A Study of Different Types of Fatty Acid on Risk Factors for Heart Disease

Study Overview
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Brief Summary
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Experimental elevation of non-esterified fatty acids (NEFA) impairs endothelial function and insulin sensitivity but the impact of NEFA composition is unknown. The objective was to test the effect of acute elevation of NEFA enriched with either saturated fatty acids (SFA) or SFA with long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) on postprandial vascular function measured via flow-mediated dilatation (FMD), laser Doppler iontophoresis (LDI) and digital volume pulse (DVP), followed by a hyperinsulinaemic-euglycaemic clamp as a measure of whole body insulin sensitivity.

Detailed Description
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To investigate potential diet-gene interactions, potential subjects (n=370) were prospectively genotyped for the eNOS Glu298Asp polymorphism, of which 35 were Asp298 and 150 were Glu298 homozygotes. Three subjects in the Asp298 group were unable to participate, two were unsuitable according to selection criteria and one subject subsequently withdrew from the study. Subjects homozygous for Asp298 (n=29) and Glu298 (n=30) were therefore selected, balanced for gender, age and BMI.

Official Title
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Acute Elevation of Non-esterified Fatty Acids on Endothelial Function and Insulin Sensitivity: A Comparison of Saturated and Long Chain n-3 Polyunsaturated Fatty Acids During the Postprandial Phase

Conditions
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Cardiovascular Risk Factors

Intervention / Treatment
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* Dietary Supplement: Absence or presence of fish oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Either homozygous for eNOS Glu298 (wildtype)or eNOS Asp298 (variant) Exclusion Criteria: Smokers Raised fasting blood lipids Taking excessive fish oil supplements (>1g EPA/DHA per day) Taking medication known to influence blood lipids, blood pressure or blood clotting

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SFA<br>Oral dose of palmitic acid (SFA) given as a chocolate-flavoured drink every 30 min (0-390 min) with a continuous infusion of heparin (60-390 min). | Dietary Supplement: Absence or presence of fish oil<br>* Oral dose of saturated fat with or without fish oil and a heparin infusion<br>|
| Experimental: SFA + LC n-3 PUFA<br>Oral dose of palmitic acid and DHA-rich fish oil (SFA + LC n-3 PUFA) given as a chocolate-flavoured drink every 30 min (0-390 min) together with a continuous infusion of heparin (60-390 min). | Dietary Supplement: Absence or presence of fish oil<br>* Oral dose of saturated fat with or without fish oil and a heparin infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow-mediated dilatation |  | Change from baseline to 240 min | 
| Flow-mediated dilatation |  | Change from 240 min to 390 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Digital volume pulse |  | Change from baseline to 240 min | 
| Laser Doppler iontophoresis |  | Change from baseline to 240 min | 
| Insulin sensitivity |  | 390 min | 
| NEFA composition |  | Change from baseline to 240 min | 
| Circulating endothelial function markers |  | Change from baseline to 240 min | 
| Digital volume pulse |  | Change from 240 min to 390 min | 
| Laser Doppler iontophoresis |  | Change from 240 min to 390 min | 
| Circulating endothelial markers |  | Change from 240 min to 390 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endothelial function, Non-esterified fatty acids, Insulin sensitivity