NCT00846040

Reduced Carbohydrate Versus Fat in Obese Subjects

Selective Reduction of Dietary Carbohydrate Versus Fat: Effects on Metabolism, Endocrine Physiology, Brain Activity and Reward Circuitry

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · NIH
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Obesity

Interventions

Type	Name	Description
OTHER	Reduced fat diet	RF (selective reduction of 85% of baseline fat calories per day)
OTHER	Reduced carbohydrate diet	RC (selective reduction of 60% of baseline carbohydrate calories per day)
DRUG	Drug: f-18 fallypride	Dopamine D2 receptor availability is measured by positron emission tomography (PET) using the positron emitting compound \[18F\] fallypride which binds competitively with dopamine to the D2 receptor.
DEVICE	fMRI	Functional MRI (fMRI) will be used to measure the effects of diet and weight loss on regional brain activity
DEVICE	PET	Positron emission tomography (PET) will be used to assess whether To assess whether brain activity and reward pathways are altered

Timeline

• Start date: 2009-02-13
• Primary completion: 2014-02-24
• Completion: 2014-10-20
• First posted: 2009-02-18
• Last updated: 2021-04-15
• Results posted: 2021-03-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study