Effects of Ad Libitum Ultra-Processed Diet on Brain Dopamine in Humans

Background:

Dopamine is a chemical that the brain makes when a person expects a reward. Researchers want to learn more about how eating different types of food affects dopamine levels in the brain.

Objective:

To test how eating different foods affects dopamine levels in the brains of healthy people.

Eligibility:

Healthy people aged 18 to 45 years old.

Design:

Participants will be divided into 2 groups (cohorts). Both will have overnight stays in the clinic.

All participants will be screened. They will talk to a dietitian about their eating habits. They will have a test of how much energy their body uses: They will lie on a table with a clear hood over their heads to measure the gases as they breathe.

During the 3 weeks before participants stay at the clinic, a dietitian will call at 3 random times to ask what they ate the day before. They will complete questionnaires. Cohort 1 will wear a device to track their step count for at least 7 days; these participants will be given food to eat for 2 days before they stay in the clinic.

Cohort 1 will stay in the clinic for 14 days. They will eat as much or as little as they would like on 2 different diets for 5 days each and a normal diet on the other days. They will have blood collected multiple times. They will have 2 d ifferent types of imaging scans. For 1 type, they will receive a drug through a vein to show how much dopamine is in their brains.

Cohort 2 will stay in the clinic for 2 days. They will eat only the foods provided. They will have imaging scans before and after drinking a milkshake. For both scans, they will receive a drug through a vein to show how much dopamine is in their brains. They will have blood collected multiple times.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: [11C] raclopride; Other: liquid nutritive stimulus; Other: Tasteless Oral Stimulus Solution; Other: Minimally Processed Diet; Other: Baseline Diet; Other: Ultra Processed Diet

Detailed Description

Study Description:

In this single-site study, we will recruit a cohort of 32 adult volunteers to a randomized crossover diet study to investigate change in dopamine D2 receptor availability (via [11C]raclopride binding potential). During their participation, after a 2-day outpatient stabilization diet, participants will be admitted for a 14-day, 13-night inpatient stay at the NIH Clinical Center. Following 2 days of inpatient stabilization diet, participants will consume two ad libitum test diets with distinct proportions of ultra-processed food for 5 days each in random order separated by 1 day of stabilization diet. We will collect information via Positron Emission Tomography (PET) about dopamine D2 receptor availability under fasting conditions and dopamine response to an oral stimulus solution. Additionally, magnetic resonance spectroscopy and imaging (MRS, MRI) will be used to collect information on changes in brain GABA tone, white matter hyperintensities, brain iron content, and brain activity in response to the two test diets. Further, we will additionally recruit a cohort of 36 adult volunteers for a 2 day/1night stay at the Clinical Center to measure dopamine D2 receptor availability in the extended post ingestive state to determine whether dopamine release may be quantified in this period of the postprandial state.

Objectives:

• Primary Objective: To determine the impact of two 5-day ad libitum test diets differing in proportion of ultra-processed, energy-dense, hyper-palatable foods on fasting striatal [11C]raclopride dopamine D2 receptor binding potential (D2BP) as well as the magnitude of any change from baseline.
• Secondary Objective: To determine differences in spatiotemporal components of striatal dopamine response (rDA) to a milkshake after two 5-day ad libitum test diets matched for presented nutrients but different in proportion of ultra-processed, energy-dense, hyperpalatable foods.
• Secondary Objective: To determine change in whole striatal dopamine D2BP in the extended post-ingestive period, beginning 1.5 - 3 hours following consumption of a UPF milkshake, as measured by [11C]raclopride

Endpoints:

• Primary Endpoint: Dopamine D2 receptor binding potential (D2BP) in the striatum after two test diets will be quantified during steady state portion of 20mCi [11C]raclopride infusion PET neuroimaging.
• Secondary Endpoint: Regionally and temporally specific dopamine response to in-scanner milkshake consumption and digestion after 5 days of each test diet will be determined voxelwise (spatial) over a duration of [11C]raclopride infusion (temporal), compared to equivalent endpoints for "tasteless" oral stimulus.
• Secondary Endpoint: D2BP in the striatum will be quantified using a bolus of 20mCi [11C]raclopride in both the overnight fasted state and delayed post-ingestive state for each participant.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nan Zhai, C.R.N.P.; Phone Number: (301) 827-3324; Email: nan.zhai@nih.gov
• Study Contact Backup: Name: Valerie L Darcey; Phone Number: (301) 402-9689; Email: valerie.darcey@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center
      • Contact: Valerie Darcey; Phone Number: 301-402-9689; Email: valerie.darcey@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• INCLUSION CRITERIA

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

1. Aged 18 to 45 years old

2. In good general health as evidenced by medical history

3. Weight stable (< +/- 5% change in last 6 months), based on self-report

4. BMI

   1. Cohort 1: 18.5 - 24.9 kg/m^2
   2. Cohort 2: >= 18.5 kg/m^2

EXCLUSION CRITERIA

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Body weight > 400 lbs. (weight limit of PET scanner)
2. History or current self-report of conditions that may influence appetite, in the opinion of the study investigators, including but not limited to cancer, diabetes mellitus, evidence of metabolic dysfunction, changes in senses of smell or taste (e.g., covid-related), or metabolic/bariatric surgery
3. History or current neurological, mood, eating, or substance use disorders by self-report, history/physical, Eating Disorder Examination Questionnaire, and/or DSM-5 Cross-cutting symptom measure.
4. Measured resting energy expenditure +/- 30% of that predicted by Mifflin St-Jeor equation.
5. Uncontrolled hypertension, with blood pressure >140/90 mm Hg
6. Pregnancy or lactation
7. Known allergic reactions to components of the PET agent, [C-11] raclopride.
8. Having had previous radiation exposure within the last year for either medical or research purposes (e.g. X-rays, PET scans, etc.) that would exceed research limits. Excessive radiation exposure will be determined at the discretion of the PI and/or study team
9. Inability or unwillingness (e.g. due to claustrophobia) to tolerate lying flat on their back for extended periods of time in PET/MR or MRI scanner or (Cohort 1 only) inability to tolerate swallowing drops of liquid delivered onto tongue while lying down on bed.
10. Having metal implants incompatible with MRI (for example, pacemakers, metallic prostheses such as cochlear implants or heart valves, shrapnel fragments, etc.).
11. Left-handedness, by self-report and confirmation via Edinburgh Handedness Survey
12. Self-report of daily alcohol intake > 3 drinks (males) or > 2 drinks (females)
13. Current nicotine use (e.g. cigarette, vaping) determined by participant report or nicotine dependence confirmed by Fagerstrom Nicotine Dependence (score >= 4)
14. Current use of medications or drugs of abuse which may influence appetite or have central effects, in the opinion of study investigators
15. Caffeine consumption > 300 mg/day (roughly >=3 cups coffee or 2-3 energy drinks)
16. Significant dietary restrictions, based on evaluation by nutrition staff and results of nutrition screener (rating fewer than 75% of foods listed as a 4 or higher score on The Food Enjoyment Questionnaire)
17. Unable or unwilling to provide informed consent
18. Unable or unwilling to adhere to study diet, procedures, schedule, and lifestyle considerations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MPF-UPF; Participants will be randomized to the one of two diet sequences (study arms: UPF-MPF vs MPF-UPF) by NIH dietitians after enrollment, in advance of admission. A total of n=32 participants will be evenly grouped into 16 batches according to date of inpatient admission. Within each batch of 2 participants, participants will be randomly assigned to one of the two diet sequences, ensuring any order effects will be counterbalanced and maintaining balance across diet sequence assignments.	Drug: [11C] raclopride; The drug is intended for use as a radiopharmaceutical for positron emission tomography (PET) administered at a maximum prescribed dose of 20mCi and will be administered intravenously via indwelling catheter; Other: liquid nutritive stimulus; The ~8 oz liquid meal will be high in both dietary fat and sugar and ultra-processed designation based on ingredients and will be prepared by the NIH Clinical Center Metabolic Kitchen for participant consumption during the PET scans at the end of both test dietary intervention periods (Cohort 1) or for consumption between the PET scans (Cohort 2).; Other: Tasteless Oral Stimulus Solution; The control stimulus is a non-rewarding tasteless solution with viscosity distinct from pure water (i.e., artificial saliva). Four dilutions of 25mM potassium chloride + 2.5mM sodium bicarbonate will be prepared by NIH Clinical Center Pharmacy for participant oral stimulus taste test; Other: Minimally Processed Diet; The minimally processed diet will derive ~80% of calories from minimally processed foods and will contain no ultra-processed foods, (NOVA 1-3), as defined by the degree, extent, and purpose of processing according to the NOVA classification system. The minimally processed diet will be matched to the ultra-processed diet for presented macronutrients, sugar, sodium, and fiber. This diet will be low in both non-beverage energy density and hyper-palatable foods; Other: Baseline Diet; The baseline (control) diet will be composed of 50% of energy from ultra-processed foods while matching distribution of macronutrients presented in test diets and total sugar, sodium, and fiber). Energy needs will be estimated using resting energy expenditure multiplied by an appropriate activity factor collected at screening visit to facilitate production by the NIH Metabolic Kitchen.
Experimental: UPF-MPF; Participants will be randomized to the one of two diet sequences (study arms: UPF-MPF vs MPF-UPF) by NIH dietitians after enrollment, in advance of admission. A total of n=32 participants will be evenly grouped into 16 batches according to date of inpatient admission. Within each batch of 2 participants, participants will be randomly assigned to one of the two diet sequences, ensuring any order effects will be counterbalanced and maintaining balance across diet sequence assignments.	Drug: [11C] raclopride; The drug is intended for use as a radiopharmaceutical for positron emission tomography (PET) administered at a maximum prescribed dose of 20mCi and will be administered intravenously via indwelling catheter; Other: liquid nutritive stimulus; The ~8 oz liquid meal will be high in both dietary fat and sugar and ultra-processed designation based on ingredients and will be prepared by the NIH Clinical Center Metabolic Kitchen for participant consumption during the PET scans at the end of both test dietary intervention periods (Cohort 1) or for consumption between the PET scans (Cohort 2).; Other: Tasteless Oral Stimulus Solution; The control stimulus is a non-rewarding tasteless solution with viscosity distinct from pure water (i.e., artificial saliva). Four dilutions of 25mM potassium chloride + 2.5mM sodium bicarbonate will be prepared by NIH Clinical Center Pharmacy for participant oral stimulus taste test; Other: Baseline Diet; The baseline (control) diet will be composed of 50% of energy from ultra-processed foods while matching distribution of macronutrients presented in test diets and total sugar, sodium, and fiber). Energy needs will be estimated using resting energy expenditure multiplied by an appropriate activity factor collected at screening visit to facilitate production by the NIH Metabolic Kitchen.; Other: Ultra Processed Diet; The ultra-processed diet will derive ~80% of energy from ultra-processed foods (NOVA 4), as defined by the degree, extent, and purpose of processing according to the NOVA classification system. The ultra processed diet will be matched to the minimally processed diet for presented macronutrients, sugar, sodium, and fiber. This diet will be high in both non-beverage energy density and hyper-palatable foods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dopamine D2 receptor binding potential (D2BP) during steady portion of [11C]raclopride infusion PET neuroimaging	Fasting (steady state) whole striatal dopamine D2 receptor binding at the conclusion of three diet periods (on 4th day of control diet, after 5 full days ad libitum UPF, and after 5 full days ad libitum MPF)	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The magnitude of striatal dopamine responses to orosensory and post-ingestive milkshake exposure	Measured at the conclusion of three diet periods (on 4th day of control diet, after 5 full days ad libitum UPF, and after 5 full days ad libitum MPF).	5 days
The difference between striatal dopamine D2 receptor binding potential	Measured while fasting and 1.3 -3 hours after a palatable liquid meal (Cohort 2).	90-180 minutes

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Valerie L Darcey, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

Helpful Links

• <p>NIH Clinical Center Detailed Web Page</p>

Study record dates

Study Major Dates

• Study Start (Estimated): November 11, 2026
• Primary Completion (Estimated): November 10, 2030
• Study Completion (Estimated): November 10, 2030

Study Registration Dates

• First Submitted: November 5, 2026
• First Submitted That Met QC Criteria: November 5, 2026
• First Posted (Actual): November 6, 2026

Study Record Updates

• Last Update Posted (Actual): November 6, 2026
• Last Update Submitted That Met QC Criteria: November 5, 2026
• Last Verified: October 27, 2026

More Information

Terms related to this study

• Keywords: Neuroimaging; Dopamine Response; Raclopride; Ultra-Processed Foods
• Additional Relevant MeSH Terms: Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Amides; Benzene Derivatives; Acids, Carbocyclic; Benzoates; Benzamides; Chlorobenzoates; Raclopride
• Other Study ID Numbers: 10002388; 002388-DK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data published in Harvard Dataverse (https://dataverse.harvard.edu/) will be accessible to the research community for the long-term. Terms of access to data to require requestors to log in and provide information including their identity and intended use to initiate an access request to Dr. Darcey, the PI.

IPD Sharing Time Frame

Data will be made available as soon as possible or at the time of associated publication, whichever comes first

IPD Sharing Access Criteria

Terms of access to data to require requestors to log in and provide information including their identity and intended use to initiate an access request to Dr. Darcey, the PI.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No