Effects of a Standardized Freeze-dried Grape Powder on High Density Lipoprotein (HDL) Function in Metabolic Syndrome

This study will involve a 2-week "run-in" period and two 4-week "intervention" phases
separated by a 3 week "washout" non-intervention phase (for a total of 13 weeks). At the
start of each 4-week intervention period, subjects will be asked to participate in a
"postprandial challenge" test. Subjects will be asked to first follow a 2-week run-in control
period consuming habitual diets but refraining from consuming polyphenol-rich
foods/beverages, including tea, berries, grapes, juices, and wine. Subjects will then be
asked to consume 60 g of grape powder or placebo in random order, each for a 4-week
intervention period, separated by a 3-week washout period. Subjects will be asked to prepare
powder by mixing with water at breakfast (30 g) and dinner (30 g) and consume immediately
after mixing (or within 30 minutes). During each 4-week intervention period, subjects will be
asked to refrain from consuming polyphenol-rich foods/beverages. During the washout period
subjects will not be asked to consume the powder, but should abstain from consuming
polyphenol-rich foods/beverages. The grape powder is made from a composite of fresh red,
green and black California grapes, based on actual consumption patterns of consumers. It is a
mix of seeded and seedless varieties that have been frozen, ground with food-quality dry ice,
freeze-dried, and re-ground. Subjects will also be asked to maintain normal diet and exercise
habits throughout the study, with the exception being the consumption of polyphenol-rich
foods/beverages. Subjects will be asked to complete a 5-day dietary record (including 1
weekend day) and a 7-day physical activity diary at the baseline and end of each intervention
period. Subjects will come to the University of Connecticut Nutrition Department once every
other week (biweekly) to pick up the powder (in packets), which needs to be kept frozen until
consumption.

For the postprandial challenge tests, subjects will be asked to fast overnight (12 hours) and
then will be given a coconut oil-based lactose-free milkshake (1 g fat/kg body weight),
containing 60 g of either placebo or grape powder. Subjects will be asked to spend the test
day in the laboratory in a rested state and, with the exception of water, will not be
permitted to consume any additional food or beverages during the 6 hours after consuming the
milkshake. Subjects will be asked to abstain from alcohol and strenuous physical activity
24-hours prior to the postprandial test. To standardize short-term fat intake, subjects will
be given recipes and instructed to consume a low-fat evening meal (< 10 g fat) the night
prior to postprandial tests. Subjects will also be asked to complete a 1-day food record for
the day prior to the postprandial tests.

Inclusion Criteria:

- Age 30 to 70 years

- Having metabolic syndrome, meaning that subjects have at least 3 of the following
characteristics:

- Waist circumference ≥ 102 cm for men and ≥ 88 cm for women

- Triglycerides ≥ 150 mg/dL

- HDL cholesterol < 40 mg/dL for men and < 50 mg/dL for women

- Blood pressure ≥ 130/85 mm Hg or taking an anti-hypertensive medication

- Fasting blood glucose ≥ 100 mg/dL

Exclusion Criteria:

- Do not fulfill the classification of metabolic syndrome

- History of diabetes mellitus, cardiovascular disease, stroke, renal problems, liver
disease, endocrine disorder, inborn error of metabolism, eating disorder or cancer.

- Weight loss greater than 10% of body weight over preceding 4 weeks.

- Taking high-dose aspirin (≥150 mg/day) or anti-inflammatory prescriptions, or any
triglyceride- or glucose-lowering prescriptions or supplements, such as insulin,
sodium-glucose transport protein-2 (SGLT-2) inhibitors, glucagon-like peptide-1
(GLP-1) agonists, Fibrates (e.g., fenofibrates, gemfibrozil), Niacin (e.g., high dose
nicotinic acid, Niaspan) Sulphonylureas (e.g., Glucotrol, Amaryl), Thiazolidinediones
(e.g., Avandia, ACTOS, Rezulin), Meglitinides (e.g., Prandin, Starlix), Biguanides
(e.g., Metformin), Alpha-glucosidase inhibitors (e.g., Precose, Glyset), dipeptidyl
peptidase-4 (DPP-4) inhibitors (e.g., Januvia, Onglyza), prescription fish oil (e.g.,
Lovaza, Vascepa), high dose chromium, high dose fish oil, or cinnamon supplements etc.

- Triglycerides are higher than 500 mg/dL, glucose levels higher than 126 mg/dL, blood
pressure higher than 160/100 mmHg, and waist circumference higher than 200 cm.

- Allergy to coconut, milk, wheat, grapes or an allergy/intolerance to the placebo
ingredients.