Vascular Effects of Triglyceride-rich Lipoproteins - Full Text View

Purpose

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.

Condition	Intervention
Postprandial Period Lipemia Vasodilation Vascular Resistance Nitric Oxide	Dietary Supplement: High-fat meals varying in their fatty acid composition

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Basic Science
Official Title:	Unravelling the Mechanisms of Vascular Protection by n3-PUFAs to Optimise and Support Their Use as Bioactives by the Food Industry

Resource links provided by NLM:

Drug Information available for: Fish oil Omega-3 Fatty Acids

U.S. FDA Resources

Further study details as provided by King's College London:

Primary Outcome Measures:

Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 6 h postprandial chylomicron remnant-rich lipoprotein fraction [ Time Frame: 6 h post-meal ] [ Designated as safety issue: No ]
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:

Incremental area under the plasma concentration versus time curve (iAUC) of triacylglycerol [ Time Frame: 0, 1, 2, 3, 4, 5 and 6 h post-meal ] [ Designated as safety issue: No ]
Incremental area under the plasma concentration versus time curve (iAUC) of glucose [ Time Frame: 0, 1, 2, 3, 4, 5 and 6 h post-meal ] [ Designated as safety issue: No ]
Incremental area under the plasma concentration versus time curve (iAUC) for non-esterified fatty acids [ Time Frame: 0, 1, 2, 3, 4, 5 and 6 h post-meal ] [ Designated as safety issue: No ]
Incremental area under the plasma concentration versus time curve (iAUC) for plasma fatty acid composition (%) [ Time Frame: 0, 1, 2, 3, 4, 5 and 6 h post-meal ] [ Designated as safety issue: No ]
Incremental area under the plasma concentration versus time curve (iAUC) for cholesterol [ Time Frame: 0, 1, 2, 3, 4, 5 and 6 h post-meal ] [ Designated as safety issue: No ]
Incremental area under the unit measure versus time curve for brachial augmentation index [ Time Frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal ] [ Designated as safety issue: No ]
Incremental area under the unit measure versus time curve for systolic blood pressure [ Time Frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal ] [ Designated as safety issue: No ]
Incremental area under the unit measure versus time curve for diastolic blood pressure [ Time Frame: 0, 30, 60, 90, 120, 150, 180, 210, 240, 270, 300, 330 and 360 min post-meal ] [ Designated as safety issue: No ]
Change in digital volume pulse stiffness index [ Time Frame: 0, 2, 4 and 6 h post-meal ] [ Designated as safety issue: No ]
Change in digital volume pulse reflection index [ Time Frame: 0, 2, 4 and 6 h post-meal ] [ Designated as safety issue: No ]
Change in plasma nitrite/nitrate concentrations [ Time Frame: 0, 2, 4 and 6 h ] [ Designated as safety issue: No ]
Change in plasma 8-isoprostane F2alpha concentrations [ Time Frame: 0, 2, 4 and 6 h post-meal ] [ Designated as safety issue: No ]
Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 4 h postprandial chylomicron remnant-rich lipoprotein fraction [ Time Frame: 4 h post-meal ] [ Designated as safety issue: No ]
Activation of inflammatory/oxidative stress pathways within cultured endothelial cells following treatment with 5 h postprandial chylomicron remnant-rich lipoprotein fraction [ Time Frame: 5 h post-meal ] [ Designated as safety issue: No ]

Estimated Enrollment:	16
Study Start Date:	June 2012
Study Completion Date:	October 2012
Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Oleic acid 75 g high oleic acid sunflower oil.	Dietary Supplement: High-fat meals varying in their fatty acid composition 70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements Other Names: DHASCO Purified fish oil
Active Comparator: Linoleic acid 75 g high linoleic acid sunflower oil.	Dietary Supplement: High-fat meals varying in their fatty acid composition 70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements Other Names: DHASCO Purified fish oil
Experimental: 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.	Dietary Supplement: High-fat meals varying in their fatty acid composition 70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements Other Names: DHASCO Purified fish oil
Experimental: Docosahexaenoic acid 5 g DHA derived from algal oil, made up to a total of 75 g with high oleic sunflower oil.	Dietary Supplement: High-fat meals varying in their fatty acid composition 70 g fat incorporated into a muffin and milkshake meal, consumed following fasting baseline measurements Other Names: DHASCO Purified fish oil

Eligibility

Ages Eligible for Study:	35 Years to 70 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01618071

Locations

United Kingdom
Diabetes & Nutritional Sciences Division, King's College London
London, United Kingdom, SE1 9NH

Sponsors and Collaborators

King's College London

Royal Veterinary College

Investigators

Principal Investigator:

Wendy L Hall, PhD

King's College London

More Information

Publications:

Lambert MS, Botham KM, Mayes PA. Modification of the fatty acid composition of dietary oils and fats on incorporation into chylomicrons and chylomicron remnants. Br J Nutr. 1996 Sep;76(3):435-45.

Botham KM, Bravo E, Elliott J, Wheeler-Jones CP. Direct interaction of dietary lipids carried in chylomicron remnants with cells of the artery wall: implications for atherosclerosis development. Curr Pharm Des. 2005;11(28):3681-95. Review.

Proctor SD, Vine DF, Mamo JC. Arterial retention of apolipoprotein B(48)- and B(100)-containing lipoproteins in atherogenesis. Curr Opin Lipidol. 2002 Oct;13(5):461-70. Review.

Marcoux C, Hopkins PN, Wang T, Leary ET, Nakajima K, Davignon J, Cohn JS. Remnant-like particle cholesterol and triglyceride levels of hypertriglyceridemic patients in the fed and fasted state. J Lipid Res. 2000 Sep;41(9):1428-36.

Hall WL, Sanders KA, Sanders TA, Chowienczyk PJ. A high-fat meal enriched with eicosapentaenoic acid reduces postprandial arterial stiffness measured by digital volume pulse analysis in healthy men. J Nutr. 2008 Feb;138(2):287-91.

Burdge GC, Powell J, Dadd T, Talbot D, Civil J, Calder PC. Acute consumption of fish oil improves postprandial VLDL profiles in healthy men aged 50-65 years. Br J Nutr. 2009 Jul;102(1):160-5. Epub 2009 Jan 13.

Zampelas A, Peel AS, Gould BJ, Wright J, Williams CM. Polyunsaturated fatty acids of the n-6 and n-3 series: effects on postprandial lipid and apolipoprotein levels in healthy men. Eur J Clin Nutr. 1994 Dec;48(12):842-8.

Armah CK, Jackson KG, Doman I, James L, Cheghani F, Minihane AM. Fish oil fatty acids improve postprandial vascular reactivity in healthy men. Clin Sci (Lond). 2008 Jun;114(11):679-86.

Rontoyanni VG, Hall WL, Pombo-Rodrigues S, Appleton A, Chung R, Sanders TA. A comparison of the changes in cardiac output and systemic vascular resistance during exercise following high-fat meals containing DHA or EPA. Br J Nutr. 2012 Feb 21:1-8. [Epub ahead of print]

Responsible Party:	Dr Wendy Hall, Lecturer in Nutritional Sciences, King's College London
ClinicalTrials.gov Identifier:	NCT01618071 History of Changes
Other Study ID Numbers:	DRINC 11-LO-0116, BB/1005862/1
Study First Received:	June 8, 2012
Last Updated:	October 10, 2012
Health Authority:	UK: National Research Ethics Service

Keywords provided by King's College London:

n-3 PUFA
Endothelial cells
Nitric oxide
Oxidative stress

Blood pressure
Vasodilation
Lipemia
Unsaturated dietary fats

Additional relevant MeSH terms:

Hyperlipidemias
Flushing
Hyperemia
Hot Flashes
Dyslipidemias

Lipid Metabolism Disorders
Metabolic Diseases
Signs and Symptoms
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on May 16, 2013