Effect of Ultra Processed Versus Unprocessed Diets on Energy Intake

NCT03407053 | Completed Results

• 2 other identifiers: 18004418-DK-0044
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Eating too much processed food is believed to lead to obesity. But the effect of processed food on energy intake has not been carefully studied. Researchers want to study people s diets for 4 weeks and do specialized tests of the effects. Participants will get two diets. They will have the same calories and nutrients, but one diet will be unprocessed food and the other will be ultra-processed. Objective: To better understand how processed and unprocessed foods affect daily food consumption and how the body handles blood sugar. Eligibility: Healthy adults ages 18-50 who have stable weight and can exercise Design: Participants will not eat for 12 hours. Then they will be screened with:

• Medical history
• Physical exam
• Heart and blood tests
• Resting energy expenditure test (REE). A hood will collect air exhaled while lying down for 30-40 minutes.
• Psychiatric questions
• Questions about mood, eating, sleep, and socioeconomic status
• 20-minute stationary biking Female participants will have a urine pregnancy test. Participants will stay in the clinic for 4 weeks. For 2 weeks they will get a processed diet. For the other 2 weeks they will get an unprocessed diet. Participants cannot use the study period to gain or lose weight. Participants will have:
• Meals and snacks provided
• Daily exercise
• Blood, urine, and saliva tests
• To drink a special water and a very sweet liquid
• REE
• Scans and X-rays
• To wear activity monitors and a device to measure blood sugar
• Several 24-hour periods in a room that measures oxygen and carbon dioxide
• Repeats of screening questions
• Questions about hunger and meals
• Sleep monitoring
• Taste tests

Conditions

Healthy Diet

Keywords

Calories; Food Intake; Glucose; Body Composition; Body Weight Regulation

Outcome Measures

Primary Outcomes (1)

• Ad Libitum Energy Intake

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

  14 days

Secondary Outcomes (2)

• Change in Body Weight

  Baseline and day 14

• Change in Fat Mass

  Baseline and day 14

Study Arms (2)

Ultra-processed diet then unprocessed diet

ACTIVE COMPARATOR

Participants assigned to this arm will consume ultra-processed diet for two weeks followed by unprocessed diet for two weeks

Dietary Supplement: Ultra-processed diet; Dietary Supplement: Unprocessed diet

Unprocessed diet then ultra-processed diet

ACTIVE COMPARATOR

Participants assigned to this arm will consume unprocessed diet for two weeks followed by ultra-processed diet for two weeks

Dietary Supplement: Ultra-processed diet; Dietary Supplement: Unprocessed diet

Interventions

Ultra-processed diet DIETARY_SUPPLEMENT

Consuming ultra-processed diet over a 2-week period

Ultra-processed diet then unprocessed diet; Unprocessed diet then ultra-processed diet

Unprocessed diet DIETARY_SUPPLEMENT

Consuming unprocessed diet over a 2-week period

Ultra-processed diet then unprocessed diet; Unprocessed diet then ultra-processed diet

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults age 18-50 years, male and female
• Weight stable (\< +/- 5 % over past 6 months)
• \. Body mass index (BMI) greater than or equal to 18 kg/m\^2
• \. Willing to cease their habitual caffeine intake during the study, beginning one week prior to inpatient admission
• \. Written informed consent
• \. Willing to eat the food provided in the study
• \. Able to complete daily bouts of stationary cycling at a moderate rate and intensity with a heart rate (HR) equal to or greater than 0.3x(220-age-HR(rest))+HR(rest) but not exceeding 0.4x(220-age-HR(rest))+HR(rest) and no signs of arrhythmia

You may not qualify if:

• 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 \< 34% (women only)
• Hematocrit \< 40% (men only)
• Pregnancy, lactation (women only)
• Participating in a regular exercise program (\> 2h/week of vigorous activity)
• 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
• Eating disorders or psychological conditions, such as (but not limited to) claustrophobia, clinical depression, bi-polar disorders, that would be incompatible with safe and successful participation in this study, as determined by investigators.
• 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
• Implants, devices, or foreign objects implanted in the body that interfere with the Magnetic Resonance procedures
• Volunteers with strict dietary concerns (e.g. vegetarian or kosher diet, food allergies)
• Volunteers unwilling or unable to give informed consent
• Non-English speakers due to unavailability of required questionnaires in other languages.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (9)

• Hall KD, Ayuketah A, Brychta R, Cai H, Cassimatis T, Chen KY, Chung ST, Costa E, Courville A, Darcey V, Fletcher LA, Forde CG, Gharib AM, Guo J, Howard R, Joseph PV, McGehee S, Ouwerkerk R, Raisinger K, Rozga I, Stagliano M, Walter M, Walter PJ, Yang S, Zhou M. Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake. Cell Metab. 2019 Jul 2;30(1):67-77.e3. doi: 10.1016/j.cmet.2019.05.008. Epub 2019 May 16.

  PMID: 31105044 RESULT

• Brunstrom JM, Schatzker M, Rogers PJ, Courville AB, Hall KD, Flynn AN. Consuming an unprocessed diet reduces energy intake: a post-hoc analysis of an randomized controlled trial reveals a role for human "nutritional intelligence". Am J Clin Nutr. 2025 Dec 29:101183. doi: 10.1016/j.ajcnut.2025.101183. Online ahead of print.

  PMID: 41475551 DERIVED

• Abar L, Steele EM, Lee SK, Kahle L, Moore SC, Watts E, O'Connell CP, Matthews CE, Herrick KA, Hall KD, O'Connor LE, Freedman ND, Sinha R, Hong HG, Loftfield E. Identification and validation of poly-metabolite scores for diets high in ultra-processed food: An observational study and post-hoc randomized controlled crossover-feeding trial. PLoS Med. 2025 May 20;22(5):e1004560. doi: 10.1371/journal.pmed.1004560. eCollection 2025 May.

  PMID: 40392756 DERIVED

• Hengist A, Ong JA, McNeel K, Guo J, Hall KD. Imprecision nutrition? Intraindividual variability of glucose responses to duplicate presented meals in adults without diabetes. Am J Clin Nutr. 2025 Jan;121(1):74-82. doi: 10.1016/j.ajcnut.2024.10.007. Epub 2024 Dec 2.

  PMID: 39755436 DERIVED

• Sciarrillo CM, Guo J, Hengist A, Darcey VL, Hall KD. Diet order significantly affects energy balance for diets varying in macronutrients but not ultraprocessing in crossover studies without a washout period. Am J Clin Nutr. 2024 Oct;120(4):953-963. doi: 10.1016/j.ajcnut.2024.08.013. Epub 2024 Aug 18.

  PMID: 39163976 DERIVED

• 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.

  PMID: 37986904 DERIVED

• O'Connor LE, Hall KD, Herrick KA, Reedy J, Chung ST, Stagliano M, Courville AB, Sinha R, Freedman ND, Hong HG, Albert PS, Loftfield E. Metabolomic Profiling of an Ultraprocessed Dietary Pattern in a Domiciled Randomized Controlled Crossover Feeding Trial. J Nutr. 2023 Aug;153(8):2181-2192. doi: 10.1016/j.tjnut.2023.06.003. Epub 2023 Jun 3.

  PMID: 37276937 DERIVED

• Jaime-Lara RB, Franks AT, Agarwal K, Nawal N, Courville AB, Guo J, Yang S, Brooks BE, Roy A, Taylor K, Darcey VL, LeCheminant JD, Chung S, Forde CG, Hall KD, Joseph PV. No significant salt or sweet taste preference or sensitivity differences following ad libitum consumption of ultra-processed and unprocessed diets: a randomized controlled pilot study. Chem Senses. 2023 Jan 1;48:bjad007. doi: 10.1093/chemse/bjad007.

  PMID: 36897799 DERIVED

• Howard R, Guo J, Hall KD. Imprecision nutrition? Different simultaneous continuous glucose monitors provide discordant meal rankings for incremental postprandial glucose in subjects without diabetes. Am J Clin Nutr. 2020 Oct 1;112(4):1114-1119. doi: 10.1093/ajcn/nqaa198.

  PMID: 32766882 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

Results Point of Contact

• Title: Kevin Hall, PhD
• Organization: NIDDK

kevin.hall@nih.gov

301-402-8248

Study Officials

• Kevin Hall, Ph.D.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2018
• First Posted: January 23, 2018
• Study Start: March 1, 2018
• Primary Completion: February 26, 2020
• Study Completion: February 26, 2020
• Last Updated: June 29, 2021
• Results First Posted: June 29, 2021

Record last verified: 2021-01-28

Locations

US (1)