Vascular Effects of Triglyceride-rich Lipoproteins

Not Applicable

Completed

• Conditions: Vascular Resistance; Postprandial Period; Lipemia; Vasodilation; Nitric Oxide
• Interventions: Dietary Supplement: High-fat meals varying in their fatty acid composition

• Registration Number: NCT01618071
• Lead Sponsor: King's College London

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-06
• Study First Submitted: 2012-06-08
• Study First Submitted QC: 2012-06-11
• Study First Posted: 2012-06-13
• Primary Completion: 2012-10
• Study Completion: 2012-10
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-12
• Last Update Posted: 2019-09-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 16

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Eicosapentaenoic acid and docosahexaenoic acid	High-fat meals varying in their fatty acid composition	5 g EPA and DHA derived from fish oil, made up to a total of 75 g with high oleic sunflower oil.
Linoleic acid	High-fat meals varying in their fatty acid composition	75 g high linoleic acid sunflower oil.
Docosahexaenoic acid	High-fat meals varying in their fatty acid composition	5 g DHA derived from algal oil, made up to a total of 75 g with high oleic sunflower oil.
Oleic acid	High-fat meals varying in their fatty acid composition	75 g high oleic acid sunflower oil.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Change in plasma 8-isoprostane F2alpha concentrations	0, 2, 4 and 6 h 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
Change in digital volume pulse stiffness index	0, 2, 4 and 6 h post-meal
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 cholesterol	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 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
Change in plasma nitrite/nitrate concentrations	0, 2, 4 and 6 h
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 plasma concentration versus time curve (iAUC) of triacylglycerol	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 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
Change in digital volume pulse reflection index	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

Trial Locations

Locations (1)

Diabetes & Nutritional Sciences Division, King's College London; 🇬🇧 London, United Kingdom