Effects of Low Fat Versus Low Carbohydrate Diets on Energy Metabolism

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT03878108
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arms: 2
• Actual Duration (Months): 16.6
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

Background:

Researchers want to learn how different diets affect hormone levels, body weight, energy expenditure, liver fat, and more. To do this, they will use specialized techniques and food plans. This is not a weight loss study.

Objective:

To better understand how low-fat and low-carbohydrate foods affect health.

Eligibility:

Men and women ages 18-50 who have a stable body weight and can exercise daily

Design:

Participants will have a screening visit that lasts 4-6 hours. It will include:

Medical history

Physical exam

Fasting blood and urine tests

Questionnaires

Trying foods from the study

Participants will be admitted to the Clinical Center and will stay for 4 weeks without leaving. They can have visitors.

Participants will wear activity and glucose monitors throughout the study. They will be weighed daily and will complete daily exercise. They will eat 3 meals daily, plus snacks. They will give urine, saliva, and blood samples. They will fill out questionnaires and rate their hunger, appetite, and sense of taste. They will have body scans. For the scans, they will lie in a machine that takes X-ray pictures of the body.

Participants will complete activities to measure how many calories they burn and how the diets affect them:

Participants will drink special liquids to measure calories burned, sugar, and sense of taste.

Participants will wear a plastic hood while resting.

Participants will stay alone in a special room for 24 hours.

Participants will eat a low-carb, high-fat diet for 2 weeks and a high-carb, low-fat diet for 2 weeks.

Participants may be dismissed if they purposefully use the study to try to change their body weight.

Sponsoring Institution: National Institute of Diabetes and Digestive and Kidney Diseases

...

Condition or Disease	Intervention/Treatment	Phase
Healthy; Healthy Volunteers	Dietary Supplement: LCHF diet; Dietary Supplement: LFHC diet	N/A

Detailed Description

Competing theories about obesity and its treatment contrast the relative roles of dietary fat versus carbohydrate on promotion of excessive calorie intake. Advocates of low-carbohydrate diets propose that diets high in carbohydrates lead to elevated insulin secretion and increased calorie intake. Alternatively, proponents of low-fat diets argue that diets high in fat promote passive overconsumption due to the high energy density and low satiety index of high-fat foods. Therefore, we will conduct a feeding study in 20 adult men and women to investigate the differences in ad libitum energy intake resulting from consuming two test diets for a pair of 2-week periods in a randomized, crossover design during a single 4-week inpatient period. The test diets presented to participants will be matched for calories and protein, but the low-carbohydrate diet (approximately10% of calories) will be high in fat (approximately75% of calories) whereas the low-fat diet will be high in carbohydrates (approximately75% of calories) and low in fat (approximately 10% of calories).

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effect of Low Fat Versus Low Carbohydrate Diets on Energy Metabolism
• Actual Study Start Date: Apr 15, 2019
• Actual Primary Completion Date: Mar 4, 2020
• Actual Study Completion Date: Sep 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: LCHF diet then LFHC diet Low carbohydrate, high fat (LCHF) diet then low fat, high carbohydrate diet (LFHC) diet	Dietary Supplement: LCHF diet; low-carbohydrate, high-fat (LCHF)diet; Dietary Supplement: LFHC diet; low-fat, high-carbohydrate (LFHC) diet
Active Comparator: LFHC diet then LCHF diet Low fat, high carbohydrate diet (LFHC) diet then low carbohydrate, high fat (LCHF) diet	Dietary Supplement: LCHF diet; low-carbohydrate, high-fat (LCHF)diet; Dietary Supplement: LFHC diet; low-fat, high-carbohydrate (LFHC) diet

Outcome Measures

Primary Outcome Measures

1. Ad Libitum Energy Intake [14 days]

   Ad libitum energy intake averaged over 14 days for each diet, measured in kilocalories (kcal) per day.

Secondary Outcome Measures

1. Mean Glucose During Oral Glucose Tolerance Test (OGTT) [Day 14]

   An OGTT was performed at the end of each 14 day period and the mean glucose was calculated

2. Change in Body Weight [Baseline and day 14]

   Change in body weight from baseline to day 14 for each diet, measured in kilograms (kg)

3. Change in Body Fat Mass [Baseline and day 14]

   Change in body fat mass from baseline to day 14 for each diet, measured in kilograms (kg). Body fat mass was measured using Dual-energy X-ray absorptiometry (DXA) measurements.

4. Change in Cholesterol [Baseline and day 14]

   Change in cholesterol from baseline to day 14 for each diet

5. Change in Triglycerides [Baseline and day 14]

   Change in triglycerides from baseline to day 14 for each diet

6. Change in TSH [Baseline and day 14]

   Change in thyroid stimulating hormone (TSH) from baseline to day 14 for each diet

7. Change in C-peptide [Baseline and day 14]

   Change in C-peptide from baseline to day 14 for each diet

8. Change in CRP [Baseline and day 14]

   Change in C-reactive protein (CRP) from baseline to day 14 for each diet

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

• INCLUSION CRITERIA:

1. Adults age 18-50 years, male and female

2. Weight stable (less than or equal to 5 % over past 6 months) as determined by volunteer report

3. Body mass index (BMI) greater that or equal to 20kg/m2

4. Body weight greater than or equal to 53 kg

5. Able to complete daily bouts of stationary cycling at a moderate rate and intensity with a heart rate (HR) equal to or greater than 0.3(SqrRoot) (220-age-HRrest)+HRrest but not exceeding 0.4(SqrRoot) (220-age-HRrest)+HRrest and no signs of arrhythmia

EXCLUSION CRITERIA:

1. Evidence of metabolic or cardiovascular disease, or disease that may influence metabolism (e.g. cancer, diabetes, thyroid disease)

2. 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)

3. Positive pregnancy test or lactation as determined by volunteer report (women only)

4. Participating in a regular exercise program (> 2h/week of vigorous activity) as determined by volunteer report

5. Hematocrit <37% (women only)

6. Hematocrit < 40% (men only)

7. Caffeine consumption > 300 mg/day as determined by volunteer report

8. Regular use of alcohol (> 2 drinks per day), tobacco (smoking or chewing) amphetamines, cocaine, heroin, or marijuana over past 6 months as determined by volunteer report

9. Psychological conditions such as (but not limited to) eating disorders, claustrophobia, clinical depression, bipolar disorders, that would be incompatible with safe and successful participation in this study, as determined by investigators.

10. Past or present history of eating disorders as determined by volunteer report

11. Past or present history of claustrophobia since part of the protocol will involve being confined to a small room for whole-body indirect calorimetry and being in an MRI scanner for liver fat measures

12. Implants, devices, or foreign objects implanted in the body that interfere with the Magnetic Resonance procedures

13. Volunteers with strict dietary concerns (e.g. vegetarian or kosher diet, food allergies)

14. Volunteers unwilling or unable to give informed consent

15. Non-English speakers due to unavailability of required questionnaires in other languages

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Kevin Hall, Ph.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 28, 2020

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

None provided.

• Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• ClinicalTrials.gov Identifier: NCT03878108
• Other Study ID Numbers: 190067; 19-DK-0067
• First Posted: Mar 18, 2019
• Last Update Posted: Jun 3, 2021
• Last Verified: Dec 4, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): Accelerometry; Body Composition; Body Weight Regulation; Calories; Energy Expenditure

Study Results

Participant Flow

Arm/Group Title	LCHF Diet Then LFHC Diet	LFHC Diet Then LCHF Diet
Arm/Group Description	Low carbohydrate, high fat (LCHF) diet then low fat, high carbohydrate diet (LFHC) diet	Low fat, high carbohydrate diet (LFHC) diet then low carbohydrate, high fat (LCHF) diet
Period Title: Overall Study
STARTED	11	10
Completed First Phase	10	10
COMPLETED	10	10
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	LCHF Diet Then LFHC Diet	LFHC Diet Then LCHF Diet	Total
Arm/Group Description	Low carbohydrate, high fat (LCHF) diet then low fat, high carbohydrate diet (LFHC) diet	Low fat, high carbohydrate diet (LFHC) diet then low carbohydrate, high fat (LCHF) diet	Total of all reporting groups
Overall Participants	11	10	21
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	28.7 (7.1)	31.6 (5.5)	30.1 (6.4)
Sex: Female, Male (Count of Participants)
Female	5 45.5%	4 40%	9 42.9%
Male	6 54.5%	6 60%	12 57.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 18.2%	2 20%	4 19%
Not Hispanic or Latino	9 81.8%	8 80%	17 81%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 9.1%	1 10%	2 9.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 36.4%	4 40%	8 38.1%
White	5 45.5%	5 50%	10 47.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 9.1%	0 0%	1 4.8%
Region of Enrollment (participants) [Number]
United States	11 100%	10 100%	21 100%

Outcome Measures

1. Primary Outcome

Title	Ad Libitum Energy Intake
Description	Ad libitum energy intake averaged over 14 days for each diet, measured in kilocalories (kcal) per day.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LC Diet	LF Diet
Arm/Group Description	Low carbohydrate diet	Low fat diet
Measure Participants	20	20
Mean (Standard Error) [kcal per day]	2752 (52.0)	2063 (52.0)

2. Secondary Outcome

Title	Mean Glucose During Oral Glucose Tolerance Test (OGTT)
Description	An OGTT was performed at the end of each 14 day period and the mean glucose was calculated
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LC Diet	LF Diet
Arm/Group Description	Low carbohydrate diet	Low fat diet
Measure Participants	20	20
Mean (Standard Error) [mg/dl]	115.6 (2.9)	143.3 (2.9)

3. Secondary Outcome

Title	Change in Body Weight
Description	Change in body weight from baseline to day 14 for each diet, measured in kilograms (kg)
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LC Diet	LF Diet
Arm/Group Description	Low carbohydrate diet	Low fat diet
Measure Participants	20	20
Mean (Standard Error) [kg]	1.77 (0.32)	1.09 (0.32)

4. Secondary Outcome

Title	Change in Body Fat Mass
Description	Change in body fat mass from baseline to day 14 for each diet, measured in kilograms (kg). Body fat mass was measured using Dual-energy X-ray absorptiometry (DXA) measurements.
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LC Diet	LF Diet
Arm/Group Description	Low carbohydrate diet	Low fat diet
Measure Participants	20	20
Mean (Standard Error) [kg]	-0.18 (0.19)	-0.67 (0.19)

5. Secondary Outcome

Title	Change in Cholesterol
Description	Change in cholesterol from baseline to day 14 for each diet
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LC Diet	LF Diet
Arm/Group Description	Low carbohydrate diet	Low fat diet
Measure Participants	20	20
Mean (Standard Error) [mg/dl]	-1.25 (5.47)	-41.75 (5.47)

6. Secondary Outcome

Title	Change in Triglycerides
Description	Change in triglycerides from baseline to day 14 for each diet
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LC Diet	LF Diet
Arm/Group Description	Low carbohydrate diet	Low fat diet
Measure Participants	20	20
Mean (Standard Error) [mg/dl]	-12.1 (6.4)	17.9 (6.4)

7. Secondary Outcome

Title	Change in TSH
Description	Change in thyroid stimulating hormone (TSH) from baseline to day 14 for each diet
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LC Diet	LF Diet
Arm/Group Description	Low carbohydrate diet	Low fat diet
Measure Participants	20	20
Mean (Standard Error) [uIU/ml]	0.082 (0.176)	-0.403 (0.176)

8. Secondary Outcome

Title	Change in C-peptide
Description	Change in C-peptide from baseline to day 14 for each diet
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LC Diet	LF Diet
Arm/Group Description	Low carbohydrate diet	Low fat diet
Measure Participants	20	20
Mean (Standard Error) [ng/ml]	-0.610 (0.080)	-0.250 (0.080)

9. Secondary Outcome

Title	Change in CRP
Description	Change in C-reactive protein (CRP) from baseline to day 14 for each diet
Time Frame	Baseline and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LC Diet	LF Diet
Arm/Group Description	Low carbohydrate diet	Low fat diet
Measure Participants	16	15
Mean (Standard Error) [mg/l]	0.068 (0.289)	-0.842 (0.296)

Adverse Events

Time Frame	During each 14 day diet period
Arm/Group Title	LC Diet		LF Diet
Arm/Group Description	Low carbohydrate diet		Low fat diet
All Cause Mortality
	LC Diet		LF Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/20 (0%)
Serious Adverse Events
	LC Diet		LF Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	LC Diet		LF Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/21 (4.8%)		0/20 (0%)
Metabolism and nutrition disorders
Hypoglycemia	1/21 (4.8%)	1	0/20 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.