The Effect of E-EPA on Circulating LDL and Plasma Lipid Metabolism

Study Overview
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Brief Summary
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40-70 healthy volunteers of ages 18 to 65 participate in a E-EPA-diet where 3,9 grams of E-EPA is added to their normal diet and lifestyles for a month. Blood samples will be collected before the study and at weeks 1 and 4 and also, two weeks after finishing the diet. Main study focuses are LDL aggregation susceptibility, lipid composition and proteoglycan binding affinity. In addition, important plasma lipid metabolism enzymes and lipid mediated resolvins are measured as well as several baseline characteristics.

Detailed Description
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Four grams of daily E-EPA was found to significantly decrease atherosclerotic cardiovascular diseases in the REDUCE-IT study. In the upcoming study the effect of E-EPA to low-density lipoprotein (LDL) aggregation susceptibility is measured using dynamic light scattering technique to continuously measure particles size while inducing aggregation. LDL Lipid composition is analyzed using electrospray mass spectrometer optimized for lipid measurements. Previously is reported that the aggregation susceptibility is affected by the lipid composition which is modifiable (Ruuth et. al. Eur.H.Journal 2018). Common disease factors such as total cholesterol, LDL, HDL, triglyserides, ApoB-100, ApoA-I, Lp(a) and different modified LDL levels are measured. Also, activities of lipid metabolism enzymes like PON-1, LCAT, CETP, PLTP and lipid mediated resolvins are looked into. Objective is to identify changes and possible pathways that are altered by the increase of E-EPA and to use the data to possibly explain the health benefits of EPA.

Official Title
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The Effect of Ethyl Eicosapentaenoic Acid on Circulating Low-density Lipoproteins and Plasma Lipid Metabolism in Healthy Volunteers

Conditions
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Atherosclerosis, Low-density Lipoproteins Aggregation Susceptibility, Low-density Lipoprotein Lipid Composition, Cardiovascular Diseases

Intervention / Treatment
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* Dietary Supplement: Ethyl-Eicosapentaenoic Acid (E-EPA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy normolipidemic Exclusion Criteria: Prescription of blood thinner medicine Circulating Low-density lipoprotein > 5mmol/l, Triglycerides >3mmol/l Chronic use of pain medication Fish allergy Pregnancy Breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Interventional Model Description: Baseline measurements are compared to different time points during the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E-EPA-diet group<br>All the study participants will receive the same treatment. 3.9g of E-EPA in capsules, which include 75µg of D3-vitamin, daily for 30 days. | Dietary Supplement: Ethyl-Eicosapentaenoic Acid (E-EPA)<br>* 3,9 grams of EPA is added to participants' normal diet.<br>* Other names: Icosapentaenoic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL Aggregation susceptibility | Lowering in LDL aggregation susceptibility | 30 days | 
| Lowering total triglycerides | Lowering of total circulating triglycerides | 30 days | 
| EPA incorporation into LDL | Incorporation of EPA into circulating LDL lipid composition | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increases in EPA mediated resolvins | Increases in circulating resolvins, derived from EPA | 30 days | 
| Changes in lipid metabolizing enzymes | Changes in activities of circulating lipid metabolizing enzymes such as PON-1, LCAT, PLTP and CETP | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atherosclerosis, E-EPA, LDL aggregation susceptibility, Lipidomics, Resolvins, PON-1, LCAT, PLTP, CETP, Proteglycan binding