Lipemia, Nitric Oxide, Postprandial Period, Vascular Resistance, Vasodilation
Conditions
Keywords
n-3 PUFA, Endothelial cells, Nitric oxide, Oxidative stress, Blood pressure, Vasodilation, Lipemia, Unsaturated dietary fats
Brief summary
Many types of cardiovascular disease begin when the layer of cells lining blood vessels (endothelial cells) start to function abnormally. This causes white blood cells (monocytes) to enter the blood vessel wall and eventually form lesions. Fats from foods we consume are carried in the blood for 3-8 hours after a fatty meal in small particles known as chylomicrons (CM) and chylomicron remnants (CMR). The overall aim of this project is to investigate the idea that n-3 polyunsaturated fatty acids (PUFA) protect against heart disease by modifying the effect of CMR on endothelial cells and monocytes. We hypothesize that n3-PUFA carried in CMR reduce detrimental events which promote blood vessel damage and activate protective mechanisms to improve the function of arteries.
Interventions
DIETARY_SUPPLEMENTHigh-fat meals varying in their fatty acid composition
70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements
Sponsors
Royal Veterinary College
King's College London
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
35 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males * Non-smokers * Aged 35-70 years * Fasting TAG concentrations ≥1.2 mmol/L.
Exclusion criteria
* Reported history of CVD (myocardial infarction, angina, venous thrombosis, stroke), impaired fasting glucose/uncontrolled type 2 diabetes (or fasting glucose ≥ 6.1 mmol/L), cancer, kidney, liver or bowel disease. * Presence of gastrointestinal disorder or use of drug, which is likely to alter gastrointestinal motility or nutrient absorption. * History of substance abuse or alcoholism (previous weekly alcohol intake \>60 units/men) * Current self-reported weekly alcohol intake exceeding 28 units * Allergy or intolerance to any component of test meals * Unwilling to restrict consumption of any source of fish oil for the length of the study * Weight change of \>3kg in preceding 2 months * Body Mass Index \<20 and \>35 kg/m2 * Fasting blood cholesterol \> 7.8 mmol/L * Current cigarette smoker. * Current use of lipid lowering medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 6 h postprandial chylomicron remnant-rich lipoprotein fraction | 6 h post-meal | The primary outcome of the study is activation of inflammatory/oxidative stress pathways within cultured endothelial cells following incubation with pooled postprandial lipoprotein fractions rich in chylomicron remnants. Due to the nature of this type of research this necessitates more than one primary outcome measure: the primary measures are NF-kappa-beta activation, cytokine production (e.g. interleukin-6) and reactive oxygen species generation in the cultured human endothelial cells. |
Secondary
| Measure | Time frame |
|---|---|
| Incremental area under the plasma concentration versus time curve (iAUC) of glucose | 0, 1, 2, 3, 4, 5 and 6 h post-meal |
| Incremental area under the plasma concentration versus time curve (iAUC) for non-esterified fatty acids | 0, 1, 2, 3, 4, 5 and 6 h post-meal |
| Incremental area under the plasma concentration versus time curve (iAUC) for plasma fatty acid composition (%) | 0, 1, 2, 3, 4, 5 and 6 h post-meal |
| Incremental area under the plasma concentration versus time curve (iAUC) for cholesterol | 0, 1, 2, 3, 4, 5 and 6 h post-meal |
| Incremental area under the unit measure versus time curve for brachial augmentation index | 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal |
| Incremental area under the unit measure versus time curve for systolic blood pressure | 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal |
| Incremental area under the plasma concentration versus time curve (iAUC) of triacylglycerol | 0, 1, 2, 3, 4, 5 and 6 h post-meal |
| Change in digital volume pulse stiffness index | 0, 2, 4 and 6 h post-meal |
| Change in digital volume pulse reflection index | 0, 2, 4 and 6 h post-meal |
| Change in plasma nitrite/nitrate concentrations | 0, 2, 4 and 6 h |
| Change in plasma 8-isoprostane F2alpha concentrations | 0, 2, 4 and 6 h post-meal |
| Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 4 h postprandial chylomicron remnant-rich lipoprotein fraction | 4 h post-meal |
| Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 5 h postprandial chylomicron remnant-rich lipoprotein fraction | 5 h post-meal |
| Incremental area under the unit measure versus time curve for diastolic blood pressure | 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal |
Countries
United Kingdom
Outcome results
None listed