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

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).

• Anthropometric measure: Weight (kg) [Time frame: Baseline and 4 months]
• Anthropometric measure: Height (m) [Time frame: Baseline and 4 months]
• Anthropometric measure: Waist circumference (cm) [Time frame: Baseline and 4 months]
• Anthropometric measure: Hip circumference (cm) [Time frame: Baseline and 4 months]
• Blood pressure (mmHg) [Time frame: Baseline and 4 months]
• Dietary assessment [Time frame: Baseline and 4 months]
• Physical activity [Time frame: Baseline and 4 months]
• Demographic/lifestyle information [Time frame: Baseline and 4 months]
• Continuous Glucose Monitoring (mmol/L) [Time frame: Baseline and 4 months]
• Plasma metabolome [Time frame: Pre and post run-in phase (6 week run-in) ; baseline and 4 months (main trial)]
• Gut microbiome [Time frame: Baseline and 4 months]
• Inflammatory markers e.g. CRP (mg/L) [Time frame: Baseline and 4 months]