Ultra-processed Food Consumption, Gut Microbiota, and Glucose Homeostasis

NCT05358171 | Completed

• 1 other identifier: 21-974
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Advancing age is associated with gut dysbiosis, low-grade chronic inflammation, progressive insulin resistance, and increased risk of type 2 diabetes (T2D). Prediabetes is present in 45-50% of middle-aged/older adults, and declines in glucose tolerance are evident in the third or fourth decade of life. Thus, there is an urgent need to identify new approaches for the prevention of type 2 diabetes among middle-aged adults. Observational research has linked intake of ultra-processed foods (UPF), which comprise \~60% of total energy intake in US adults, with increased risk of T2D. Ex vivo and animal research suggests that components of UPF alter gut microbiota composition and initiate a cascade of events leading to intestinal inflammation and impaired glycemic control. Whether mid-life adults (aged 45-65 yrs) are susceptible to the adverse impact of UPF consumption on glucose homeostasis is unknown. The overall objective of this study is to establish proof-of-concept for an impairment in glucose homeostasis following increases in UPF consumption in mid-life adults, in order to conduct a larger, more comprehensive and mechanistic trial in the future. In addition, changes in gut microbial composition and function, intestinal inflammation and permeability, serum endotoxin concentrations, and inflammatory cytokines as potential mechanisms by which UPF consumption influences glucose homeostasis will be investigated.

Conditions

Insulin Sensitivity; 24-hour Glucose Control

Outcome Measures

Primary Outcomes (1)

• Change in insulin sensitivity from baseline to 6-weeks post high or no UPF diet

  Insulin sensitivity assessed using a 2-hour oral glucose tolerance test (75g glucose load). Blood will be collected at baseline (fasting), and thereafter at 30-minute intervals (5 total measurements in 2 hours) at baseline and post 6-weeks high or no UPF diet.

  2 timepoints (standardized diet lead-in [baseline]), 6-weeks post high or no UPF diet, 2-hour test in laboratory

Secondary Outcomes (11)

• Change in 24-hour glucose control (24-hour mean) from baseline to 6-weeks post high or no UPF diet

  6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post high or no UPF diet)

• Change in 24-hour glucose control (AUC) from baseline to 6-weeks post high or no UPF diet

  6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post high or no UPF diet)

• Change in 24-hour glucose control (time in range) from baseline to 6-weeks post high or no UPF diet

  6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post high or no UPF diet)

• Change in 24-hour glucose control (glycemic variability [GV]) from baseline to 6-weeks post high or no UPF diet

  6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post high or no UPF diet)

• Change in 24-hour glucose control (postprandial glucose) from baseline to 6-weeks post high or no UPF diet

  6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post high or no UPF diet)

Other Outcomes (3)

• Change in brachial artery function from baseline to 6-weeks post high or no UPF diet

  30-minute measurement in the laboratory, 2 timepoints (baseline, 6 weeks post high or no UPF diet)

• Change in arterial stiffness (Carotid femoral pulse wave velocity) from baseline to 6-weeks post high or no UPF diet

  45-minute measurement in the laboratory, 2 timepoints (baseline, 6 weeks post high or no UPF diet)

• Change in arterial stiffness (Beta-stiffness index) from baseline to 6-weeks post high or no UPF diet

  45-minute measurement in the laboratory, 2 timepoints (baseline, 6 weeks post high or no UPF diet)

Study Arms (2)

HIgh UPF (Ultra-processed foods)

EXPERIMENTAL

Participants will consume a diet containing 81% total energy from UPF for 6 weeks

Other: HIgh UPF controlled diet

No UPF

ACTIVE COMPARATOR

Participants will consume a diet containing 0% total energy from UPF for 6 weeks

Other: No UPF controlled diet

Interventions

HIgh UPF controlled diet OTHER

Following a two- week eucaloric lead-in diet, participants will be provided and consume a diet emphasizing UPF (81% energy). Diets will be eucaloric (50% carbohydrate, 35% fat,15% protein) matched for dietary soluble and insoluble fiber, added sugar, mono- and polyunsaturated fat, saturated fat, antioxidant nutrients, sodium, pre- and probiotics, and overall diet quality, for 6 weeks.

HIgh UPF (Ultra-processed foods)

No UPF controlled diet OTHER

Following a two- week eucaloric lead-in diet, participants will be provided and consume a diet without UPF (0% energy). Diets will be eucaloric (50% carbohydrate, 35% fat,15% protein) matched for dietary soluble and insoluble fiber, added sugar, mono- and polyunsaturated fat, saturated fat, antioxidant nutrients, sodium, pre- and probiotics, and overall diet quality, for 6 weeks.

No UPF

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Weight stable for previous 6 months
• Sedentary to recreationally active
• No plans to gain/lose weight or change physical activity level
• Willing to pick up food daily and consume foods provided for an 8-week period
• Verbal and written informed consent
• Approval by Medical Director
• Estrogen or testosterone usage is acceptable, if on stable dose for \>6 months

You may not qualify if:

• BMI \>35 kg/m2
• Diabetes or diabetes medication
• Antibiotic, prebiotic or prebiotic use in prior 3 months
• TCHOL \>6.2 mmol/L; TG \>4.5 mmol/L
• Blood pressure (BP) \> 159/99 mmHg (Stable BP on antihypertensive medications used for \>6 months is acceptable)
• Diagnosed inflammatory bowel disease
• Past or current heart diseases, stroke, respiratory disease, endocrine or metabolic disease, or hematological-oncological disease
• Vegetarian or vegan
• Pregnant or plans to become pregnant
• Food allergies or aversions
• or fewer stools per week or regular laxative use

Sponsors & Collaborators

• Virginia Polytechnic Institute and State University: lead
• Duke University: collaborator

Study Sites (1)

Virginia Tech

Blacksburg, Virginia, 24061, United States

Location

Related Publications (1)

• Capra BT, Hudson S, Helder M, Laskaridou E, Johnson AL, Gilmore C, Marinik E, Hedrick VE, Savla J, David LA, Davy KP, Davy BM. Ultra-processed food intake, gut microbiome, and glucose homeostasis in mid-life adults: Background, design, and methods of a controlled feeding trial. Contemp Clin Trials. 2024 Feb;137:107427. doi: 10.1016/j.cct.2024.107427. Epub 2024 Jan 4.

  PMID: 38184104 BACKGROUND

MeSH Terms

Conditions

Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Brenda Davy, PhD RDN

  Virginia Polytechnic Institute and State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 22, 2022
• First Posted: May 3, 2022
• Study Start: March 15, 2023
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: January 14, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)