Dietary Intervention for Visceral Adiposity

OBJECTIVES:

Specific Aim 1: To test, in a small clinical trial of 30 pre-menopausal African American
women, whether increased intake of dietary fiber embedded in a 12 week weight loss
intervention will reduce VAT accumulation more than a standard weight loss intervention.

Hypothesis 1: Women in the high dietary fiber intervention group will lose significantly more
VAT than women in the standard fiber group.

Specific Aim 2: To test, in a small clinical trial of 30 pre-menopausal African American
women, whether increased intake of dietary fiber embedded in a 12 week weight loss
intervention will improve cardiovascular risk factors more than a standard weight loss
intervention.

Hypothesis 2: Women in the high dietary fiber intervention group will have lower blood
pressure, fasting glucose, fasting lipids and inflammatory factors at 3-months compared to
women in the control group.

Specific Aim 3: To characterize our ability to recruit and retain 30 African-American,
premenopausal women to a 12 week weight loss intervention study

Specific Aim 4: To determine participant compliance with serum and other measurement
evaluations and dietary compliance logs.

METHODS AND MEASURES

Design:

This study will be a randomized masked controlled trial design of 30 pre-menopausal African
American women aged 20-50 years with BMI ≥ 30 kg/ m2 and waist circumference > 88 cm
evaluating the effect of fiber supplementation on change in abdominal fat deposition. The
fiber intervention will be nested within a 3-month weight loss trial. The placebo and active
interventions will appear identical to the participant. The only person who will know of the
intervention (fiber vs. placebo) is the Clinical Research Unit (CRU) (former General Clinical
Research Center) Nutrition staff. All women will have ~ 800 kcal/day calorie restriction, for
12 weeks, designed lead to 0.5 kg - 0.9 kg per wk weight loss or 9-18 kg lost during the
study. Diets will all contain at least 0.8 grams of protein/kg IBW and be limited to 15 grams
total fiber. Calorie restriction will occur either through CRU prepared meal replacements or
participant instituted calorie restriction learned via nutritional education sessions.
Participants will be randomized and started on the 12-week study intervention on a rolling
basis. At any one time, there will be 8 women enrolled in the study. The enrollment will
continue until all 30 women are started. The women will not be held and then started as a
group.

Randomization:

Although enrollment will be rolling, participants will be randomized in groups of eight to
ensure that the capacity of the metabolic kitchen is always maintained. The randomization
will be to one of four groups (1- intervention/feeding; 2- intervention/nutritional
education; 3- placebo/feeding; 4-placebo/nutritional education). Participants will be
randomized to one of these four groups at the close of her baseline visit. Randomization will
occur via envelope. There will be an envelope for fiber intervention and one for caloric
restriction method. The intervention envelope will contain four fiber cards (marked B) and
four placebo cards (marked A). The calorie restriction envelope will contain for meal
replacement cards (marked D) and four nutrition education cards (marked C). Participants will
be given randomization assignment by CRU staff. The PI and participants will be blinded to
the fiber intervention.

Setting:

This study will take place in two main settings, the CRU and each participant's home. All
clinical measurements, nutritional education, meal replacement pick- up and distribution
dietary supplements will take place at the CRU. The CRU has agreed to: 1) perform CT, RMR,
and anthropomorphic measures as indicated for screening, baseline and 12-week follow-up; 2)
draw, process and assay blood, as indicated, for screening, baseline and 12-week follow-up;
2) to provide two nutritional education sessions, two weeks apart (for the nutrition
education group); 3) to prepare and distribute lunch and dinner (for the meal replacement
group); 4) prepare and distribute daily fiber supplements for all participants; and 5) to
prepare, distribute and collect weekly food compliance logs from each participant.

Interventions:

Dietary Fiber Intervention:

Benefiber® powder will be used as our dietary supplement intervention. Benefiber® powder
contains wheat dextrin, a 100% natural fiber. It's taste-free, sugar-free, dissolves
completely in noncarbonated beverages and soft foods, and won't thicken. Benefiber® powder
can be mixed into any hot or cold beverage such as water, coffee, or juice; into soft foods
such as applesauce, pudding or yogurt; or cooked into recipes for such foods as muffins,
sauces or soups, without affecting the taste or consistency. Benefiber® powder is not
recommended for carbonated beverages. Benefiber has a shelf life of 2 years when stored at a
controlled room temperature of 20-25°C (68-77°F). Benefiber® Powder, which contains less than
20 ppm of gluten and is therefore considered "gluten-free," based on both the FDA and the
Codex Alimentarius Commission's proposed definition of less than 20 ppm. Participants in the
intervention arm will receive 3 supplement packets to be consumed per day.

Each active dietary supplement packet contains 8 grams of Benefiber® powder and 3 grams of
TRUE® lemon flavoring, a 100% natural with no artificial ingredients or sweeteners,
preservatives, sodium or gluten. The TRUE® Lemon product is made from cold-pressed and
crystallized lemons which contain 0 calories and 0g carbohydrates. Each placebo dietary
supplement packet contains 8 grams of Splenda and 3 grams of true lemon sweetener. Each
packet is designed to be added to 8 oz of fluid. The three packets should be consumed each
day in a total of 24 fluid ounces.

Weight Loss Methods:

All participants will have a daily caloric restriction of ~ 800 kcal in order to facilitate a
loss of 0.5 kg - 0.9 kg per week weight loss or a 9-18 kg loss during the 12-week study
period. All participants will undergo a resting metabolic rate determination using
MedGraphics Ultima™ metabolic cart and the accompanying Breeze software. Based on the caloric
need determined to maintain weight, a new caloric plan, 800 kcal lower than basal needs, will
be determined. At minimum, however, all women will receive 1000 kcal per day. Once caloric
goals are determined, these will be achieved with through CRU-prepared meal replacements or
participant- instituted calorie restriction techniques learned via nutritional education
group sessions.

Participants receiving nutritional education will two individual sessions (spaced approx. 2
weeks apart). The nutritional sessions will focus on knowledge, self-regulation, motivation,
experience and environment.

All participants will be weighed at baseline and then weekly until the close of the study,
week 13. Additionally, all participants will, with CRU-prepared meals, be asked to return
uneaten food, record any foods eaten that were not part of the plan and complete weekly food
compliance logs. Participants with self-directed food selection after nutritional education
will be asked to completed detailed records of foods selected each day. All logs and food
records will be reviewed by the PI and the CRU study dietician. If participants have: 1)
increased weight by ≥ 5 pounds between weigh-in sessions; 2) a trend of weight gain for two
consecutive sessions; or 3) failed to return 2 consecutive food logs; they will be flagged
for additional nutritional counseling.

OUTCOMES Study Outcomes: The primary outcome, change in VAT between baseline and 12 weeks,
will be obtained via repeat computed tomography (CT) scans. The secondary outcomes are change
in CVD risk factors (blood pressure, fasting lipids, insulin sensitivity, C-reactive protein)
and liver attenuation. Abdominal fat mass will be measured at the L4/L5 vertebral regions by
CT. Height and weight will be measured to the nearest 0.5 cm and 0.1 kg, respectively, and
BMI will be calculated (kg/m2). Systolic and diastolic blood pressure will be obtained after
a 5-minute rest; the average of the final two of three measurements will be used in analysis.
Fasting blood samples will be collected for the measurement of glucose, insulin, LDL,
HDL,25-OH vitamin D, ghrelin, adiponectin, TNF-alpha, IL-6 and high sensitivity C-reactive
protein. Insulin resistance will be calculated via a HOMA model. Covariates such as smoking
status, physical activity, alcohol intake, sleep, and depressive symptoms will be ascertained
at baseline.

Inclusion Criteria:

- Pre-menopausal

- Self-identified as an African-American woman

- Aged 20-50 years

- Willing and able to provide informed consent

- No contraindication to weight loss

Exclusion Criteria:

- Diabetes or currently taking medication to lower blood sugar

- Currently on lipid lowering medications

- Currently taking chronic steroids

- Current diagnosis of kidney or heart failure

- Untreated hypothyroidism or hyperthyroidism

- BMI < 30 kg/m2 or waist circumference < 88 cm

- Current fiber supplementation

- Current pregnancy

- Body mass > 140 kg (CT limit)

- Inability to speak or read English

- Gastrointestinal disorders that prohibit the increased consumption of fiber

- Current participation in a structured weight loss/diet intervention program

- Inability to consume artificial sweeteners

- Inability or unwillingness to travel to the CRU during operating hours at the required
frequency.