Differential Thrombogenesis by EPA and DHA Mediated by HDL

The goal of this study is to learn more about omega-3 polyunsaturated fatty acids supplementation on blood lipid profile and platelets in patients with high cholesterol levels.

The purpose of this research is to gather information on the safety and effect of two different fish oils, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

Participants will:

Visit the clinic 5 times during study checkups, tests and blood collection. Randomized to either the EPA or the DHA supplementation group. Be given a 28-day food and activity log.

Epidemiological studies suggest that consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) derived from fish oil, mainly consisting of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is associated with lower cardiovascular risk. However, interventional clinical trials aimed at reducing cardiovascular incidents by n-3 PUFAs supplementations have yielded inconsistent results. An intriguing fact is that only the outcome trials using EPA, but not those testing EPA/DHA mixed regimens, showed beneficial results. This discrepancy begs the question of whether EPA and DHA have differential effects and whether DHA blunts the cardiovascular benefits of EPA. However, no head-to-head clinical trial comparison of the biological effects of EPA and DHA in the hyperlipidemia patients has been reported. Hence, a well-designed, controlled, proof-of-concept clinical study testing EPA versus DHA in a relevant population is urgently required. In this study, the human subjects with atherogenic dyslipidemia will be randomized to dietary supplementation with four grams of either EPA or DHA n-3 PUFAs for eight weeks. At baseline and after the supplementation, various markers of thrombogenesis will be assessed, including biomarkers of the clotting cascade, thromboelastography, urinary thromboxane metabolites, whole blood aggregation, platelet aggregation, and flow cytometry analysis of platelets and platelet-leukocyte aggregates will also be performed.

Eligibility Criteria:
Inclusion Criteria:

* Fasting TG levels ≥ 150 mg/dL and \< 500 mg/dL and HDL-C ≤ 40 (men) or ≤ 50 (women)
* LDL-C \> 40 mg/dL and ≤ 130 mg/dL
* Able to provide informed consent and adhere to study schedules
* Agree to follow and maintain a relatively stable and low fatty fish intake diet (\<3 servings per week)

Exclusion Criteria:

* Female with pregnancy, planned pregnancy (within the study period), or currently breastfeeding.
* Subjects with weight changes greater than 20% over the past 3 months
* Subjects planning a significant change in diet or exercise levels
* Malabsorption syndrome and/or chronic diarrhea
* Use of dietary supplements containing n-3 PUFA fatty acids
* Frequent consumption of n-3 PUFA-enriched fish (\>3 times a week)
* Abnormal liver, kidney, or thyroid functions
* Drug or alcohol abuse within 6 months or significant mental/psychological impairment
* Current smokers
* Subjects taking daily aspirin, NSAIDs, anticoagulant, or corticosteroids
* Subjects with known bleeding disorders (for example, hemophilia)
* Known sensitivity or allergy to fish, shellfish, or omega-3 fatty acid supplements
* Subjects requiring regular transfusions for any reason
* No ethnic/racial groups will be excluded