Effects of Niacin On Fatty Acid Trapping

This study includes three phases, which each have a separate purpose. At this time, we are
only recruiting for Phase 2. The purpose of this particular phase is to measure the effects
of niacin after drinking a glass of heavy cream as a source of fat. We hope that studying
the way the body responds will help us better understand how niacin works.

In this study, we are interested in niacin's ability to lower triglycerides, or fat in the
blood. We are studying two different forms of niacin and comparing them to each other. The
two forms differ in how long they take to release niacin into the bloodstream. The first
form is called Nialor, and is sometimes called immediate-release niacin because it is
absorbed into the bloodstream quickly. The second form is called Niaspan, and is sometimes
called extended-release niacin because it is a time-released spansule that takes longer to
get into the bloodstream. We are comparing the two forms because we think that the time that
it takes to absorb niacin may affect how it works. We also want to understand one of the
common effects of niacin: skin flushing. Most people who take niacin experience flushing,
which is a hot flash. In this study, we are studying whether the two forms of niacin cause
different degrees of flushing. Niaspan is approved by the US Food and Drug Administration
(FDA) to treat unfavorable cholesterol levels and prevent heart attacks in those who have
already suffered heart attacks. Nialor is available over the counter as a supplement and
contains Silymarin (milk thistle) and Policosanol (an extract from sugar cane) in addition
to niacin.

Inclusion Criteria:

- Meet protocol defined criteria for atherogenic dyslipidemia phenotype

- Men and non-pregnant, non-lactating women between the ages of 22 and 75

- Fasting triglycerides <500 mg/dL

- Ability to understand and agree to informed consent

- Willingness to comply with study-related procedures

Exclusion Criteria:

- Dysbetalipoproteinemia

- History of extreme triglyceridemia (TG >500 mg/dL) or pancreatitis from
triglyceridemia, regardless of whether it is currently controlled

- LDL >190 mg/dL

- History of chronic renal insufficiency (serum creatinine >2.0 mg/dL)

- History of non-skin malignancy within the previous 5 years

- Subject reported history of HIV

- Uncontrolled thyroid disease

- Hypoalbuminemia (serum albumin >2.5 mg/dL)

- Exposure to an investigational drug within 6 weeks prior to the screening visit

- Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory
condition

- Major surgery within the previous 6 weeks

- Subjects who have undergone any organ transplant

- History of drug abuse within the past 3 years, or regular alcohol use >14 drinks per
week

- Women who are breast-feeding

- Women who are pregnant by urine pregnancy test at each visit

- Serious or unstable medical or psychological conditions that, in the opinion of the
investigator, would compromise the subject's safety or successful participation in
the study

- Change in statin dose within 6 weeks of the first experimental visit

- Use of the following non-statin lipid-altering therapy within 6 weeks of the first
experimental visit: Niacin > 100 mg/day (Niacor, Slo-Niacin, Niaspan, Advicor, or
supplemental niacin), Fibrates [gemfibrozil (Lopid), fenofibrate (Antara, Lofibra,
Tricor, Triglide)], Enterically active drugs [colestipol (Colestid), cholestyramine
(Questran), colesevelam (Welchol), ezetimibe (Zetia, Vytorin)], Red yeast rice, Fish
oil (Omacor, numerous supplements)

- Use of medications indicated for the treatment of diabetes within 6 weeks of the
screening visit

- Known intolerance or contraindication to niacin (e.g., moderate to severe gout,
severe peptic ulcer disease)

- Medical condition that would prohibit fasting (e.g., diagnosis of insulinoma or
postabsorptive hypoglycemia)

- Significant disinclination to dairy products (e.g., lactose intolerance, inviolable
dietary restrictions)

- History of anaphylactic reaction

- For indocyanine green substudy: iodine allergy or shellfish allergy (n.b. a subject
with an allergy can participate in the overall experiment, but will forego the
indocyanine green tracer study)

- Donation of blood 8 weeks and/or treatment with medications for psychiatric disorders

- Hemoglobin <10 g/dL