Acute Berry Intake on Metabolic Control and Cognitive Function

The proposed study will be conducted in humans according to Good Clinical Practice (GCP)
guidelines. All subjects will review and sign an Informed Consent Form approved by the
Illinois Institute of Technology's Institutional Review Boards (IRB) prior to screening.

This multi-center clinical trial is a randomized, single-blind, 2-arm, placebo-controlled,
within subject cross-over trial, featuring a repeated postprandial sampling paradigm to
evaluate the effects of acute dietary red raspberry intake on cognitive function,
inflammation, insulin sensitivity / glucose handling and vascular function in
overweight/obese older adults after consuming a standardized challenge meal.

A planned sample size of 30 will be enrolled into the study. This study will require one
initial screening visit and 3 study visits. This study will take approximately 3-4 weeks per
subject to complete.

The initial screening visit will provide subject with their site-specific, IRB-approved
informed consent document prior to the start of any study related procedures. Subject
eligibility will be determined through anthropometric measurements, vital signs, fasting
blood glucose test (finger prick), and completion of a survey relate to general eating,
health, mood and exercise habits.

Eligible subjects will follow a limited polyphenolic diet throughout the duration of their
participation, although stricter guidelines will be imposed during the 3 days prior to a
study visit. Shopping lists and meal plans will be provided to subjects, along with
counseling by the investigator's study dietitians, to help subjects adhere to the limited
polyphenolic diet. The trial will initiate with a 3-day food diary to assess background
(pre-study) dietary intake followed by counseling to follow a diet relatively low in
(poly)phenolic rich-beverages/foods, which will be maintained for the duration of the
experiment. After an initial 7 day run-in period on the limited polyphenolic diet, subjects
will be randomized to 1 of 2 treatment sequences. Treatment codes will be maintained by the
principal investigator/study physician. All subjects will receive both treatments, once each
on 2 different occasions and separated by at least 1 week. Red raspberries or placebo will be
provided with a standardized meal providing 840 kcal. A low-polyphenol snack will be provided
to subjects after their final cognitive assessment.

Each visit will last ~ 9.5 hours and subjects will be required to remain at the Clinical Unit
for the duration of the visit. Blood samples will be collected at 0 (fasting) and at 0.5 h, 1
h, 2 h, 4 h, 5 h, 6 h and 7.5 h via a catheter placed on the non-dominant arm by a registered
nurse. Cognitive function will be measured at 0 (fasting), 2 h, and 6 h. FMD or NIRS will be
conducted at the CNRC or the HNRCA, respectively at 0 (fasting), and at 1 h and 5 h.

Inclusion Criteria:

- BMI between 27 and 35 kg/m2 and/or waist circumference (>35 inches for women, >40
inches for men)

- Aged 55-70 years old

- Able to provide informed consent and comply with study procedures

- Willing to maintain stable body weight and follow his/her habitual diet and physical
activity patterns throughout the trial.

- Judged by the Investigator to be in general good health on the basis of medical
history and screening laboratory tests.

Exclusion Criteria:

- Current smoker and/or marijuana user, past smokers may be allowed in the study if
stopped >2 years

- Have a history or presence of atherosclerotic cardiovascular disease, inflammatory
disease, diabetes mellitus, or other systemic diseases, psychological or psychiatric
disorders

- Have recent surgery or injury to head

- Mini-Mental Status Exam score < 24 or Beck Depression Inventory score > 20

- Taking any medications that would interfere with outcomes of the study (i.e.,
lipid-lowering medications, anti-inflammatory drugs, and supplements, not including
multivitamin/mineral or calcium/Vit D supplements),

- Unstable use of any medication/supplement

- Have a history of cancer in the prior 5 years, except for non-melanoma skin cancer

- Addicted to drugs and/or alcohol (>2 drinks/day)

- Have been exposed to any non-registered drug product within last 30 days.

- Working overnight (e.g. 3rd shift of overnight workers)

- Excessive exercisers or trained athletes

- Have allergies/intolerances to berries.

- Vegetarian/vegan or have extreme dietary habits.

- Excessive coffee/tea drinker

- Actively losing weight/ trying to lose weight (unstable body weight fluctuations of >
5 kg in 3 months)

- Donated blood within last 3 months

- Female who is pregnant, planning to be pregnant, breastfeeding

- Current regular consumption of berries which exceeds > 2 servings per day

- The individual has a condition the Investigator believes would interfere with his or
her ability to provide informed consent or comply with the study protocol, or which
might confound the interpretation of the study results or put the person at undue
risk.