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.
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, triglycerides, 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. Update at study conclusion 17.6.2025. Covid-19 halted our study progression leading to a partial cohort (final n=38). Covid-19 restrictions also prevented us from measuring plasma lipid metabolism enzymes and lipid mediated resolvins. As a results we expanded the lipoprotein lipidomics analysis to consist all three lipoprotein fractions (VLDL, LDL, and HDL) using LC/MS. Finally a clinical cardiovascular risk score assessment was also performed (CERT2/Hertta-test).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
68
3,9 grams of E-EPA (Icosapent ethyl) is added to participants' normal diet.
Wihuri Research Institute
Helsinki, Finland
LDL Aggregation Susceptibility
LDL aggregation susceptibility was induced in vitro by sphingomyelinase and measured using dynamic light scattering. Time-size curves were generated, and the inflection point (EC50)-the midpoint of the most rapid aggregation-was determined by nonlinear regression with a modified Hill equation. A longer time to reach EC50 indicates lower aggregation susceptibility, and thus a lower risk of future cardiovascular events.
Time frame: 28 days
Total Blood Triglycerides
Percentage change in blood triglycerides after IPE-supplementation (day 28) compared to the baseline (day 0). Percentage change was calculated as follows: \[(day 28 - day 0) / day 0\] x 100.
Time frame: 28 days
EPA Incorporation Into LDL
Total concentration of eicosapentaenoic acid in LDL lipoprotein fraction at baseline (day 0), and after IPE-supplementation (day 28).
Time frame: 28 days
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