This study will evaluate the effects of dietary composition on energy expenditure and chronic disease risk factors, while also exploring physiological mechanisms underlying these effects.
Many overweight and obese people can lose weight for a few months, but most have difficulty maintaining weight loss over the long term. One explanation for the poor long-term outcome of weight-loss diets relates to behavior, in that motivation to adhere to restrictive regimens typically diminishes with time. An alternative explanation is that weight loss elicits biological adaptations - specifically a decline in energy expenditure and an increase in hunger - that promote weight regain. The purpose of this study is to evaluate the effects of dietary composition on energy expenditure and risk for chronic diseases, while also exploring physiological mechanisms underlying these effects. The study will be performed in collaboration with Framingham State University, providing a novel and feasible method for feeding subjects in dining halls and monitoring compliance. Following 12±2% weight loss on a standard run-in diet, 150 adults (aged 18 to 65 years) will be randomly assigned to one of three weight-loss maintenance diets controlled for protein content (20% of energy) and varying widely in dietary carbohydrate-to-fat ratio: Low-carbohydrate (20% of energy from carbohydrate, 60% fat), Moderate- carbohydrate (40% carbohydrate, 40% fat), High-carbohydrate (60% carbohydrate, 20% fat). During the weight-loss maintenance phase, energy intake will be adjusted to prevent changes in body weight. The primary outcome will be change in total energy expenditure (indirect calorimetry using stable isotopes) through 20 weeks. Secondary outcomes during weight maintenance will include resting energy expenditure (indirect calorimetry using respiratory gas exchange), physical activity (accelerometry), measures of insulin resistance and skeletal muscle work efficiency, components of the metabolic syndrome, and hormonal and metabolic measures that might inform an understanding of physiological mechanisms. We also will assess weight change during a 2-week ad libitum feeding phase, as an objective measure of dietary effects on hunger. The analytic framework for addressing study hypothesis will be repeated-measures analysis of variance, with adjustment for covariates (sex, race, ethnicity, age, anthropometrics, insulin sensitivity and secretion, obesity-related genes). We also will test each covariate for effect modification (covariate × diet interaction).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
234
Food provision throughout the study to all 3 dietary arms, with the following phases: 1) Weight loss; 2) Weight maintenance; 3) Ad libitum
Framingham State University
Framingham, Massachusetts, United States
Total Energy Expenditure, Assessed by Indirect Calorimetry Using Stable Isotopes
Total energy expenditure (TEE), assessed by indirect calorimetry using stable isotopes Total calories burned: Participants each drank about a cup of water containing special tracers which are measurable when they pass out of the body through urine. They provided a urine sample before they drank the water and then about every other day for the next two (2) weeks. Change: average (midpoint of test phase, end of test phase) - start of trial
Time frame: Start of Trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Resting Energy Expenditure, Assessed by Indirect Calorimetry Using Respiratory Gas Exchange
Resting energy expenditure, assessed by indirect calorimetry using respiratory gas exchange Calories burned while resting: Participants lied down with head and neck under a clear plastic "bubble," breathing room air. Gases in expired air were collected. Change: average (midpoint of test phase, end of test phase) - start of trial
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Physical Activity, Assessed by Accelerometry
Actigraph Accelerometer Change: average (midpoint of test phase, end of test phase) - start of trial An Actigraph Accelerometer measures movement, similar to a pedometer. Data are reported as counts (divided by 1,000) per day. Each participant wore the the accelerometer on the right hip for 7 days at each time point.
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Skeletal Muscle Work Efficiency
Efficiency is expressed as percentage ratio of power generated during cycle ergometry (with conversion of Watts to kcal/min using a factor of 0.01433) to energy expenditure above resting. Change: end of test phase - start of trial.
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
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Leptin (Start of Trial)
Leptin levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)). Changes (see Outcome 6) are expressed in percentage units (100%×(exp(change in log)-1)): average (midpoint of test phase, end of test phase) - start of trial
Time frame: Start of trial (time of randomization, post-weight loss)
Leptin (% Change)
Leptin levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): average (midpoint of test phase, end of test phase) - start of trial
Time frame: Change through 20 weeks' weight loss maintenance
Ghrelin (Start of Trial)
Ghrelin levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)). Changes (see Outcome 8) are expressed in percentage units (100%×(exp(change in log)-1)): average (midpoint of test phase, end of test phase) - start of trial
Time frame: Start of trial (time of randomization, post-weight loss)
Ghrelin (% Change)
Ghrelin levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): average (midpoint of test phase, end of test phase) - start of trial
Time frame: Change through 20 weeks' weight loss maintenance
1,5-Anhydroglucitol
Biomeasure of carbohydrate intake Change, 10 weeks: midpoint of test phase - start of trial Change, 20 weeks: end of test phase - start of trial
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Glycemic Control, Assessed by HgA1c
Change, 10 weeks: midpoint of test phase - start of trial. Change, 20 weeks: end of test phase - start of trial.
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Triglycerides
Triglyceride levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units Change, 10 weeks: midpoint of test phase - start of trial Change, 20 weeks: end of test phase - start of trial
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Body Composition (DXA)
Body fat, presented as a % of total mass Participants each had a special scan (x-ray) to measure their amount of body fat. The special x-ray is called "dual-energy x-ray absorptiometry" (DXA). They were asked to lie still on a table for x-ray pictures. Change: end of test phase - start of trial
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Glucose
Glucose level, fasting blood draw Change: end of test phase - start of trial
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Change in Lipoprotein Particle Subfraction Distribution
Lipoprotein insulin resistance (LPIR) score was calculated from triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P). LPIR score is quantified on a scale of 0-100. Higher scores indicate worse outcome. Change: end of test phase - start of trial
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Total Cholesterol
Change: end of test phase - start of trial
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
HDL-Cholesterol
High-density lipoprotein cholesterol Change, 10 weeks: midpoint of test phase - start of trial. Change, 20 weeks: end of test phase - start of trial.
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Non-HDL-Cholesterol
Calculated by subtracting HDL-cholesterol from total cholesterol. Change: end of test phase - start of trial
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
LDL-Cholesterol
Low-density-lipoprotein cholesterol Change: end of test phase - start of trial
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Adiponectin (Start of Trial)
Total and high molecular weight adiponectin Adiponectin levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)). Changes (see Outcome 20) are expressed in percentage units (100%×(exp(change in log)-1)): end of test phase - start of trial
Time frame: Start of trial (time of randomization, post-weight loss)
Adiponectin (% Change)
Adiponeptin levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): end of test phase - start of trial
Time frame: Change through 20 weeks' weight loss maintenance
C-reactive Protein (Start of Trial)
C-reactive protein, marker of inflammation C-reactive protein levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)). Changes (see Outcome 22) are expressed in percentage units (100%×(exp(change in log)-1)): end of test phase - start of trial
Time frame: Start of trial (time of randomization, post-weight loss)
C-reactive Protein (% Change)
C-reactive protein, marker of inflammation C-reactive protein levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): end of test phase - start of trial
Time frame: Change through 20 weeks' weight loss maintenance
IL-6 (Start of Trial)
Interleukin-6, marker of inflammation Interleukin-6 levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)). Changes (see Outcome 24) are expressed in percentage units (100%×(exp(change in log)-1)): end of test phase - start of trial
Time frame: Start of trial (time of randomization, post-weight loss)
IL-6 (% Change)
Interleukin-6, marker of inflammation Interleukin-6 levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): end of test phase - start of trial
Time frame: Change through 20 weeks' weight loss maintenance
Blood Pressure
Systolic and diastolic blood pressure Change: end of test phase - start of trial
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Plasminogen Activator Inhibitor-1 (Start of Trial)
Plasminogen activator inhibitor-1 levels were log transformed for analysis. For reporting, the adjusted means and 95% Confidence Intervals were retransformed to the original units (exp(mean log)±exp(mean log)×(exp(SE log)-1)). Changes (see Outcome 27) are expressed in percentage units (100%×(exp(change in log)-1)): end of test phase - start of trial
Time frame: Start of trial (time of randomization, post-weight loss)
Plasminogen Activator Inhibitor-1 (% Change)
Plasminogen activator inhibitor-1 levels were log transformed for analysis. Change (expressed in percentage units, 100%×(exp(change in log)-1)): end of test phase - start of trial
Time frame: Change through 20 weeks' weight loss maintenance
Fibrinogen
Change: end of test phase - start of trial
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Insulin Secretion Determined as Blood Insulin Concentration 30 Minutes After Oral Glucose (Start of Trial)
Insulin level 30 minutes after consuming 75 grams of glucose
Time frame: Start of trial (time of randomization, post-weight loss)
Thyroxine (T4)
thyroid function test
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Free T4
free thyroxine, thyroid function test
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Thyroid Stimulating Hormone
Produced by the pituitary gland in the brain. Tells the thyroid gland to make thyroid hormones.
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Reverse T3
thyroid function test, inactive form of triiodothyronine (T3) Lifespan Bio kit was used for analysis. The range of this kit is 250 to 5000 pg/mL, which varies from other commercially available kits (about 10-fold greater values).
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Urinary Cortisol Excretion
cortisol (stress hormone) excreted in the urine over a 24-hour period
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Urinary Catecholamine - Adrenaline
catecholamine excreted in the urine over 24 hours, also known as epinephrine
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Urinary Catecholamine - Dopamine
catecholamine excreted in the urine over 24 hours
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Urinary Catecholamine - Noradrenaline
catecholamine excreted in the urine over 24 hours, also known as norepinephrine
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Insulin Sensitivity (Hepatic), Assessed by Frequently-sampled Oral Glucose Tolerance Test
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Insulin Sensitivity (Systemic), Assessed by Frequently-sampled Oral Glucose Tolerance Test
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Non-esterified Fatty Acids
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Serum Ketones/Ketoacids
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Lactate
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Metabolic Fuel Concentration in Serum (Glucose, Nonesterified Fatty Acids, Ketones/Ketoacids, Lactate)
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Insulin-like Growth Factor 1 (IGF-1)
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
IGF Binding Proteins
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Testosterone
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Estradiol
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Luteinizing Hormone
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Follicle Stimulating Hormone
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Body Weight Change During ad Libitum Feeding
Time frame: Ad libitum feeding period (weeks 21 and 22 following randomization)
Gut Microbiome Profile
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Serum Metabolomics Profile
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Change in Cognitive Function Related to Memory
California Verbal Learning Test - Second Edition \[CVLT-II\] and Digit Span Test
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Change in Cognitive Function Related to Processing Speed and Executive Function
Trail Making Test Parts A and B \[TMT-A, TMT-B\]
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Change in Self-reported Sleep Quality
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Change in Self-reported Depression Measure
Beck Depression Inventory-II \[BDI-II\]
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Change in Self-reported Mood/Anxiety
Mood and Anxiety Symptom Questionnaire \[MASQ\]
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Change in Self-reported Food Addiction Score
Yale Food Addiction Scale \[YFAS\]
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Change in Self-reported Emotional Eating Score
Emotional Eating Scale \[EES\]
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance
Change in Self-reported Binge Eating Score
Binge Eating Scale \[BES\]
Time frame: Start of trial (time of randomization, post-weight loss) through 20 weeks' weight loss maintenance