Study of the Effect of a Very-Low-Carbohydrate Diet on Energy Expenditure

Background:

- Popular weight loss plans often restrict carbohydrates or fat. Research shows that very-low-carbohydrate (ketogenic) diets lead to greater weight loss than low-fat diets. Researchers want to know if eating fewer carbohydrates changes the number of calories the body uses. They also want to know how a ketogenic diet affects hunger, hormones, and food preferences.

Objectives:

- To better understand how the body responds to different diets.

Eligibility:

- Men 18 to 50 years old who are healthy but overweight.

Design:

* Participants will have 3 screening visits:

  1. Medical history, physical exam, blood test, and EKG. They will eat during the visit.
  2. For the week before the visit, participants will wear physical activity monitors daily. They will record everything they eat and sample the special diet. At the visit, they will receive an EKG and heart rate test while biking for 30 minutes.
  3. For the week before the visit, participants will wear the physical activity monitors. They will eat all their meals from the special diet that will be provided. At the visit, they will answer questions and bike for 60 minutes.
* After screening, for 1 week, participants will visit the clinic daily to receive that day s food. They will not eat or drink anything else except water.
* Then participants will stay at the clinic for 8 weeks. They cannot leave but can have visitors. Participants will wear physical activity monitors, bike daily, and follow different diets. Tests will be given daily, and may include weighing, X-rays, and blood and urine tests. They will spend several days in a monitored room to test oxygen and carbon dioxide.

Popular weight loss strategies often prescribe targeted reduction of dietary carbohydrate or fat. Recent clinical trials in obese subjects have found that low-carbohydrate diets result in greater weight loss compared with low-fat diets on a time scale of months when diet adherence was likely the highest. One hypothesis regarding the mechanism of improved weight loss with low carbohydrate diets is that such diets significantly modify the body s hormonal milieu to influence metabolic regulation and energy expenditure. Low-carbohydrate diets may thereby offer a metabolic advantage over low fat diets. In addition, low-carbohydrate diets may also decrease hunger or increase satiety compared to low-fat diets.

Determining the mechanism whereby one diet leads to greater weight loss than another is hampered by the inability to accurately measure food intake or physical activity in an outpatient setting. Thus, an inpatient feeding study lasting many weeks is required to accurately measure energy balance differences between isocaloric diets that differ in macronutrient composition. In this pilot multicenter cross-over study in 16 overweight and class I obese men, we will measure changes in energy expenditure in response to 4 weeks of inpatient feeding of a eucaloric, very low carbohydrate, ketogenic diet (5% Carbohydrate, 15% Protein, 80% Fat) immediately following an inpatient period of at least 4 weeks of consuming an energy balanced standard American diet (50% Carbohydrate, 15 % Protein, 35% Fat).

Eligibility Criteria:
* INCLUSION CRITERIA:
* Age 18-50 years, male
* Weight stable (\< 5 % over past 6 months)
* Current stable weight no more than 8% below lifetime maximum weight
* Body mass index (BMI) greater than or equal to 25 kg/m(2) but less than 35 kg/m(2), with each study site recruiting an equal number of subjects from the overweight range of 25 kg/m(2) less than or equal to BMI \< 30 kg/m(2) and from the class I obese range of 30 kg/m(2) less than or equal to BMI \< 35 kg/m(2)
* Otherwise healthy, as determined by medical history and laboratory tests
* Able to complete daily bouts of stationary cycling at a moderate rate and intensity
* Written informed consent
* Willing to eat all the food provided in the study
* Willing to continue consistently their habitual caffeine intake

EXCLUSION CRITERIA:

* BMI \< 25 kg/m(2) or greater than or equal to 35 kg/m(2)
* Blood pressure \> 140/90 mm Hg
* Evidence of metabolic or cardiovascular disease, or disease that may influence metabolism (e.g. cancer, diabetes, thyroid disease)
* Taking any prescription medication or other drug that may influence metabolism (e.g. diet/weight-loss medication, asthma medication, blood pressure medication, psychiatric medications, corticosteroids, or other medications at the discretion of the PI and/or study team)
* Hematocrit \< 40%
* Participating in a regular exercise program (\> 2h/week of vigorous activity)
* Dietary carbohydrate less than 30% or greater than 65% of total calories as determined by food frequency questionnaire
* Caffeine consumption \> 300 mg/day
* Regular use of alcohol (\> 2 drinks per day), tobacco (smoking or chewing) amphetamines, cocaine, heroin, or marijuana over past 6 months
* Past or present history of eating disorder (including binge eating) or psychiatric disease, including claustrophobia since part of the protocol will involve being confined to a small room for whole-body indirect calorimetry
* Volunteers with strict dietary concerns (e.g. vegetarian or kosher diet, multiple food allergies)
* Volunteers unwilling or unable to give informed consent