Clinical trial NCT01967563: Study of the Effect of a Very-Low-Carbohydrate Diet on Energy Expenditure
Official title: Effect of a Eucaloric Ketogenic Diet on Energy Expenditure: A Pilot Study
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Obesity
Appetite
Healthy Volunteers
Keywords: Energy Expenditure
Obesity
Carbohydrate
Fat
Ketones
Natural History
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: Pennington Biological Research Center
name: Translational Research Institute for Metabolism and Diabetes
name: Columbia University, New York, NY
First posted: 2013-10-23
Enrollment: 5
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: We will study the magnitude and variability of energy expenditure changes in response to a eucaloric ketogenic diet subsequent to a standard energy- and macronutrient-balanced diet in overweight and class I obese adult male volunteers

Brief summary: 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.

Detailed description: 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

Primary outcomes:
measure: To determine 24hr energy expenditure, respiratory quotient, and sleeping energy expenditure following a 4-week eucaloric ketogenic diet as compared to 4 weeks of consuming an energy-balanced standard diet.
timeFrame: 1 year
Secondary outcomes:
measure: To investigate changes in body composition and appetitive behaviors such as hunger, satiety, food impulsivity, and food liking &amp; wanting during a 4-week eucaloric ketogenic diet as compared to 4 weeks of consuming an energy-balanced stan...
timeFrame: 7 days(outpatient) plus 8 weeks( inpatient)
measure: To determine body weight and body composition following a 4-week eucaloric ketogenic diet as compared to 4 weeks of consuming an energy-balanced standard diet.
timeFrame: 7 days (outpatient) plus 8 weeks (inpatient)
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Kevin Hall, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rosenbaum M, Hall KD, Guo J, Ravussin E, Mayer LS, Reitman ML, Smith SR, Walsh BT, Leibel RL. Glucose and Lipid Homeostasis and Inflammation in Humans Following an Isocaloric Ketogenic Diet. Obesity (Silver Spring). 2019 Jun;27(6):971-981. doi: 10.1002/oby.22468. Epub 2019 May 8.
citation: Hall KD, Guo J, Chen KY, Leibel RL, Reitman ML, Rosenbaum M, Smith SR, Ravussin E. Methodologic considerations for measuring energy expenditure differences between diets varying in carbohydrate using the doubly labeled water method. Am J Clin Nutr. 2019 May 1;109(5):1328-1334. doi: 10.1093/ajcn/nqy390.
citation: Koppel N, Bisanz JE, Pandelia ME, Turnbaugh PJ, Balskus EP. Discovery and characterization of a prevalent human gut bacterial enzyme sufficient for the inactivation of a family of plant toxins. Elife. 2018 May 15;7:e33953. doi: 10.7554/eLife.33953.
citation: Hall KD, Chen KY, Guo J, Lam YY, Leibel RL, Mayer LE, Reitman ML, Rosenbaum M, Smith SR, Walsh BT, Ravussin E. Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men. Am J Clin Nutr. 2016 Aug;104(2):324-33. doi: 10.3945/ajcn.116.133561. Epub 2016 Jul 6.