Palmitoleic Isomer Study

The fatty acids trans-C16:1 and cis-C16:1 have been associated with healthy plasma glucose
levels. Elevated glucose levels have been associated with diabetes. This study is designed to
determine whether there is a dose-response relation between how much trans-C16:1 and
cis-C16:1 you consume and how much appears in plasma. This information will be used to design
a future study to determine whether trans-C16:1 and cis-C16:1 could be used to treat
diabetes. Trans-C16:1 occurs naturally in dairy fat such as milk and cheese, while cis-C16:1
occurs naturally in nuts, particularly, macadamia nuts, and a plant called sea buckthorn. The
study will consist of two 9-week phases, with a minimum of a 4 week off-study period between
the two phases. Fasting blood will be drawn at baseline (first day of week 1), 3 weeks, 6
weeks and 9 weeks (4 total blood draws per phase or 8 total blood draws for 2 phases). During
each phase you will be asked to consume increasing numbers of vegetable oil capsules, 2 per
day during the first 3 weeks, 4 per day during the second 3 weeks, and 8 per day during the
third 3 weeks. During each of these periods you should take half the capsules in the morning
and half in the evening, with your meals. You will be randomly assigned to receive the
trans-C16:1 or cis-C16:1 during the first phase and the other during the second phase. The
total length of the study is about 18 weeks, not including the break between phase 1 and
phase 2 (not less than 4 weeks). The trans-C16:1 in the capsules will be in the form of
partially-hydrogenated soybean oil. The cis-C16:1 in the other capsules will be in the form
of sea buckthorn oil.

1. Inclusion criteria:

- Age ≥ 18 to ≤ 70 years

- BMI ≥ 25 kg/m2 ≤ 40 kg/m2

- Normotensive with or without medication

- Normal fasting plasma glucose levels (≤120 mg/dL)

- Normal kidney function as assessed by serum creatinine and blood urea nitrogen

- Normal liver function as assessed by serum glutamic pyruvic transaminase (SGPT),
serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase (ALP)

- Normal thyroid function defined as screening TSH within normal ranges, without or
with medication for at least 6 months

- Normal gastrointestinal function

2. Exclusion criteria:

- Use of supplements containing fish oil or other lipid supplements (e.g.,
flaxseed, primrose oil, sea buckthorn oil) within 3 months of study participation

- Greater than 2 servings/day combined of cheese, whole-fat milk or whole-fat
yogurt

- Diagnosed diabetes mellitus Type I or Type II and/or taking glucose lowering
medications (e.g., metformin, actos, januvia)

- Use of medication known to affect lipid metabolism (HMG-CoA reductase inhibitors
(statins, red yeast rice), bile acid sequestrants, cholesterol absorption
inhibitors (exetimibe [Zetia]), nicotinic acid agents, fibrates, probucol,
anticoagulants, hormone therapy medications containing estrogen, anabolic
steroids)

- Established major chronic diseases such as major cardiovascular disease (history
of myocardial infarction, stroke, symptomatic heart failure, coronary artery
bypass graft, or symptomatic peripheral arterial disease), active cancer, end
stage renal disease, dementia, severe chronic obstructive pulmonary disease,
significant liver disease

- Pregnancy or breastfeeding

- Unwillingness to adhere to study protocol

- No Social Security number (for payment and IRS forms).