Unravelling the Mechanisms of Vascular Protection by n3-PUFAs to Optimise and Support Their Use as Bioactives by the Food Industry
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 6 h postprandial chylomicron remnant-rich lipoprotein fraction
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 35 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy males
- •Non-smokers
- •Aged 35-70 years
- •Fasting TAG concentrations ≥1.2 mmol/L.
排除标准
- •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
研究组 & 干预措施
Oleic acid
75 g high oleic acid sunflower oil.
干预措施: High-fat meals varying in their fatty acid composition (Dietary Supplement)
Linoleic acid
75 g high linoleic acid sunflower oil.
干预措施: High-fat meals varying in their fatty acid composition (Dietary Supplement)
Eicosapentaenoic acid and docosahexaenoic acid
5 g EPA and DHA derived from fish oil, made up to a total of 75 g with high oleic sunflower oil.
干预措施: High-fat meals varying in their fatty acid composition (Dietary Supplement)
Docosahexaenoic acid
5 g DHA derived from algal oil, made up to a total of 75 g with high oleic sunflower oil.
干预措施: High-fat meals varying in their fatty acid composition (Dietary Supplement)
结局指标
主要结局
Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 6 h postprandial chylomicron remnant-rich lipoprotein fraction
时间窗: 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.
次要结局
- 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)
研究者
Dr Wendy Hall
Lecturer in Nutritional Sciences
King's College London