per hour | Standard Error 35.8 |
| Control | Laser Doppler Iontophoresis | Ach-AUC, BL | 1534.1 PU per hour | Standard Error 144.2 |
| Control | Laser Doppler Iontophoresis | Ach-AUC, 2h | 1358.3 PU per hour | Standard Error 116.9 |
| Control | Laser Doppler Iontophoresis | Ach-i AUC, BL | 465 PU per hour | Standard Error 70.6 |
Comparison: Ach-iAUCp-value: 0.04Mixed Models Analysis
Comparison: SNP-IAUCp-value: 0.007Mixed Models Analysis
Comparison: Ach - AUCp-value: 0.02Mixed Models Analysis
Secondary
NADPH Oxidase Activity in Neutrophil Blood Cells
NADPH oxidase activity will be calculated as the difference between values obtained in PMA The fluorescence intensity was measured by C6 Flow Cytometer
Time frame: Baseline, 2 hours and 24 hours
Population: Excluded data from 2 volunteers as their results were out of the normal range
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oat Intervention | NADPH Oxidase Activity in Neutrophil Blood Cells | BL | 55.7 fluorescence intensity | Standard Error 7 |
| Oat Intervention | NADPH Oxidase Activity in Neutrophil Blood Cells | 2h | 43.6 fluorescence intensity | Standard Error 5 |
| Oat Intervention | NADPH Oxidase Activity in Neutrophil Blood Cells | 24h | 63.6 fluorescence intensity | Standard Error 6 |
| Control | NADPH Oxidase Activity in Neutrophil Blood Cells | BL | 58.6 fluorescence intensity | Standard Error 8 |
| Control | NADPH Oxidase Activity in Neutrophil Blood Cells | 2h | 47.9 fluorescence intensity | Standard Error 8 |
| Control | NADPH Oxidase Activity in Neutrophil Blood Cells | 24h | 61.6 fluorescence intensity | Standard Error 9 |
p-value: 0.7Mixed Models Analysis
Secondary
Phenolic Acids Metabolites - Ferulic Acid
Concentration of phenolic acid metabolites in plasma and urine as Assessed by liquid chromatography/mass spectrometry magnitude of increase from Baseline to 24h
Time frame: Baseline, 1hour, 2 hours and 24hours
Population: Excluded data from 2 volunteers as their results were out of the normal range
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oat Intervention | Phenolic Acids Metabolites - Ferulic Acid | BL | 10.6 nanomolars | Standard Deviation 7.8 |
| Oat Intervention | Phenolic Acids Metabolites - Ferulic Acid | 1h | 33.9 nanomolars | Standard Deviation 17.5 |
| Oat Intervention | Phenolic Acids Metabolites - Ferulic Acid | 2h | 153.5 nanomolars | Standard Deviation 145.2 |
| Oat Intervention | Phenolic Acids Metabolites - Ferulic Acid | 24h | 373 nanomolars | Standard Deviation 4 |
| Control | Phenolic Acids Metabolites - Ferulic Acid | 24h | 222 nanomolars | Standard Deviation 24 |
| Control | Phenolic Acids Metabolites - Ferulic Acid | BL | 0.4 nanomolars | Standard Deviation 2.4 |
| Control | Phenolic Acids Metabolites - Ferulic Acid | 2h | 10.3 nanomolars | Standard Deviation 9.3 |
| Control | Phenolic Acids Metabolites - Ferulic Acid | 1h | 9 nanomolars | Standard Deviation 6.4 |
p-value: 0.9Mixed Models Analysis
Secondary
Plasma Glucose
Glucose concentration in mmol/L
Time frame: Acute postprandial timecourse from Baseline, 1hour to 24hours.
Population: Data not collected
Secondary
Plasma Insulin
Insulin concentration in pmol/L
Time frame: Acute postprandial timecourse from Baseline, 1hour to 24hours.
Population: Data not collected
Secondary
Plasma Nitric Oxide Analysis
Concentration of nitric oxide in nmol
Time frame: Acute postprandial timecourse from Baseline, 1hour to 24hours.
Population: No data collected
Secondary
Renin Activity
Renin activity in ng/(mL\*hour)
Time frame: Acute postprandial timecourse from Baseline, 1hour to 24hours.
Population: Data not collected