Effect of 6-week Strawberry Supplementation on Insulin Action (STR2)

This study is a single-center, randomized and single blinded, placebo-controlled, 6-week,
parallel design study with follow-up to evaluate strawberry-associated chronic improvements
in insulin action resulting in reduced whole body insulin resistance and improved glucose
tolerance. This study will take approximately 11~12 weeks.

Subjects will follow an extremely limited polyphenolic diet throughout the duration of their
participation in the study.

The limited diet will begin 7 days before the first study visit and end before the last study
visit. Following the polyphenol-free 7-day run in period, at Week 0, subjects will be
scheduled to return to the Center for sequence randomization, an Oral Glucose Tolerance Test
(OGTT) as well as a Flow Mediated Dilation (FMD) procedure to measure endothelial function.
Subjects will incorporate either one of tow Placebo Beverages (PBO1, n=15; PBO2, n=15) or
Strawberry Beverage (STR, n=15, an optimal strawberry test dose of 40 g/d) into their diet
daily for a period of 6 weeks. Subjects will consume randomly assigned beverage twice per day
with their breakfast and dinner meals.

All subjects will be asked to come to the Center once a week where they will receive a week's
supply of beverages. Additionally, fasting clinical and laboratory variables,
anthropometrics, and vital sign measurements will be assessed at each bi-weekly visit at Week
3 and Week 5.

Participants will undergo the same procedures at the end of Week 6: fasting blood sample
collection for analysis of insulin, glucose, oxidative and inflammatory markers, an OGTT to
assess glucose handling, as well as a FMD procedure to assess endothelial function in
response to 6 weeks of either the Placebo or Strawberry treatment.

Subjects will be required to visit the Center 4 weeks after the end of their intervention
period (Week 10), at which time they will undergo their last anthropometrics and vital sign
measurements, a 4 hour OGTT, and the FMD procedure.

Inclusion Criteria:

- Must meet ONE or MORE of the criteria (1)-(5) associated with insulin resistance along
with all other criteria listed (6)-(9):

1. Blood glucose concentration between140-199 mg/dL at 2hr from OGTT.

2. Elevated fasting glucose (110 mg/dL≤ Fasting blood glucose <126 mg/dL)

3. Elevated fasting insulin (>75th percentile cutoff of 13.13 μU/mL)

4. Insulin resistance defined by the homeostasis model assessment method of insulin
resistance (HOMA-IR) (glucose [in millimoles per liter] × insulin [in microunits
per milliliter]/22.5) values of at least 2.5.

5. Waist circumference ≥ 110 cm because many epidemiology studies have been shown
that waist circumferences may be related to insulin resistance.

6. Nonsmokers

7. Not taking any medications that would interfere with outcomes of the study, i.e.
lipid lowering medications, anti-inflammatory drugs, or dietary supplements

8. 18 years of age and older

9. No clinical evidence of cardiovascular, metabolic, respiratory, renal,
gastrointestinal or hepatic disease

Exclusion Criteria:

- Pregnant and/or lactating.

- Allergy or intolerance to strawberries and dairy products.

- Current regular consumption of strawberries is > 2 servings per day.

- Fasting blood glucose ≥ 126 mg/dL. Subjects identified with elevated fasting
blood glucose levels will be advised to contact their primary care physician for
appropriate follow-up care.

- Taking over the counter antioxidant supplements or other supplements that may
interfere with the study procedures or endpoints.

- Subjects with unusual dietary habits (e.g. pica).

- Actively losing weight or trying to lose weight (unstable body weight
fluctuations of > 5 kg in a 60 day period).

- Excessive exercisers or trained athletes.

- Subjects with documented atherosclerotic disease, inflammatory disease, diabetes
mellitus, or other systemic diseases.

- Addicted to drugs and/or alcohol.

- Medically documented psychiatric or neurological disturbances.

- Smoker (past smoker may be allowed if cessation is > 2 years).