An interventional study of No UPF controlled diet and High UPF controlled diet in Cardiovascular Diseases, sponsored by Virginia Polytechnic Institute and State University. Completed at 1 site in United States. Open to participants aged 40 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-01-22.
Sponsored by Virginia Polytechnic Institute and State University · Not applicable, Interventional, and Prevention
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.
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This study's enrollment of 17 is below the median of 100 across 2,738 interventional studies indexed under Cardiovascular Diseases.
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Exclusion Criteria:
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
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
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.
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.
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.
Time frame: 30-minute measurement in the laboratory, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in arterial stiffness (Carotid femoral pulse wave velocity) from baseline to 6-weeks post no or high UPF diet
Carotid femoral (C-F) pulse wave velocity (PWV), the primary measure of arterial stiffness, will be measured. C-F waveforms will be obtained via tonometry (NIHem, Cardiovascular Engineering, Inc). Aortic PWV will be calculated from signal averaged waveforms using the ECG as the fiducial point, and body surface measurements.
Time frame: 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
Stool samples will be collected daily for 3 days before and during the final 3 days of the diet interventions. Samples will be collected daily and placed in sterile plastic containers, stored in personal freezers, and placed in coolers for transport. Upon return to the lab, they will be immediately frozen at -80°C until final processing and analysis.
Time frame: 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
Stool samples will be collected daily for 3 days before and during the final 3 days of the diet interventions. Samples will be collected daily and placed in sterile plastic containers, stored in personal freezers, and placed in coolers for transport. Upon return to the lab, they will be immediately frozen at -80°C until final processing and analysis.
Time frame: 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
Intestinal inflammation will be assessed using fecal calprotectin, lactoferrin, and lipocalin-2, measured using ELISA.
Time frame: 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
Intestinal permeability will be assessed using serum zonulin (Immunodiagnostik AG, Bensheim, Germany) concentrations, measured using ELISA.
Time frame: 3-day collection during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in inflammatory cytokines from baseline to post 6-weeks no or high UPF diet
Inflammatory cytokines, including Tumor Necrosis Factor alpha, Interleukin 6, and Monocyte Chemoattractant Protein-1, will be measured using ELISA (American Diagnostica Inc).
Time frame: 5-minute blood collection in the laboratory, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in endotoxin from baseline to post 6-weeks no or high UPF diet
Serum endotoxin will be assessed using the PyroGene Recombinant Factor C endotoxin assay (Lonza, Basel, Switzerland).
Time frame: 5-minute blood collection in the laboratory, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in insulin sensitivity from baseline to 6-weeks post no or high 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).
Time frame: 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
24-hour glucose control (24-hour mean glucose concentration) will be assessed using continuous glucose monitoring for a 6-day period.
Time frame: 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
24-hour glucose control (24-hour AUC) will be assessed using continuous glucose monitoring for a 6-day period.
Time frame: 6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in 24-hour glucose control (time in range) from baseline to 6-weeks post no or high UPF diet
24-hour glucose control (time in range) will be assessed using continuous glucose monitoring for a 6-day period.
Time frame: 6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in 24-hour glucose control (glycemic variability [GV]) from baseline to 6-weeks post no or high UPF diet
24-hour glucose control (GV) will be assessed using continuous glucose monitoring for a 6-day period.
Time frame: 6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Change in 24-hour glucose control (postprandial glucose) from baseline to 6-weeks post no or high UPF diet
Free-living postprandial glucose concentration will be assessed using continuous glucose monitoring for a 6-day period.
Time frame: 6-day measurement during free-living, 2 timepoints (baseline, 6 weeks post no or high UPF diet)
Plan to share: No
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Virginia Polytechnic Institute and State University