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

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

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, 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.

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

Atherosclerosis, E-EPA, LDL aggregation susceptibility, Lipidomics, Resolvins, PON-1, LCAT, PLTP, CETP, Proteglycan binding

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.

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

Ruuth M, Nguyen SD, Vihervaara T, Hilvo M, Laajala TD, Kondadi PK, Gistera A, Lahteenmaki H, Kittila T, Huusko J, Uusitupa M, Schwab U, Savolainen MJ, Sinisalo J, Lokki ML, Nieminen MS, Jula A, Perola M, Yla-Herttula S, Rudel L, Oorni A, Baumann M, Baruch A, Laaksonen R, Ketelhuth DFJ, Aittokallio T, Jauhiainen M, Kakela R, Boren J, Williams KJ, Kovanen PT, Oorni K. Susceptibility of low-density lipoprotein particles to aggregate depends on particle lipidome, is modifiable, and associates with future cardiovascular deaths. Eur Heart J. 2018 Jul 14;39(27):2562-2573. doi: 10.1093/eurheartj/ehy319.

Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM; REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019 Jan 3;380(1):11-22. doi: 10.1056/NEJMoa1812792. Epub 2018 Nov 10.