Diet Order Effects of Low Fat vs. Low Carb Diets on Body Fat Change

NCT ID: NCT06325722

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-28
• Study Completion Date: 2026-07-31

Brief Summary

Background:

In a previous study, participants were lived at the NIH and randomly received either a low-fat or a low-carbohydrate diet for 2 weeks and then switched to the other diet for 2 more weeks. Participants who received the low-carbohydrate diet first lost more body fat at the end of the study than those who received the low-fat diet first. Researchers want to see if they can repeat that result in a longer weight loss study when participants live at home.

Objective:

To test the effects of diet order in people receiving either a low-fat or low-carbohydrate diet first for 4 weeks and then immediately switched to the other diet for another 4 weeks.

Eligibility:

Adults aged 19 to 50 years with a body mass index of 25 or more.

Design:

Participants will complete the study at their homes, but there will be 3 required visits to the NIH. Participants will drink a special type of water 2 weeks before the baseline NIH visit and collect urine samples at home to measure how many calories they burn. Before the diets begin, participants will visit the NIH for baseline testing when they will have a metabolism test while relaxing in a bed with a plastic hood over their head to collect the air they breathe out. They will have scans to measure their bone density and how much muscle and body fat they have. They will give stool, blood, and urine samples.

Participants will be asked to eat a specific diet for 4 weeks followed by a different diet for 4 weeks. All meals will be delivered to the participants' homes. They will eat only the foods delivered.

Participants will weigh themselves daily. They will wear a monitor to track their physical activity and a sensor to measure their glucose levels. They will prick their finger each morning to test a drop of blood for ketones. Participants will meet virtually as a group with the study team weekly. Participants will have two more NIH visits towards the end of each diet period....

Detailed Description

Study Description:

This is an 8-week crossover outpatient feeding trial of a low carbohydrate versus a low-fat diet, each provided for 4 weeks in random order with no washout period, in adult volunteers with overweight or obesity.

Objectives:

Primary Objectives: To determine the effect of diet order on the mean total fat mass change in subjects randomized to receive either a low carbohydrate followed by a low fat diet or the reverse order, with each diet lasting for 4 weeks.

Secondary Objectives: To determine the effect of diet order on the mean rate of body weight change in subjects randomized to receive either a low carbohydrate followed by a low fat diet or the reverse order, with each diet lasting for 4 weeks and the rate of weight change is measured during the last 2 weeks of each diet. To determine the effect of diet order on mean total body weight change in subjects randomized to receive either a low carbohydrate followed by a low fat diet or the reverse order, with each diet lasting for 4 weeks.

Endpoints:

Primary Endpoint: Mean total fat mass change measured by dual energy X-ray absorptiometry at baseline and week 8.

Secondary Endpoints: Mean rate of weight change by linear mixed modeling of daily weight measurements. Mean total body weight change measured between baseline and week 8.

Conditions

Overweight; Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

low-carbohydrate diet then low-fat diet

A low-carbohydrate followed by low-fat diet, each lasting for 4 weeks in adults with overweight or obesity

Group Type: EXPERIMENTAL

Low-carbohydrate Diet

Intervention Type: OTHER

Consisting of 15 percent protein, 75 percent fat, and 10 percent carbohydrate

Low-fat Diet

Intervention Type: OTHER

Consisting of 15 percent protein, 10 percent fat, and 75 percent carbohydrate

low-fat diet then low-carbohydrate diet

A low-fat followed by low-carbohydrate diet, each lasting for 4 weeks in adults with overweight or obesity

Group Type: EXPERIMENTAL

Low-carbohydrate Diet

Intervention Type: OTHER

Consisting of 15 percent protein, 75 percent fat, and 10 percent carbohydrate

Low-fat Diet

Intervention Type: OTHER

Consisting of 15 percent protein, 10 percent fat, and 75 percent carbohydrate

Interventions

Low-carbohydrate Diet

Consisting of 15 percent protein, 75 percent fat, and 10 percent carbohydrate

Intervention Type: OTHER

Low-fat Diet

Consisting of 15 percent protein, 10 percent fat, and 75 percent carbohydrate

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Stated willingness to comply with all study procedures and availability for the duration of the study

2. Adults aged 18-50 years

3. Weight stable (< +/- 5 percent over past 6 months) as determined by volunteer report

4. Body mass index (BMI) >= 25 kg/m^2

5. Agreement to adhere to Lifestyle Considerations throughout the study duration

Exclusion Criteria

1. Subjects with cardiac pacemakers or other implants that may be affected by or affect the DXA measurements

2. Inadequate access to equipment required for the study (e.g., too little refrigerator storage space or a microwave oven that is too small) as determined by discretion of PI and/or study team

3. Evidence of diseases or conditions that may influence appetite (e.g., cancer, diabetes, alterations of smell or taste post COVID-19), diseases or conditions that affect the immune system, or other conditions at the discretion of the PI and/or study team

4. Taking prescription medications or other drugs that may influence metabolism (including but not limited to diet/weight-loss medication, some psychiatric medications, or other medications at the discretion of the PI and/or study team)

5. People unlikely to adhere to a relatively consistent daily and weekly routine and avoid travel during their participation in the study. For example, people with occupations such as pilots, flight attendants, or frequently travel for work or pleasure.

6. People unlikely to abstain from off study food or supplements that may impact metabolism or appetite at the discretion of the study team

7. Positive pregnancy test or lactating as determined by volunteer report (women only)

8. Inability or unwillingness to use birth control between screening and completion of the study (women only)

9. Symptoms or signs of perimenopause or menopause by volunteer report (women only)

10. Regular vigorous exercise >150 min per week as determined by volunteer report

11. Alcohol consumption > 3 drinks per day as determined by volunteer report

12. Regular use of tobacco (smoking, chewing, or vaping), nicotine replacement therapy, or illicit drugs over past 6 months as determined by volunteer report. Subjects may also be excluded based on a urine drug test.

13. Psychological conditions as determined by DSM-5 Self-rated Level 1 Cross-cutting Symptom Measure such as (but not limited to) eating disorders, depression, bipolar disorders, that would be incompatible with safe and successful participation in this study, as determined by investigators

14. Volunteers with strict dietary concerns (e.g. vegetarian or kosher diet, food allergies) or a reported dislike of a significant fraction of the study foods

15. Volunteers unwilling or unable to give informed consent

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Valerie L Darcey

Role: PRINCIPAL_INVESTIGATOR

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

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Nan Zhai, C.R.N.P.

Role: CONTACT

nan.zhai@nih.gov

(301) 827-3324

Valerie L Darcey

Role: CONTACT

valerie.darcey@nih.gov

(301) 402-9689

Facility Contacts

Valerie Darcey

Role: primary

valerie.darcey@nih.gov

301-402-9689

References

Sciarrillo CM, Guo J, Hengist A, Darcey VL, Hall KD. Diet order affects energy balance in randomized crossover feeding studies that vary in macronutrients but not ultra-processing. medRxiv [Preprint]. 2023 Oct 4:2023.10.03.23296501. doi: 10.1101/2023.10.03.23296501.

Reference Type: BACKGROUND

PMID: 37986904 (View on PubMed)

Hall KD, Guo J, Courville AB, Boring J, Brychta R, Chen KY, Darcey V, Forde CG, Gharib AM, Gallagher I, Howard R, Joseph PV, Milley L, Ouwerkerk R, Raisinger K, Rozga I, Schick A, Stagliano M, Torres S, Walter M, Walter P, Yang S, Chung ST. Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake. Nat Med. 2021 Feb;27(2):344-353. doi: 10.1038/s41591-020-01209-1. Epub 2021 Jan 21.

Reference Type: BACKGROUND

PMID: 33479499 (View on PubMed)

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_001680-DK.html

NIH Clinical Center Detailed Web Page

Other Identifiers

001680-DK

Identifier Type: -

Identifier Source: secondary_id

10001680

Identifier Type: -

Identifier Source: org_study_id