Coronary Heart Disease, Obesity, Weight Loss
Conditions
Keywords
Diet, Coronary heart disease, Obesity, Weight loss, Weight maintenance
Brief summary
The proposed research will demonstrate that alternate day modified fasting (ADMF) is a suitable alternative to daily calorie restriction (CR) for weight loss, weight maintenance, and heart disease prevention. Since many overweight and obese individuals find it difficult to adhere to daily CR, this diet option may improve adherence with these dietary restriction protocols. This, in turn, will allow a greater percent of the overweight and obese population to lose weight, maintain weight loss, and prevent future occurrences of coronary heart disease.
Detailed description
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.
Interventions
Sponsors
Pennington Biomedical Research Center
National Heart, Lung, and Blood Institute (NHLBI)
University of Illinois at Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Body Weight | Baseline to month 12 | Change in body weight from baseline to month 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Systolic Blood Pressure | 12 month interval | Change in systolic blood pressure from baseline to month 12 |
| Change in Fasting Glucose | 12 month interval | Change in fasting glucose from baseline to month 12 |
| Change in Fasting Insulin | 12 month interval | Change in fasting insulin from baseline to month 12 |
| Change in HDL Cholesterol | 12 month interval | Change in HDL cholesterol from baseline to month 12 |
| Change in Plasma C-reactive Protein Concentrations | 12 month interval | Change in plasma C-reactive protein concentrations from baseline to month 12 |
| Change in Plasma Homocysteine Concentrations | 12 month interval | Change in plasma Homocysteine concentrations from baseline to month 12 |
| Change in Insulin Resistance Measured by HOMA-IR | 12 month interval | Change in insulin resistance measured by HOMA-IR from baseline to month 12 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alternate Day Fasting (ADF) Fast day diet: 25% energy intake, Feast day diet: Ad libitum energy intake (alternating days)
Alternate day fasting | 34 |
| Calorie Restriction (CR) 75% energy intake every day
Calorie restriction | 35 |
| Control Usual diet
Control diet | 31 |
| Total | 100 |
Baseline characteristics
| Characteristic | Alternate Day Fasting (ADF) | Calorie Restriction (CR) | Control | Total |
|---|---|---|---|---|
| Age, Continuous | 44 Years STANDARD_DEVIATION 10 | 43 Years STANDARD_DEVIATION 12 | 44 Years STANDARD_DEVIATION 11 | 44 Years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 34 Participants | 31 Participants | 97 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 21 Participants | 20 Participants | 63 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 13 Participants | 11 Participants | 35 Participants |
| Sex: Female, Male Female | 30 Participants | 29 Participants | 27 Participants | 86 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 4 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 35 | 0 / 31 |
| other Total, other adverse events | 0 / 34 | 0 / 35 | 0 / 31 |
| serious Total, serious adverse events | 0 / 34 | 0 / 35 | 0 / 31 |
Outcome results
Primary
Body Weight
Change in body weight from baseline to month 12
Time frame: Baseline to month 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alternate Day Fasting (ADF) | Body Weight | -4.6 Percent change at month 12 | Standard Error 0.9 |
| Calorie Restriction (CR) | Body Weight | -4.5 Percent change at month 12 | Standard Error 0.9 |
| Control | Body Weight | 0.3 Percent change at month 12 | Standard Error 0.6 |
Secondary
Change in Fasting Glucose
Change in fasting glucose from baseline to month 12
Time frame: 12 month interval
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alternate Day Fasting (ADF) | Change in Fasting Glucose | 4.0 Percent change from baseline to month 12 | Standard Error 2 |
| Calorie Restriction (CR) | Change in Fasting Glucose | -1.9 Percent change from baseline to month 12 | Standard Error 3.3 |
| Control | Change in Fasting Glucose | 10.7 Percent change from baseline to month 12 | Standard Error 3.4 |
Secondary
Change in Fasting Insulin
Change in fasting insulin from baseline to month 12
Time frame: 12 month interval
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alternate Day Fasting (ADF) | Change in Fasting Insulin | -35 Percent change from baseline to month 12 | Standard Error 11 |
| Calorie Restriction (CR) | Change in Fasting Insulin | -28 Percent change from baseline to month 12 | Standard Error 9 |
| Control | Change in Fasting Insulin | -2.5 Percent change from baseline to month 12 | Standard Error 13 |
Secondary
Change in HDL Cholesterol
Change in HDL cholesterol from baseline to month 12
Time frame: 12 month interval
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alternate Day Fasting (ADF) | Change in HDL Cholesterol | 4.6 Percent change from baseline to month 12 | Standard Error 3.1 |
| Calorie Restriction (CR) | Change in HDL Cholesterol | -0.5 Percent change from baseline to month 12 | Standard Error 3.1 |
| Control | Change in HDL Cholesterol | -3.4 Percent change from baseline to month 12 | Standard Error 3.9 |
Secondary
Change in Insulin Resistance Measured by HOMA-IR
Change in insulin resistance measured by HOMA-IR from baseline to month 12
Time frame: 12 month interval
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alternate Day Fasting (ADF) | Change in Insulin Resistance Measured by HOMA-IR | -36 Percent change from baseline to month 12 | Standard Error 13 |
| Calorie Restriction (CR) | Change in Insulin Resistance Measured by HOMA-IR | -34 Percent change from baseline to month 12 | Standard Error 12 |
| Control | Change in Insulin Resistance Measured by HOMA-IR | 12 Percent change from baseline to month 12 | Standard Error 16 |
Secondary
Change in Plasma C-reactive Protein Concentrations
Change in plasma C-reactive protein concentrations from baseline to month 12
Time frame: 12 month interval
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alternate Day Fasting (ADF) | Change in Plasma C-reactive Protein Concentrations | -13.9 Percent change from baseline to month 12 | Standard Error 11.7 |
| Calorie Restriction (CR) | Change in Plasma C-reactive Protein Concentrations | -6.2 Percent change from baseline to month 12 | Standard Error 8.1 |
| Control | Change in Plasma C-reactive Protein Concentrations | 5.4 Percent change from baseline to month 12 | Standard Error 16.8 |
Secondary
Change in Plasma Homocysteine Concentrations
Change in plasma Homocysteine concentrations from baseline to month 12
Time frame: 12 month interval
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alternate Day Fasting (ADF) | Change in Plasma Homocysteine Concentrations | 0.2 Percent change from baseline to month 12 | Standard Error 4.3 |
| Calorie Restriction (CR) | Change in Plasma Homocysteine Concentrations | -1.2 Percent change from baseline to month 12 | Standard Error 3.2 |
| Control | Change in Plasma Homocysteine Concentrations | -2.6 Percent change from baseline to month 12 | Standard Error 3.3 |
Secondary
Change in Systolic Blood Pressure
Change in systolic blood pressure from baseline to month 12
Time frame: 12 month interval
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alternate Day Fasting (ADF) | Change in Systolic Blood Pressure | -3.5 Percent change from baseline to month 12 | Standard Error 2.3 |
| Calorie Restriction (CR) | Change in Systolic Blood Pressure | -2.9 Percent change from baseline to month 12 | Standard Error 2 |
| Control | Change in Systolic Blood Pressure | -2.6 Percent change from baseline to month 12 | Standard Error 4 |