Reduced Carbohydrate Versus Fat in Obese Subjects

Phase 2

Completed

Conditions: Obesity

Interventions: Other: Reduced fat diet
Other: Reduced carbohydrate diet
Device: fMRI
Device: PET

Registration Number: NCT00846040

Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary: Popular weight loss strategies often involve reducing an individual's consumption of carbohydrates or fat. However, no controlled study has been carried out to evaluate the effects of reducing carbohydrate versus fat consumption while keeping the other nutrients at standard levels to maintain an individual's weight. Researchers are interested in investigating how different restrictions of carbohydrates or fats affect the many processes involved in weight loss, including brain activity and blood and brain chemical composition.

Detailed Description: Popular weight loss strategies often prescribe a targeted reduction of dietary carbohydrate or fat. But surprisingly, no controlled human feeding study has ever investigated the effects of a selective reduction of dietary carbohydrate versus fat while keeping the other dietary macronutrients at their baseline weight-maintenance values. The present study was designed to address this knowledge gap and improve our understanding of how selective reduction of dietary fat versus carbohydrate may differentially impact the many feedback control processes that act to resist weight loss.

Objectives:

- To determine the comparative effects of two controlled fat- or carbohydrate-restricted diets and an outpatient weight loss program on blood and brain chemical composition, weight loss (fat and lean body mass), and regional brain activity in lean and obese individuals.

Eligibility:

- Healthy individuals between 18 and 45 years of age who are either lean (body mass index between 18.5 kg/m(2) and 25 kg/m(2)) or obese (body mass index above 30.0 kg/m(2), weight less than 350 pounds) and are right-handed.

Design:

* Lean participants: Participants will be screened with a medical history, physical examination, blood and urine tests, and weight maintenance observations (food diaries and physical activity monitors). For the scanning visit, participants will receive balanced meals from the National Institutes of Health to consume for 2 days before the visit. During the scanning visit, participants will continue to eat the weight maintenance diet, complete questionnaires, and have a series of imaging studies (including positron emission tomography and magnetic resonance imaging tests) to evaluate brain response to food and other stimuli.

* Obese participants: Participants will be screened with a medical history, physical examination, blood and urine tests, and weight maintenance observations (food diaries and physical activity monitors). During the first inpatient visit, obese participants will eat a weight-maintenance diet for 5 days to establish baseline measurements. After several days of eating a weight-maintenance diet, 20 obese adult volunteers (BMI above 30 kg/m2) will be admitted to the metabolic clinical research unit (MCRU) and, after 5 additional days of the baseline diet, their diets will be modified to result in either 85% reduction of the baseline dietary fat or a 60% reduction of the baseline dietary carbohydrate for the next 6 days. These diet modifications produce an equivalent caloric reduction. The primary outcome measurements will be changes of metabolism, brain reward circuitry and regional brain activity in response to food stimuli measured during the baseline and reduced calorie diet phases. Immediately following each controlled diet, we will measure 3 days of ad-libitum food intake using a computerized vending machine system. The subjects will return to the MCRU after a 2-10 week washout period to receive the opposite reduced calorie diet. Twenty control subjects with normal body weight (BMI between 18.5 - 25 kg/m2) will have measurements of brain reward circuitry and regional brain activity in response to food stimuli while on a balanced, weight-maintenance diet. Immediately following the second in-patient visit, all of the obese subjects will be assigned to a 12 week out-patient weight loss program with the goal of achieving at least 5% weight loss. We will investigate the relationship between short-term fat imbalances measured during the in-patient phases, and the body weight and fat changes during the weight loss program. We will evaluate the effects of weight loss on metabolism, brain reward circuitry, and regional brain activity in response to food stimuli. Finally, if the subjects are available for long-term follow-up, then we will investigate their metabolic phenotype, brain reward circuitry, and regional brain activity in response to food stimuli yearly over the subsequent 5 years following the weight loss intervention. This study will result in an improved understanding of the physiological mechanisms that sense and respond to negative energy balance acutely, after several weeks, and after several years, and may eventually lead to increased long-term success of obesity treatment.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 43

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Obese RF then RC	Reduced fat diet	Obese adult volunteers (BMI above 30 kg/m2) randomized to receive an 85% reduction of baseline dietary fat (RF) for 2 weeks. After a washout period of 2 weeks, they then received a 60% reduction of baseline dietary carbohydrate (RC) for 2 weeks
Obese RF then RC	Reduced carbohydrate diet	Obese adult volunteers (BMI above 30 kg/m2) randomized to receive an 85% reduction of baseline dietary fat (RF) for 2 weeks. After a washout period of 2 weeks, they then received a 60% reduction of baseline dietary carbohydrate (RC) for 2 weeks
Obese RF then RC	fMRI	Obese adult volunteers (BMI above 30 kg/m2) randomized to receive an 85% reduction of baseline dietary fat (RF) for 2 weeks. After a washout period of 2 weeks, they then received a 60% reduction of baseline dietary carbohydrate (RC) for 2 weeks
Obese RF then RC	PET	Obese adult volunteers (BMI above 30 kg/m2) randomized to receive an 85% reduction of baseline dietary fat (RF) for 2 weeks. After a washout period of 2 weeks, they then received a 60% reduction of baseline dietary carbohydrate (RC) for 2 weeks
Obese RC then RF	Reduced fat diet	Obese adult volunteers (BMI above 30 kg/m2) randomized to receive a 60% reduction of baseline dietary carbohydrate (RC) for 2 weeks. After a washout period of 2 weeks, they then received an 85% reduction of baseline dietary fat (RF) for 2 weeks.
Obese RC then RF	Reduced carbohydrate diet	Obese adult volunteers (BMI above 30 kg/m2) randomized to receive a 60% reduction of baseline dietary carbohydrate (RC) for 2 weeks. After a washout period of 2 weeks, they then received an 85% reduction of baseline dietary fat (RF) for 2 weeks.
Obese RC then RF	fMRI	Obese adult volunteers (BMI above 30 kg/m2) randomized to receive a 60% reduction of baseline dietary carbohydrate (RC) for 2 weeks. After a washout period of 2 weeks, they then received an 85% reduction of baseline dietary fat (RF) for 2 weeks.
Obese RC then RF	PET	Obese adult volunteers (BMI above 30 kg/m2) randomized to receive a 60% reduction of baseline dietary carbohydrate (RC) for 2 weeks. After a washout period of 2 weeks, they then received an 85% reduction of baseline dietary fat (RF) for 2 weeks.
Lean Control	fMRI	Lean adult volunteers (BMI below 30kg/m2) placed on a weight-maintenance diet using a standard diet composition of 50% carbohydrate, 35% fat, and 15% protein on an out-patient basis
Lean Control	PET	Lean adult volunteers (BMI below 30kg/m2) placed on a weight-maintenance diet using a standard diet composition of 50% carbohydrate, 35% fat, and 15% protein on an out-patient basis

Primary Outcome Measures

Name	Time	Method
Change in Respiratory Quotient (RQ)	Baseline and day 14	Respiratory quotient was calculated as the ratio of carbon dioxide production to oxygen consumption as measured in a metabolic chamber for at least 23 continuous hours on days 2 and 5 of the baseline diet and days 1, 4, and 6 of the reduced-energy diets.

Secondary Outcome Measures

Name	Time	Method
Change in 24 Hour Energy Expenditure	Baseline and 14 days	24 hour energy expenditure was measured in a respiratory chamber.
Caudate Dopamine D2-like Receptor Binding Potential (D2BP)	Day 2 of in-patient admission	The time-activity curves for \[18F\]fallypride tracer concentration in the ROIs were measured by PET and kinetic parameters were fit to a four compartment mathematical model (with the cerebellum used as the reference tissue). D2BP was expressed as the dimensionless ratio of rate constants quantifying binding and unbinding of tracer in the regions of interest.
Putamen Dopamine D2-like Receptor Binding Potential (D2BP)	Day 2 of in-patient admission	The time-activity curves for \[18F\]fallypride tracer concentration in the ROIs were measured by PET and kinetic parameters were fit to a four compartment mathematical model (with the cerebellum used as the reference tissue). D2BP was expressed as the dimensionless ratio of rate constants quantifying binding and unbinding of tracer in the regions of interest.
Change in Cumulative Fat Imbalance	Baseline and 14 days	Measured as the difference between dietary fat intake and fat oxidation by the body as measured in the respiratory chamber
Accumbens Dopamine D2-like Receptor Binding Potential (D2BP)	Day 2 of in-patient admission	The time-activity curves for \[18F\]fallypride tracer concentration in the ROIs were measured by PET and kinetic parameters were fit to a four compartment mathematical model (with the cerebellum used as the reference tissue). D2BP was expressed as the dimensionless ratio of rate constants quantifying binding and unbinding of tracer in the regions of interest.