Highly Processed Foods and Vascular Health

NCT05628350 | Completed

• 1 other identifier: 22-819
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Age is the primary risk factor for cardiovascular disease (CVD) and age-related vascular dysfunction is considered the key process linking the two. Middle age is a particularly vulnerable period when risk factors exceed diagnostic thresholds and clinical expression of CVD first becomes evident. Ultra-processed foods (UPF) comprise almost 60% of total energy in the standard American diet. The results of observational studies suggest that UPF consumption increases CVD risk, independent of overall diet quality (i.e., saturated fat, sodium, sugar, and dietary fiber intake). The "industrialized microbiota" may link diet, particularly UPF, to increased inflammation and CVD in middle-aged adults. High intake of UPF increases the likelihood of an excess heart age \>10 years and doubles the risk of subclinical coronary atherosclerosis in middle-aged adults. However, the impact of reducing UPF consumption on vascular function in middle-aged adults is unknown. The overall objective of this study is to establish proof-of-concept for an improvement in vascular function following reductions 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 vascular function will be investigated.

Conditions

Cardiovascular Diseases

Keywords

Middle age; Diet composition; Vascular function

Outcome Measures

Primary Outcomes (1)

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

  Flow Mediated Dilation (FMD) of the brachial artery will be assessed using duplex ultrasonography (GE Logiq e) with a high-resolution linear array transducer. Reactive hyperemia will be produced by inflation of a pediatric BP cuff around the forearm for 5 minutes. Offline analysis of baseline and post-reactive hyperemic diameters and velocities will be performed using edge detection software (Vascular Analysis Tools, Medical Imaging Applications, Inc). Endothelium independent vasodilation (EID) will be assessed by measuring brachial arterial dilation for 10 minutes following administration of 0.4 mg of sublingual nitroglycerine. Both FMD and EID will be expressed as mm and % change from baseline diameter.

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

Secondary Outcomes (7)

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

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

• Change in gut microbial composition from baseline to post 6-weeks no or high UPF diet

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

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

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

• Change in intestinal inflammation from baseline to post 6-weeks no or high UPF diet

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

• Change in intestinal permeability from baseline to post 6-weeks no or high UPF diet

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

Other Outcomes (6)

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

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

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

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

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

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

Study Arms (2)

No UPF (Ultra-processed foods)

EXPERIMENTAL

Following a 2-week eucaloric lead-in diet, participants will be provided and consume a diet without UPF (0% total energy) for 6 weeks.

Other: No UPF controlled diet

High UPF

EXPERIMENTAL

Following a 2-week eucaloric lead-in diet, participants will be provided and consume a diet composed of 81% UPF for 6 weeks.

Other: High 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 with high UPF intake (81% total energy) for 6 weeks. Diets will be eucaloric (50% carbohydrate, 35% fat, 15% protein) and 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.

High UPF

No UPF controlled diet OTHER

Following a two-week eucaloric lead-in diet, participants will be provided and consume a diet without UPF (0% total energy) for 6 weeks. Diets will be eucaloric (50% carbohydrate, 35% fat, 15% protein) and 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.

No UPF (Ultra-processed foods)

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 (\<2 kg change)
• 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
• Usual UPF intake +/-15% of US average of 60% total energy
• Estrogen or testosterone usage is acceptable, if on stable dose for \>6 months
• Lipid-lowering medication usage is acceptable, if on a 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
• Total Cholesterol \>6.2 mmol/L; Triglycerides \>4.5 mmol/L
• Blood pressure (BP) \> 159/99 mmHg (Stable BP on antihypertensive medications 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
• Lipid-lowering medication usage \<6 months

Sponsors & Collaborators

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

Study Sites (1)

Virginia Polytechnic and State University

Blacksburg, Virginia, 24061, United States

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Study Officials

• Kevin Davy, PhD

  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: November 16, 2022
• First Posted: November 28, 2022
• Study Start: July 19, 2023
• Primary Completion: December 18, 2024
• Study Completion: September 30, 2025
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)