Comparison of EPA and DHA-Rich Fish Oils on Lipoprotein Metabolism In Adults

Phase 2

Completed

Conditions: PCSK9
Lipoprotein Metabolism
Proteomics

Interventions: Drug: DHA-rich fish oil
Drug: EPA-rich fish oil

Registration Number: NCT02514070

Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Brief Summary: Background:

- Metabolism is what the body does to turn food into energy. Omega-3 fatty acids are substances found in foods such as cold-water fish and shellfish that are essential for good health. Researchers want to see the effect of two fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on metabolism. They may be beneficial to cardiovascular health.

Objective:

- To understand the effects of EPA and DHA on metabolism.

Eligibility:

- Healthy people ages 18 years or above with plasma triglyceride (a type of fat in the blood) levels of 100 mg/dL or higher

Design:

* The study will last 20 to 24 weeks.

* Participants will have 4 visits to the NIH Clinical Center. These will include:

* Medical history

* Physical Fasting blood and urine tests

* CAVI tests: blood pressure is taken in the arms and legs, and the heart is monitored.

* Participants will take an EPA/DHA dietary supplement. They will take 4 gel capsules, 3 times a day, for 6 or 7 weeks. Then they will not take the capsules for 8 to 10 weeks (a wash-out period). They will then take the capsules again for 6 or 7 weeks.

* Participants will keep a food journal.

Detailed Description: This is a novel randomized crossover, double-blinded pilot study that aims to investigate the effects of different omega-3 fatty acids, namely EPA and DHA, on lipoprotein metabolism. Subjects will be unblinded for performance of measurements after they complete the study. Subjects will receive EPA or DHA supplements for approximately 6 weeks with a wash out period of 8 weeks between the two arms of the study. The study consists of 4 outpatient visits when laboratory or research samples and CAVI tests will be performed. A 7-day food diary, pill count, and red cell membrane n-3 levels will be monitored to assess compliance.

Serum cholesterol is transported by lipoproteins, such as VLDL, LDL and HDL, which vary in their relationship to cardiovascular risk. LDL is proatherogenic, whereas HDL is cardio-protective. Fish oil supplementation, such as EPA and DHA, has been shown to reduce triglycerides. EPA supplementation has also been shown to lower LDL-C, whereas DHA can raise both LDL-C and HDL-C. These differential effects on lipoproteins may alter the cardiovascular protection afforded by fish oil supplementation. This study will test the hypothesis that EPA and DHA may differ in their LDL-C lowering ability because of differences in how they modulate plasma PCSK9 levels, which is a major determinant of LDL-C levels. In addition, we will assess other parameters related to lipoprotein composition and function that may impact the cardioprotective effect of EPA and DHA. Other reported beneficial effects of omega-3 fatty acid supplementation, such as decreased platelet coagulability, markers of inflammation and changes in guy microbiota, will also be monitored.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 44

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
DHA-rich fish oil arm then EPA-rich fish oil arm	DHA-rich fish oil	Subjects randomized to the DHA-rich fish oil arm will take the equivalent to 3g of DHA /day (12 gel capsules/day) for 6 more or less 1 weeks and cross-over to the EPA-rich capsule arm
EPA-rich fish oil arm then DHA-rich fish oil arm	EPA-rich fish oil	Subjects randomized to the EPA-rich fish oil arm will take the equivalent to 3g of EPA /day (12 gel capsules/day) for 6 more or less 1 weeks and cross-over to the DHA-rich capsule arm

Primary Outcome Measures

Name	Time	Method
Plasma PCSK9 Levels at Baseline and End of 6 Week Intervention	baseline to 6 weeks of intervention	Measure plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) level, at baseline, after 6 weeks of Eicosapentaenoic acid (EPA) or Docosahexaenoic acid (DHA) fish oil supplementation.

Secondary Outcome Measures

Name	Time	Method
Plasma Levels in Triglyceride, Cholesterol, and Lipoprotein From Baseline to 6 Weeks	Baseline to 6 weeks of intervention	Measure plasma levels at baseline to 6 weeks of intervention for the following: triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), lipoprotein particle composition and size, and high-density lipoprotein (HDL) cholesterol efflux capacity.