Dissecting the Roles of High-quality Diets and Ultra Processed Foods on Cardiometabolic Health

Ultra-processed Foods, Diet Quality, and Cardiometabolic Health

Controversy remains around the role of ultra-processed food (UPF) consumption and health outcomes. A key question that remains to be answered is: when diet quality is the same, does food processing itself have any independent health effects? The current application aims to isolate the health effects of food processing from those of diet quality through the conduct of a dietary intervention study.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiometabolic Risk Factors
• Intervention / Treatment: Behavioral: High UPF, high hPDI diet; Behavioral: Low UPF, high hPDI diet

Detailed Description

Controversy remains around the role of UPF consumption and health outcomes. A key question that remains to be answered is: When diet quality is the same, does food processing itself have any independent health effects?

The current study aims to isolate the health effects of food processing from those of diet quality through the conduct of a dietary intervention study.

To isolate the health effects of food processing, the investigators propose to use healthy plant-based diets as the "base" diet. The investigators propose to initially discover plasma metabolomic features responsive to improved hPDI adherence and then conduct a dietary intervention trial to evaluate the impact of UPF consumption, in the setting of a high hPDI diet, on cardiometabolic outcomes and metabolic pathways.

The study will consist of a run-in phase where participants with a low adherence to a plant based diet will be randomized into (1) an intervention group that will receive diet counselling to follow a high hPDI diet over a period of 6 weeks and (2) a control group that will consume their usual diet (low hPDI). Both arms will be advised to avoid ultra processed food (UPF) consumption. Assuming 15% attrition, the study will enrol 118 participants for the run-in phase. Individuals with a high adherence to plant based diet will follow their normal diet for the 6 weeks of this run-in phase and then will be randomised into the main 4 month study.

In the main four month study, a randomized controlled parallel group dietary intervention will be conducted in participants with high hPDI in Ireland (North and South) to evaluate the impact of UPF consumption, in the context of a high hPDI diet, on cardiometabolic outcomes such as glycated haemoglobin and total cholesterol, and metabolic pathways. Participants will be randomized into one of 2 groups: high UPF hPDI diet or low UPF hPDI diet. Assuming an attrition rate of 15%, the study will enrol ~212 individuals to achieve a sample size of 180 participants who will complete the trial.

Randomization will be performed using a randomization scheme generated using www.randomization.com with random block sizes by research staff independent of the study. The investigators will stratify randomization according to age and BMI.

Power calculation : Assuming a change in total cholesterol of 9 mg/dL at four months and assuming a SD of change of 20, a total of 78 participants in each group is needed. Allowing for participant dropout of 15%, which is similar to that observed in the investigator's previous interventions, gives an overall sample size of 180.

Based on an SD of difference in change in HbA1c of 0.3%, the same sample size could detect as statistically significant a difference in HBA1c of 0.15% between the two intervention groups at four months.

The total number of participants that will be enrolled will be 330: 118 (run-in phase) and 212 (4 month trial).

• Study Type: Interventional
• Enrollment (Estimated): 330
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Prof. Jayne Woodside, PhD; Phone Number: +4402890 978942; Email: j.woodside@qub.ac.uk

Study Locations

• Ireland
  • Ireland
    • Dublin, Ireland, Ireland, D04 C1P1
      • University College Dublin
      • Contact: Professor Lorraine Brennan, PhD; Phone Number: +353 01 716 6815
• United Kingdom
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT12 6BJ
      • Centre for Public Health, Queen's University Belfast
      • Contact: Jayne Woodside V Professor, PhD; Phone Number: +44(0)2890 978942; Email: j.woodside@qub.ac.uk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Men and women aged between 18 and 65 years in general good health with BMI < 35 kg/m2 who can provide informed consent.

Exclusion Criteria:

• Participants will be ineligible to enrol if they have diabetes, CVD, any type of cancer (except for basal cell skin cancer), or a condition (pregnancy, breastfeeding, etc) or dietary restriction(s) that would substantially limit their ability to complete the study.

Individuals will be screened for their adherence to the Plant based diet Index (PDI ).

1. Individuals with low adherence will enter run-in phase only (6 weeks)
2. Individuals with high adherence will enter the main intervention (4 months)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High UPF, high hPDI diet; High ultra-processed foods (UPFs) and healthy plant based diet	Behavioral: High UPF, high hPDI diet; High ultra-processed foods (UPFs) and healthy plant based diet
Active Comparator: Low UPF, high hPDI diet; Low ultra-processed foods (UPFs) and high healthy plant-based diet	Behavioral: Low UPF, high hPDI diet; Low ultra-processed foods (UPFs) and high healthy plant-based diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycated haemoglobin (HbA1C) (mmol/mol)	Change in HbA1c over the course of the 4 month intervention.	Baseline and 4 months
Total cholesterol (mg/dL)	Change in total cholesterol will be measured over the course of the 4 month intervention.	Baseline and 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anthropometric measure: Weight (kg)	Weight (kg) measured using calibrated scales at baseline and 4 months	Baseline and 4 months
Anthropometric measure: Height (m)	Height (m) measured using stadiometer at baseline and 4 months.	Baseline and 4 months
Anthropometric measure: Waist circumference (cm)	Waist circumference (cm) measured at baseline and 4 months.	Baseline and 4 months
Anthropometric measure: Hip circumference (cm)	Hip circumference (cm) measured at baseline and 4 months.	Baseline and 4 months
Blood pressure (mmHg)	Blood pressure will be measured twice from the right arm, using an automated Omron sphygmomanometer, with the participant sitting quietly for at least five minutes in advance	Baseline and 4 months
Dietary assessment	2x 24-hour dietary recalls	Baseline and 4 months
Demographic/lifestyle information	E.g. alcohol use, medication use.	Baseline and 4 months
Continuous Glucose Monitoring (mmol/L)	Continuous glucose monitoring (mmol/L) at baseline and 4 months	Baseline and 4 months
Plasma metabolome	Fasting blood samples will be drawn from the antecubital vein and immediately separated into plasma.	Pre and post run-in phase (6 week run-in) ; baseline and 4 months (main trial)
Gut microbiome	Stool samples will be collected at home within 24 h of the study visit and brought to the laboratory for storage. Samples will be profiled for gut microbiota composition and functional potentials.	Baseline and 4 months
Inflammatory markers e.g. CRP (mg/L)	Changes in inflammatory markers such as CRP (mg/L) over the course of the 4 month intervention	Baseline and 4 months
Physical activity	Questionnaire/objective physical activity monitor. Higher scores in both questionnaire and physical activity monitor will indicate improved outcome.	Baseline and 4 months

Collaborators and Investigators

• Sponsor: Queen's University, Belfast
• Collaborators: University College Dublin; Harvard School of Public Health (HSPH)
• Investigators: Principal Investigator: Prof. Lorraine Brennan, PhD, University College Dublin

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: December 12, 2024
• First Submitted That Met QC Criteria: December 18, 2024
• First Posted (Actual): December 27, 2024

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Diet quality; Cardiometabolic risk factors; Ultra-processed foods; Plant-based diets
• Other Study ID Numbers: TBC (TBC)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No