Dietary Omega-7 Palmitoleic Acid-Rich Oil on Lipoprotein Metabolism and Satiety 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. Palmitoleic acid (cis-C16:1 n-7), an omega-7 fatty acid
with 16 carbons in length with a single double bound in the n-7 position, have been shown in
mice and human to decrease proatherogenic lipoproteins, such as LDL, and reduce
cardiovascular risk factors. This study will test the hypothesis that palmitoleate
supplementation in humans will favorably alter the lipoprotein lipid profile in regard to
cardiovascular disease risk. We will also 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 possibly affected by supplementation
with omega-7 fatty acid. In addition, previous animal studies have indicated the palmitoleate
induced satiety and suppressed bodyweight gain, possibly through enhancement of the release
of satiety hormones. In this clinical trial, we, therefore will also examine the effect of
concentrated palmitoleate on satiety.

This clinical research project is designed as a pilot, randomized, double-blinded, crossover
study that will investigate the effect of concentrated oil enriched with palmitoleate on
lipoprotein metabolism and satiety. Subjects will either receive control olive oil enriched
in oleic acid, a longer-chain monounsaturated fatty acid (cis-C18:1 n-9), or a concentrate
oil supplement produced from pollock fish (rich in palmitoleate) 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. The effect of the supplement on satiety will be assessed at
each visit.

- INCLUSION CRITERIA:

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

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

- Post-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 allergy or known hypersensitivity to fish, omega-3-acid ethyl esters,
omega-7 ethyl esters, other related drugs, or any component of study drugs

- Subjects with weight changes greater than 20% over the past 3 months.

- Subjects planning a significant change in diet or exercise levels.

- Subjects with BMI equal or below 25 kg/m(2) and/or triglyceride levels equal or below
100 mg/dL at any point.

- Subjects already consuming more than 2 g per day of MUFA, PUFA or other forms of fatty
acid supplement if determined by the inverstigator as having a potential to interfere
in the data quality or patient safety.

- Subjects with chronic diarrhea, gastric bypass or lap-band procedures, ostomies, bowel
motility problems, or other known conditions that could affect intestinal fat
absorption.

- Subjects with any acute and life-threatening condition, such but not limited to as
prior sudden cardiac arrest, acute myocardial infarction (last three months), stroke,
embolism as per investigator accessment.

- 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, Niacin or PCSK9 inhibitors.

- 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

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

- 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.

- Abnormal baseline laboratory values that are considered not clinically significant by
the PI will not exclude the subject.