Intervention With Omega Fatty Acids in High-risk Patients

Study Overview
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Brief Summary
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In order to reduce cardiovascular risk, current European guidelines recommend a diet low on saturated fatty acid through replacement with polyunsaturated fatty acids (PUFA). Polyunsaturated fatty acids can be classified into omega-3 and omega-6. However the results from recent meta-analyses investigating coronary risk outcomes did not clearly support a low intake of saturated fatty acids and a high intake of omega-3 or omega-6. The aim of this study is to investigate the short term effects of a high intake of PUFAs on microvascular function, lipids, inflammation and other cardiovascular risk factors in inactive patients with increased waistline.

Official Title
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Intervention With Omega Fatty Acids in High-risk Patients With Hypertriglyceridemic Waist

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Dietary Supplement: Omega-3 Fatty Acid
* Dietary Supplement: Omega-6 Fatty Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Waist circumference ≥ 94 cm in men and ≥ 80 cm in women Physical inactivity (< 2 h vigorous/active exercise training per week) Exclusion Criteria: Regular use of certain prescription medications at baseline Severe psychiatric illness Pregnancy Pacemaker or implantable cardioverter defibrillator Cigarette smoking Previous coronary intervention Concomitant use of dietary supplements Use of omega-3 supplements at baseline Alcohol or drug abuse or any condition associated with poor compliance. Scheduled hospitalisation during the course of the study. Participation in a clinical trial in the last 12 weeks, or prior randomisation. Blood donation within the preceding 12 weeks. Diabetes Mellitus Type 1 or type 2 Triglycerides > 5 mmol/l Previous bariatric surgery Malabsorption disorder

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omega-3 fatty acid<br>Omega-3 fatty acids for 8 weeks, dosage are 3 and 4 g/day for women and men, respectively. | Dietary Supplement: Omega-3 Fatty Acid<br>* Experimental: Omega-3 fatty acid In the intervention period the participants will receive a daily supplement of omega-3 fatty acids for 8 weeks, where the dosage are 3 and 4 g/day for women and men, respectively. The omega-3 supplement is a hydrolyzed and reesterified TAG fish oil, containing 33 area percent eicosapentaenoic acid and 22 area percent docosahexaenoic acid.<br>* Other names: N-3 PUFA;|
| Experimental: Omega-6 fatty acid<br>Omega-6 fatty acids for 8 weeks, dosage are 20 and 27 g/day for women and men, respectively. | Dietary Supplement: Omega-6 Fatty Acid<br>* Experimental: Omega-6 fatty acid In the intervention period the participants will receive a daily supplement of omega-6 fatty acid for 8 weeks, where the dosage are 20 and 27 g/day for women and men, respectively. The omega-6 supplement is a high-quality organic, cold pressed and filtered safflower oil, containing 68-83% linoleic acid, 5-15% saturated fatty acid, 8-21% oleic acid, 0,0-0,5% ALA and maximum 2% other fatty acids.<br>* Other names: N-6 PUFA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in lipid profile | High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol and triglycerides (TG) will be measured in plasma/serum (mmol/L). | Measured at baseline and after 8 weeks | 
| Changes in particle concentrations of lipoproteins of different sizes | Particle concentration (nmol/L) of lipoprotein of different sizes will be calculated from the measured amplitude of their spectroscopically lipid methyl group NMR signals. | Measured at baseline and week 8 | 
| Changes in lipoprotein particle sizes | Lipoprotein particle size (nm) analysis will be performed by proton nuclear magnetic resonance (NMR) spectroscopy. The size will be derived from the sum of diameter of each subclass multiplied by its relative mass percentage based on its methyl NMR signal. | Measured at baseline and week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in body composition | Body composition will be measured by bioelectrical impedance (InBody 720). | Measured at baseline and week 8 | 
| Changes in body weight |  | Measured at baseline and week 8 | 
| Changes in waist and hip circumference |  | Measured at baseline and week 8 | 
| Changes in circulating markers of inflammation, also including adipokines and kynurenine | Inflammatory markers and adipokines will be measured in serum/plasma, e.g tumor necrosis factor-α (TNF-α), interleukins, macrophage inflammatory protein 1-α (MIP-1-α) and granulocyte-macrophage colony stimulating factor (GM-CSF). | Measured at baseline and week 8 | 
| Changes in markers of inflammation in adipose tissue | Inflammatory markers like TNF-α, interleukins, GM-CSF and adiponectin in will be measured in adipose tissue (pg/mg tissue). | Measured at baseline and week 8 | 
| Changes in one carbon metabolites | Choline, betaine and related metabolites and B-vitamins involved in 1-carbon metabolism. | Measured at baseline and week 8 | 
| Changes in microbiota | Bacterial DNA in stool samples will be subjected to high-throughput barcode multiplex sequencing of the 16s ribosomal RNA gene (rRNA). | Measured at baseline and week 8 | 
| Changes in endothelial function | Vascular reactivity index (VRI) will be measured by monitoring fingertip temperature changes during a reactive hyperemia protocol. | Measured at baseline and week 8 | 
| Changes in carnitine and metabolites | Trimethylamine N-oxide (TMAO), carnitine, acylcarnitines and fatty acids will be measured in serum/plasma. | Measured at baseline and week 8 | 
| Changes in gene expression in adipose tissue | Gene expression in adipose tissue will be measured by microarray and quantitative PCR. | Measured at baseline and week 8 | 
| Changes in amino acids | Amino acids, methylated amino acids and metabolites will be measured in serum/plasma. | Measured at baseline and week 8 | 
| Changes in gene expression i whole blood | Gene expression in full blood will be measured by quantitative PCR. | Measured at baseline and week 8 | 
| Changes in apolipoproteins | Apolipoproteins A1, A2, B, C2, C3 and E will be measured in serum by a multiplex kit. | Measured at baseline and week 8 |