Metabolomics-Driven Insights Into Ultra-Processed Foods

Metabolomics-Driven Insights Into Ultra-Processed Foods: Identifying High-Risk UPF Subtypes for T2D Prevention

The goal of this dietary intervention study in generally healthy adults is to develop new ways to use blood samples to measure the common types of highly processed foods and beverages that people eat on a regular basis. The main aims to answer are:

What small molecules are elevated in blood after eating different types of highly processed foods and beverages consistently for 1 week?

Researchers will compare 3 different test diets with 1 control diet that does not have any highly processed foods in the same individuals to see which circulating blood markers change.

Participants will:

• Complete 3 diet phases, each 2 weeks long
• Receive a meal plan and study foods and beverages to follow for each 2-week phase
• Come to the clinic every week for blood draws, urine samples, and stool collection kits

Study Overview

• Status: Not yet recruiting
• Conditions: Diet, Food and Nutrition
• Intervention / Treatment: Other: UPF Test Diet A: Starchy, refined grains; Other: UPF Test Diet B: Meat, fish, and bread products; Other: UPF Diet C: Dairy products, including cheese and cream

Detailed Description

UPFs, characterized by industrial processing and the use of cosmetic additives for enhanced palatability and extended shelf-life, account for approximately 58% of caloric intake in the U.S. population. Although some UPF subtypes have been implicated in increasing risk of T2D and other chronic diseases, others may be relatively inert or even beneficial, underscoring the need for discerning their distinct health effects. This trial is a controlled crossover feeding trial design with target enrollment of 40 generally healthy adults. Partcipants complete 3 2-week isocaloric dietary intervention phases, with 1 week of a control diet of non-ultraprocessed foods and beverages, and 1 week of a UPF-based test diet. The 3 UPF test diets each feature a menu consisting of a UPF subtype: starchy and refined grains, meats and fish, or dairy-based products. Foods and beverages are provided during the diet phases, and participants will attend weekly clinic visits for in-person assessments and biospecimen collections. We will obtain metabolomic profiling of the fasting plasma samples and conduct data analyses to isolate novel biomarkers that reflect the intake of the UPFs, such as industrial additives. These objective signatures of UPF intake will support subsequent research investigating the long-term health outcomes relate d to UPF consumption. Identifying metabolomic signatures of UPF subtypes will enhance the understanding of the biological mechanisms linking UPFs to T2D and other chronic disease risks.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Deirdre K Tobias, ScD; Phone Number: 617-278-0844; Email: dtobias@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hopital Center for Clinical Investigation
      • Contact: Yemi Talabi-Oates, MBA; Phone Number: 617-732-8750; Email: cci@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults, ages 20 to 65 years.
• BMI 18.5 to 39.9 kg/m2.
• No known food allergies, intolerances, or sensitivities (e.g., gluten, dairy, monosodium-glutamate).
• Not following a restrictive diet for health, religious, or other reasons (e.g., vegetarian, vegan).
• Willingness to participate and give informed consent.
• Willingness to consume dietary intervention foods and beverages.

Exclusion Criteria:

• BMI <18.5 or >39.9 kg/m2.
• Pregnant, lactating, or planning on becoming pregnant in the next 6 months.
• History of bariatric surgery.
• Currently taking medications impacting appetite or body weight.
• History of major chronic diseases, including cardiovascular disease, type 1 or 2 diabetes, major gastrointestinal conditions, uncontrolled hypertension (seated blood pressure systolic >140 mmHg or diastolic >90 mmHg), history of invasive cancer, current use of immunosuppressants, and other major chronic diseases and conditions affecting participation, adherence, or study endpoints.
• Unwilling or unable to comply with all in person scheduled visits, dietary protocols, study protocol, and other study procedures.
• Food allergies or aversions to the foods provided in the dietary interventions.
• Non-English speaking.
• Other members of the same household are already participating in the research study.
• Planning on moving out of the Boston area in the next 6 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1; Participants receive Diet A, followed by Diet B, followed by Diet C.	Other: UPF Test Diet A: Starchy, refined grains; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consistently of starchy foods and refined grain products. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.; Other: UPF Test Diet B: Meat, fish, and bread products; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consisting of meat, fish, and bread products. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.; Other: UPF Diet C: Dairy products, including cheese and cream; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consisting of dairy products, including cheese and cream. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.
Experimental: Sequence 2; Participants receive Diet A, followed by Diet C, followed by Diet B.	Other: UPF Test Diet A: Starchy, refined grains; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consistently of starchy foods and refined grain products. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.; Other: UPF Test Diet B: Meat, fish, and bread products; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consisting of meat, fish, and bread products. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.; Other: UPF Diet C: Dairy products, including cheese and cream; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consisting of dairy products, including cheese and cream. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.
Experimental: Sequence 3; Participants receive Diet B, followed by Diet A, followed by Diet C.	Other: UPF Test Diet A: Starchy, refined grains; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consistently of starchy foods and refined grain products. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.; Other: UPF Test Diet B: Meat, fish, and bread products; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consisting of meat, fish, and bread products. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.; Other: UPF Diet C: Dairy products, including cheese and cream; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consisting of dairy products, including cheese and cream. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.
Experimental: Sequence 4; Participants receive Diet B, followed by Diet C, followed by Diet A.	Other: UPF Test Diet A: Starchy, refined grains; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consistently of starchy foods and refined grain products. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.; Other: UPF Test Diet B: Meat, fish, and bread products; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consisting of meat, fish, and bread products. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.; Other: UPF Diet C: Dairy products, including cheese and cream; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consisting of dairy products, including cheese and cream. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.
Experimental: Sequence 5; Participants receive Diet C, followed by Diet A, followed by Diet B.	Other: UPF Test Diet A: Starchy, refined grains; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consistently of starchy foods and refined grain products. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.; Other: UPF Test Diet B: Meat, fish, and bread products; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consisting of meat, fish, and bread products. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.; Other: UPF Diet C: Dairy products, including cheese and cream; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consisting of dairy products, including cheese and cream. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.
Experimental: Sequence 6; Participants receive Diet C, followed by Diet B, followed by Diet A.	Other: UPF Test Diet A: Starchy, refined grains; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consistently of starchy foods and refined grain products. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.; Other: UPF Test Diet B: Meat, fish, and bread products; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consisting of meat, fish, and bread products. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.; Other: UPF Diet C: Dairy products, including cheese and cream; The 2-week diet phase includes a standardized control run-in diet with non-UPFs only for 7 days, immediately followed by a 7-day UPF test diet with ~60% of calories from UPFs consisting of dairy products, including cheese and cream. Participants receive all study-provided meals and snacks. The diets are standardized and consumed during the assigned intervention period as part of the randomized crossover feeding trial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Within-person metabolomic response during each UPF test diet, compared to the paired non-UPF control diet.	The primary outcome for this study is within-person metabolomic response during each UPF test diet, compared to the paired non-UPF control diet. Metabolomic responses will be quantified from metabolite concentrations (e.g., relative abundance) measured in fasting plasma samples collected at day 0, day 7, and day 14 in each diet phase.	Day 0, Day 7, and Day 14 of each dietary intervention period

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Broad Institute of MIT and Harvard
• Investigators: Principal Investigator: Deirdre K Tobias, ScD, Brigham and Women's Hospital; Principal Investigator: Shilpa Bhupathiraju, PhD, Brigham and Women's Hospital; Principal Investigator: Frank B Hu, MD PhD, Harvard School of Public Health (HSPH)

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: July 16, 2026
• First Submitted That Met QC Criteria: July 16, 2026
• First Posted (Actual): July 21, 2026

Study Record Updates

• Last Update Posted (Actual): July 21, 2026
• Last Update Submitted That Met QC Criteria: July 16, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: dietary intervention; metabolomics; ultra-processed foods; crossover trial; feeding trial
• Additional Relevant MeSH Terms: Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytological Techniques; Histological Techniques; Genetic Techniques; Histocytological Preparation Techniques; In Situ Hybridization; Staining and Labeling; Cytogenetic Analysis; Nucleic Acid Hybridization; In Situ Hybridization, Fluorescence
• Other Study ID Numbers: 2026P001870; 1R01DK145733-01A1 (Other Grant/Funding Number: NIH (Pending))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: There is a plan to make IPD and related data dictionaries available. We will not share any data that include participant identifiers, sensitive or genomic data, or videos, photographs, or audio recordings.
• IPD Sharing Time Frame: Beginning 1 year after publication with no end date.
• IPD Sharing Access Criteria: A Controlled Access Repository: Requests for data are reviewed by an access committee per established policies and procedures; providers may establish data use restrictions; the access period is limited; a data user's institution must sign a DUA that is similar to an NIH DUC or FDP DTUA template; data users may need to produce a data security plan.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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