Effect of Fish Oil Enriched In Omega-11 Fatty Acid On Lipoprotein Metabolism In Adults

Serum cholesterol is transported by lipoproteins, such as VLDL, LDL and HDL, which vary in
their relationship to cardiovascular disease risk. LDL, for example, is proatherogenic,
whereas HDL is cardio-protective. Long-chain monounsaturated fatty acids (LCMUFA), fatty
acids over 18 carbons in length with a single double bond, have been shown in mice to
decrease proatherogenic lipoproteins, such as LDL, and reduce atherosclerosis. This study
will test the hypothesis that LCMUFA supplementation in humans will favorably alter the
lipoprotein lipid profile in regard to cardiovascular disease risk. In addition, we will
assess other parameters related to lipoprotein composition and function, as well as other
biomarkers related to coagulation and inflammation, which have previously been shown to be
affected by supplementation with omega-3 fatty acids.

This clinical research project is designed as a pilot, randomized, double-blinded, crossover
study that will investigate the effect of a fish oil enriched with LCMUFA on lipoprotein
metabolism. Subjects will receive control fish oil enriched in oleic acid, a monounsaturated
fatty acid (C18:1), or a fish oil supplement produced from Saury fish (rich in LCMUFA) for
approximately 8-10 weeks, with a wash out period of 8-10 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 fatty acid
levels will be monitored to assess compliance.

- INCLUSION CRITERIA:

- Male and female participants 18 years of age or above.

- Subject must be healthy, with no known history of cardiovascular disease.

- Pre-menopausal or women of childbearing potential must be non-lactating and using an
effective form of birth control during the course of the study.

- 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 EPA/DHA in any form.

- Known sensitivity or allergy to fish, shellfish or omega-3 fatty acids supplements

- Subjects with known bleeding disorders (for example, Hemophilia)

- Subjects previously diagnosed with atrial fibrillation

- Subjects with clinically diagnosed hepatic disease (including but not limited to auto
immune disease, hepatitis and cirrhosis)

- 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 (AST or ALT) levels above 3x upper limit of normal

- Subjects with a TSH greater than 1.5xULN or clinical evidence of hypo or
hyperthyroidism

- Subjects taking supplements or medications that affect lipoproteins for at least the
past 8 weeks, such as fish oil supplements, bile-acid sequestrants, plant sterol
supplements, fibrates, statins or Niacin.

- Subjects with hemoglobin <10g/dL

- Subject with platelet counts <60x103/microliter

- Subjects with uncontrolled hypertension (resting blood pressure > 160 mmHg systolic
and /or > 100 mm Hg diastolic)

- Subject with uncontrolled diabetes (HbA1c greater than or equal to 10)

- Subjects who consume excessive alcohol (binge drinking on 5 or more days in the past
month)

- Subject participating in other clinical studies and/or receiving other investigational
drug products prior to randomization

- Subject taking PCSK9 inhibitors within 8 weeks prior to enrollment

- Subjects being treated with tamoxifen, estrogens, or progestins that have not been
stable for >4 weeks.

- Subjects initiating new medications or patients on multiple medications may also be
excluded according to investigator discretion

- 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.