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.

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.

INCLUSION CRITERIA:

• Male and female participants 18 years of age or above.
• Subject must be healthy, with no known history of cardiovascular disease.
• Subject understands protocol and provides written, informed consent in addition to a willingness to comply with specified follow-up evaluations.

EXCLUSION CRITERIA:

• Pregnancy, planned pregnancy (within the study period) or women currently breastfeeding.
• Subjects with weight changes greater than 20% over the past 3 months.
• Subjects planning a significant change in diet or exercise levels.
• Subjects already consuming more than 1.5 g per day of Eicosapentaenoic Acid (EPA) or Docosahexaenoic Acid (DHA) in any form.
• Subjects taking supplements or medications that affect lipoproteins for at least the past six weeks including fish oil supplements, bile-acid sequestrants, plant sterol supplements, fibrates, statins or Niacin.
• Subjects diagnosed with cancer or IBD, or that have taken diarrhea inhibitors, laxatives or prebiotics in the week before stool sampling (optional), or antibiotics within 3 months before sampling.
• Subjects taking daily aspirin or other anti-platelet or anti-coagulants agents (Plavix).
• History of prostate Cancer
• Subjects with known bleeding disorders (for example, Hemophilia)
• Known sensitivity or allergy to fish, shellfish or omega-3 fatty acids supplements
• Subjects with chronic diarrhea, gastric bypass or lap-band procedures, ostomies, bowel motility problems, or other conditions that could affect intestinal fat absorption
• Subjects with any acute and life-threatening condition, such as prior sudden cardiac arrest, acute myocardial infarction (last three months), stroke, embolism
• Liver enzymes (aspartate aminotransferase (AST) or alanine transaminase (ALT)) levels above 3x upper limit of normal
• Subjects initiating new medications or patients on multiple medications may also be excluded according to investigator discretion
• Subjects previously diagnosed with cardiac dysrhythmia
• Subjects with clinically diagnosed hepatic disease (including but not limited to auto immune disease, hepatitis and cirrhosis)
• Anticipated surgery during the study period
• Blood donation in the last 2 weeks or planned blood donation during the study
• Subjects requiring regular transfusions for any reason
• Subjects may also be excluded for any reason that may compromise their safety or the accuracy of research data.
• Subjects being treated with tamoxifen, estrogens, or progestins that have not been stable for >4 weeks.
• Subjects that thyroid stimulating hormone (TSH) levels are greater than 1.5 x Upper Limit of Normal (ULN) or clinical evidence of hypothyroidism

20 weeks