The Effects of Increasing Caloric Intake on Diet-Induced Thermogenesis and 24h Energy Expenditure

Not Applicable

Recruiting

• Conditions: Healthy Volunteers; Normal Physiology; Obesity
• Interventions: Dietary Supplement: +200% of dietary requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat; Dietary Supplement: fasting; Dietary Supplement: -50% of energy balance requirements. 50% of calories from carbohydrates, 20% from protein, and 30% from fat; Dietary Supplement: +150% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat; Dietary Supplement: +200% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein; Dietary Supplement: -25% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat; Dietary Supplement: +150% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein

• Registration Number: NCT05545306
• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary

Background:

Diet-induced thermogenesis (DIT) is the amount of energy one s body uses to eat food, absorb the nutrients from the food, and process those nutrients. Researchers would like to understand more about how changing the balances of protein, fat, carbohydrates, and total calories in the diet can affect DIT.

Objective:

To learn how different diets can change a person s DIT.

Eligibility:

Healthy people aged 18 to 60 years who have not intentionally lost weight in the past 6 months.

Design:

Participants will stay in a clinic for about 34 days. They will eat only the food provided. They will receive 8 different diets during the study, including 7 test diets.

Participants will undergo multiple tests.

They will be screened with blood and urine tests and a test of their heart function.

During the first few days:

Their waist, thigh, and neck circumference will be measured.

They will have a DXA scan: They will lie on a padded table for about 20 minutes while an instrument measures the amount of fat in their body.

They will be tested for diabetes.

They will answer questionnaires about topics including eating behavior, hunger, and stress.

Throughout the study:

Their weight will be measured daily.

Blood tests will be repeated.

They will stay in a metabolic chamber a total of 9 times. They will remain in a closed room for 24 hours while researchers monitor the room temperature and levels of oxygen and carbon dioxide. Participants will collect all their urine for each 24-hour period.

...

Detailed Description

Study Description:

Diet-Induced Thermogenesis (DIT) has been reported to increase as a function of the amount caloric intake. This study investigated this dose response between calorie intake and energy expenditure using a single liquid meal. By measuring EE over 24 hours in our respiratory chamber, we can capture the full extent of DIT at different caloric doses in relation to energy balance. Furthermore, we will investigate inter-individual differences in 24hEE response to different calorie loads. This is important as our previous studies demonstrated that individuals with greater EE during energy balance have 1) greater decrease in EE to fasting and 2) blunted EE response to higher calorie loads, in particular those with low protein content, respectively. Briefly, we will make multiple measurements of 24h EE in a whole-room indirect calorimeter, the gold standard measure of metabolism at multiple levels of energy intake relative to energy balance. These measures will be done at energy balance and in random order during fasting, 25, 50, 150 and 200% of energy balance requirements. Macronutrient balance for energy balance and lower calorie diets will be 50% carbohydrate, 30% fat, 20% protein; but for overfeeding will be 3% protein, 46% fat, 51% carbohydrate. The main goals of this research are to examine using state of the art measurement of DIT in a respiratory chamber whether there is indeed an association between caloric intake and energy expenditure and whether inter-individual response to calorie loads differs such that those with higher 24hEE during energy balance, have lower 24hEE during fasting and underfeeding 25 and 50% and lesser response to high calorie loads.

The primary goal of this study is to investigate the impact of relative calorie load on diet-induced thermogenesis.

Objectives:

Primary Objective:

a. To determine whether an association exists between diet-induced thermogenesis, 24hEE and calorie load relative to energy balance.

Secondary Objectives:

1. To determine if participants with higher energy balance 24hEE adjusted for body composition, age, and sex have lower adjusted 24hEE to lower calorie loads (fasting, 25 and 50% of energy needs)

2. To determine if participants with higher energy balance 24h EE have lower adjusted 24hEE to high calorie loads with low protein overfeeding.

3. To assess changes in hormones known to be associated with changes in 24hEE (e.g., FGF21, ghrelin)

4. To assess changes in sympathetic nervous system activity based on changes in urinary catecholamines.

5. To assess changes in substrate oxidation rates at various dietary loads.

Tertiary/Exploratory Objectives:

1. To assess whether psychosocial differences are associated with 24hEE responses to calorie loads.

2. Although our analytic plan and data collection procedure are meant to be all encompassing and comprehensive, our central exploratory, tertiary objective is to perform additional secondary data analyses in the future that answer additional research questions regarding diabetes and obesity risk that were not discussed in primary and secondary endpoints. These additional aims include, but are not limited to, associations of metabolic measures with psychosocial measures, hormonal endpoints, or future biomarker assayed at a later time point.

Endpoints:

Primary Endpoint:

a. Diet induced thermogenesis, as calculated from 24h EE during feeding - 24h EE during fasting under different calorie loads

Secondary Endpoints:

1. 24-hour energy expenditure during low calorie loads

2. 24-hour energy expenditure at higher calorie loads with low protein calorie loads

3. 24-hour energy expenditure during higher calorie loads with standard macronutrient mixed

4. FGF-21, ghrelin, and other appetitive hormones

5. Urinary catecholamines

6. 24-hour respiratory quotient, protein, carbohydrate, and lipid oxidation.

Tertiary/Exploratory Endpoints:

a. Psychosocial assessments, such as food insecurity and perceived stress

Study Timeline

• Study First Submitted: 2022-09-16
• Study First Submitted QC: 2022-09-16
• Study First Posted: 2022-09-19
• Study Start: 2023-06-06
• Status Verified: 2025-04-22
• Last Update Submitted: 2025-04-23
• Last Update Posted: 2025-04-24
• Primary Completion: 2027-02-02
• Study Completion: 2027-02-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Set 6	fasting	Fasting +200% LPF +200% SOF -50% +150% LPF -25% +150% SOF
Set 6	+150% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	Fasting +200% LPF +200% SOF -50% +150% LPF -25% +150% SOF
Set 3	+200% of dietary requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% LPF Fasting +150% SOF -25% +200% SOF +200% LPF -50%
Set 7	+200% of dietary requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	-50% +200% SOF -25% +150% SOF Fasting +200% LPF +150% LPF
Set 7	fasting	-50% +200% SOF -25% +150% SOF Fasting +200% LPF +150% LPF
Set 1	+150% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% LPF +150% SOF -50% +200% LPF +200% SOF Fasting -25%
Set 1	+150% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	+150% LPF +150% SOF -50% +200% LPF +200% SOF Fasting -25%
Set 10	fasting	+200% LPF -25% Fasting +200% SOF -50% +150% LPF +150% SOF
Set 3	+150% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% LPF Fasting +150% SOF -25% +200% SOF +200% LPF -50%
Set 4	+200% of dietary requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	Fasting -25% +200% LPF -50% +200% SOF +150% SOF +150% LPF
Set 1	-25% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% LPF +150% SOF -50% +200% LPF +200% SOF Fasting -25%
Set 10	+150% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+200% LPF -25% Fasting +200% SOF -50% +150% LPF +150% SOF
Set 10	-25% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+200% LPF -25% Fasting +200% SOF -50% +150% LPF +150% SOF
Set 1	+200% of dietary requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% LPF +150% SOF -50% +200% LPF +200% SOF Fasting -25%
Set 1	fasting	+150% LPF +150% SOF -50% +200% LPF +200% SOF Fasting -25%
Set 1	+200% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	+150% LPF +150% SOF -50% +200% LPF +200% SOF Fasting -25%
Set 10	+150% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	+200% LPF -25% Fasting +200% SOF -50% +150% LPF +150% SOF
Set 2	-50% of energy balance requirements. 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% LPF +200% LPF -50% +150% SOF Fasting -25% +200% SOF
Set 1	-50% of energy balance requirements. 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% LPF +150% SOF -50% +200% LPF +200% SOF Fasting -25%
Set 10	+200% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	+200% LPF -25% Fasting +200% SOF -50% +150% LPF +150% SOF
Set 2	+150% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% LPF +200% LPF -50% +150% SOF Fasting -25% +200% SOF
Set 2	-25% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% LPF +200% LPF -50% +150% SOF Fasting -25% +200% SOF
Set 3	+200% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	+150% LPF Fasting +150% SOF -25% +200% SOF +200% LPF -50%
Set 3	+150% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	+150% LPF Fasting +150% SOF -25% +200% SOF +200% LPF -50%
Set 10	+200% of dietary requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+200% LPF -25% Fasting +200% SOF -50% +150% LPF +150% SOF
Set 10	-50% of energy balance requirements. 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+200% LPF -25% Fasting +200% SOF -50% +150% LPF +150% SOF
Set 2	+150% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	+150% LPF +200% LPF -50% +150% SOF Fasting -25% +200% SOF
Set 4	+150% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	Fasting -25% +200% LPF -50% +200% SOF +150% SOF +150% LPF
Set 5	fasting	-25% +150% SOF +200% LPF +150% LPF Fasting +200% SOF -50%
Set 5	+150% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	-25% +150% SOF +200% LPF +150% LPF Fasting +200% SOF -50%
Set 5	+200% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	-25% +150% SOF +200% LPF +150% LPF Fasting +200% SOF -50%
Set 5	-50% of energy balance requirements. 50% of calories from carbohydrates, 20% from protein, and 30% from fat	-25% +150% SOF +200% LPF +150% LPF Fasting +200% SOF -50%
Set 2	+200% of dietary requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% LPF +200% LPF -50% +150% SOF Fasting -25% +200% SOF
Set 2	fasting	+150% LPF +200% LPF -50% +150% SOF Fasting -25% +200% SOF
Set 2	+200% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	+150% LPF +200% LPF -50% +150% SOF Fasting -25% +200% SOF
Set 3	-50% of energy balance requirements. 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% LPF Fasting +150% SOF -25% +200% SOF +200% LPF -50%
Set 4	-50% of energy balance requirements. 50% of calories from carbohydrates, 20% from protein, and 30% from fat	Fasting -25% +200% LPF -50% +200% SOF +150% SOF +150% LPF
Set 4	+200% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	Fasting -25% +200% LPF -50% +200% SOF +150% SOF +150% LPF
Set 4	-25% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	Fasting -25% +200% LPF -50% +200% SOF +150% SOF +150% LPF
Set 5	+200% of dietary requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	-25% +150% SOF +200% LPF +150% LPF Fasting +200% SOF -50%
Set 3	fasting	+150% LPF Fasting +150% SOF -25% +200% SOF +200% LPF -50%
Set 3	-25% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% LPF Fasting +150% SOF -25% +200% SOF +200% LPF -50%
Set 4	fasting	Fasting -25% +200% LPF -50% +200% SOF +150% SOF +150% LPF
Set 4	+150% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	Fasting -25% +200% LPF -50% +200% SOF +150% SOF +150% LPF
Set 6	-50% of energy balance requirements. 50% of calories from carbohydrates, 20% from protein, and 30% from fat	Fasting +200% LPF +200% SOF -50% +150% LPF -25% +150% SOF
Set 8	+150% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	-50% +150% SOF +200% SOF +150% LPF -25% +200% LPF Fasting
Set 6	-25% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	Fasting +200% LPF +200% SOF -50% +150% LPF -25% +150% SOF
Set 7	+150% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	-50% +200% SOF -25% +150% SOF Fasting +200% LPF +150% LPF
Set 8	-25% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	-50% +150% SOF +200% SOF +150% LPF -25% +200% LPF Fasting
Set 5	-25% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	-25% +150% SOF +200% LPF +150% LPF Fasting +200% SOF -50%
Set 6	+200% of dietary requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	Fasting +200% LPF +200% SOF -50% +150% LPF -25% +150% SOF
Set 8	+150% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	-50% +150% SOF +200% SOF +150% LPF -25% +200% LPF Fasting
Set 9	-25% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% SOF -25% +150% LPF +200% SOF Fasting +200% LPF -50%
Set 5	+150% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	-25% +150% SOF +200% LPF +150% LPF Fasting +200% SOF -50%
Set 6	+150% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	Fasting +200% LPF +200% SOF -50% +150% LPF -25% +150% SOF
Set 6	+200% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	Fasting +200% LPF +200% SOF -50% +150% LPF -25% +150% SOF
Set 8	+200% of dietary requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	-50% +150% SOF +200% SOF +150% LPF -25% +200% LPF Fasting
Set 9	+200% of dietary requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% SOF -25% +150% LPF +200% SOF Fasting +200% LPF -50%
Set 7	+150% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	-50% +200% SOF -25% +150% SOF Fasting +200% LPF +150% LPF
Set 7	+200% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	-50% +200% SOF -25% +150% SOF Fasting +200% LPF +150% LPF
Set 7	-50% of energy balance requirements. 50% of calories from carbohydrates, 20% from protein, and 30% from fat	-50% +200% SOF -25% +150% SOF Fasting +200% LPF +150% LPF
Set 7	-25% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	-50% +200% SOF -25% +150% SOF Fasting +200% LPF +150% LPF
Set 8	fasting	-50% +150% SOF +200% SOF +150% LPF -25% +200% LPF Fasting
Set 9	fasting	+150% SOF -25% +150% LPF +200% SOF Fasting +200% LPF -50%
Set 9	+150% of energy balance requirements, 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% SOF -25% +150% LPF +200% SOF Fasting +200% LPF -50%
Set 9	+200% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	+150% SOF -25% +150% LPF +200% SOF Fasting +200% LPF -50%
Set 9	+150% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	+150% SOF -25% +150% LPF +200% SOF Fasting +200% LPF -50%
Set 8	-50% of energy balance requirements. 50% of calories from carbohydrates, 20% from protein, and 30% from fat	-50% +150% SOF +200% SOF +150% LPF -25% +200% LPF Fasting
Set 8	+200% of dietary requirements, 51% of the calories from carbohydrates, 46%, from fat and 3% from protein	-50% +150% SOF +200% SOF +150% LPF -25% +200% LPF Fasting
Set 9	-50% of energy balance requirements. 50% of calories from carbohydrates, 20% from protein, and 30% from fat	+150% SOF -25% +150% LPF +200% SOF Fasting +200% LPF -50%

Primary Outcome Measures

Name	Time	Method
Diet Induced Thermogenesis	35 days	DIT is calculated from 24h EE during feeding-24h EE during fasting under different caloric loads

Secondary Outcome Measures

Name	Time	Method
FGF 21	35 days	assessment of appetitive hormones before and after 24h in a whole room calorimeter with each intervention
24 hour energy expenditure (24h EE)	35 days	24h EE is measured in a whole room calorimeter
Substrate Oxidation	35 days	24h respiratory quotient measured in a whole room calorimeter
Psychosocial Assessment	35 days	assessment of psychosocial state through assessment of food insecurity and perceived stress
Ghrelin	35 days	assessment of appetitive hormones before and after 24h in a whole room calorimeter with each intervention
Sympathetic nervous system activity	35 days	assessment of changes in urinary catecholamines with each intervention

Trial Locations

Locations (1)

NIDDK, Phoenix; 🇺🇸 Phoenix, Arizona, United States