Alternate Day Fasting for Weight Loss, Weight Maintenance and Cardio-protection

Overweight and obese individuals are at increased risk for coronary heart disease (CHD).
Losing weight by means of dietary restriction greatly reduces vascular disease risk. The
majority of studies examiningmost common dietary restriction protocol s implemented is daily
calorie restriction (CR). Another dietary restriction regimen employed, although far less
commonly, is alternate day modified fasting (ADMF). ADMF involves a "feed day" where food is
consumed ad-libitum, alternated with a "fast day", where food intake is partially reduced.
Previous reports show that adherence to ADMF exceeds that of CR after 8 weeks of treatment.
This increased adherence to ADMF results in greater weight loss, which produces more
pronounced improvements in CHD risk. What has yet to be determined is whether adherence to
ADMF remains near maximal for longer treatment durations (24 weeks), and if this improved
adherence results in greater reductions in body weight and CHD risk, versus CR. Once weight
loss is achieved, weight maintenance is extremely important as CHD risk can increase if
weight is regained. Whether ADMF is an effective strategy for weight maintenance remains
unknown. Accordingly, the aims of this proposal are: Aim 1: To establish that adherence to
ADMF is greater than that of CR during a 24-week intervention period and to determine if
increased adherence to ADMF results in greater weight loss; Aim 2: To establish that greater
reductions in body weight by ADMF over a 24-week period will result in greater improvements
in traditional CHD risk parameters (blood pressure, plasma lipid levels, cholesterol
synthesis rate, LDL particle size, and CRP) and emerging CHD risk parameters (fat
cell-derived hormones, body fat distribution, and fat cell size) in comparison to CR; and Aim
3: To establish that ADMF is an effective diet therapy to maintain weight loss and sustain
improvements in CHD risk indicators, and to compare changes in cognitive and behavioral
components of eating between ADMF and CR subjects. A 52-week randomized, controlled,
parallel-arm feeding trial will be implemented to test these objectives. The trial will be
divided into 3 consecutive intervention periods: (1) 4-week baseline; (2) 24-week weight loss
with food provided; and (3) 24-week weight maintenance with no food provided. Overweight and
obese subjects (n = 90) will be randomized to 1 of 3 groups: (1) ADMF, 75% energy restriction
on the "fast day" and ad libitum fed on the "feed day"; (2) CR, 25% restriction everyday; or
3) control, 100% energy intake everyday. During the weight maintenance phase, ADMF subjects
will consume 25% of their energy needs on the "fast day" and 175% of their needs on the "feed
day", while CR and control subjects will consume 100% of their needs everyday. Our findings
will show that ADMF can be implemented as an alternative to CR to help overweight and obese
individuals lose weight, maintain weight loss, and sustain reductions in CHD risk. This study
will also generate insights into the specific behavioral changes that occur with ADMF that
explain why ADMF is a successful diet strategy for weight maintenance.

Inclusion criteria. Adult subjects meeting the following criteria will be eligible to
participate:

- Age between 18 to 65 years old

- BMI between 25.0 and 39.9 kg/m2

- Previously sedentary (<60 minutes/week of light activity corresponding to 2.5 to 4.0
metabolic equivalents (METs) for the 3 months prior to the study)

Exclusion criteria. Subjects excluded from participating in the study include those who:

- Have a history cardiovascular disease (prior angina, myocardial infarction or stroke)

- Are diabetic (fasting blood glucose > 126 mg/dl)

- Have a history of psychiatric disorders and/or eating disorders

- Are taking anti-depressant or anti-anxiety medications

- Are taking drugs that affect study outcomes (weight loss, lipid-lowering, or blood
pressure drugs)

- Are not weight stable for 3 months prior to the beginning of study (weight gain or
loss > 4 kg)

- Are not able to keep a food diary or activity log for 7 consecutive days during
screening

- Are perimenopausal or have an irregular menstrual cycle (menses that does not appear
every 27-32 days)

- Are claustrophobic or have implanted electrical devices (cardiac pacemaker or a
neurostimulator)

- Are pregnant, or trying to become pregnant

- Are smokers