Role of Ultra-processed Foods in Modulating the Effect of Mediterranean Diet (PROMENADE)

Role of ultraPROcessed Foods in Modulating the Effect of mEditerraNeAn Diet on Human and Planet hEalth - the PROMENADE Study

Mediterranean diet is worldwide promoted as one of the healthiest and most sustainable dietary patterns. One of the main pillars of Mediterranean diet is the abundant consumption of plant-based ingredients typically consumed as raw or minimally processed. However, even in the Mediterranean countries, these fresh foods are increasingly replaced by ultra-processed foods (UPF). Epidemiological evidence suggests that consumption of UPF may be detrimental to human health, but there is only one clinical trial on this topic which is largely debated in the scientific community due to limitations related to the short duration of the trial and the composition of dietary interventions.

The present study aims at exploring whether the inclusion of UPF within a Mediterranean-based dietary pattern can impact on cardiometabolic markers, gut microbiota and other health markers in a dietary intervention performed in Italian subjects. For this purpose, 50 clinically healthy subjects will be recruited for a 7-month randomized, open, cross-over dietary trial. Eligible participants will be randomly assigned to consume a 3-month Mediterranean diet high in UPF (intervention group) or a low-UPF Mediterranean diet (control group), spaced by a 1-month wash-out period. The two diets will have the same composition in terms of food groups. However, in the high-UPF Mediterranean diet group, 5 servings/day of UPF, as defined by the NOVA system, will be consumed (e.g., flavored yogurt, breakfast cereals with added sugar, processed meat). In the control group, these foods will be replaced by products from the same food group, but not UPF (e.g., plain yogurt, breakfast cereals with no added sugar, unprocessed meat). The inflammatory potential of pairs of food products, both UPF and non UPF, will be evaluated using an in vitro cell model testing the modulation of inflammatory markers. Before and after each intervention blood, urine and fecal samples will be collected. The primary endpoint is change in low-density lipoprotein (LDL) cholesterol levels from baseline. Among the other markers, blood pressure and anthropometric parameters will be measured; biochemical parameters, adipokines, inflammatory and oxidative stress markers, fecal microbiota composition and short chain fatty acids (SCFAs) will be analyzed. Adherence to the study, dietary intake and food waste production will be evaluated through specific food diaries, useful also for estimating the metabolic food waste.

Study Overview

• Status: Not yet recruiting
• Conditions: Overweight
• Intervention / Treatment: Other: MD high in UPF; Other: MD low in UPF

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daniela Martini; Phone Number: +39 02503 16727; Email: daniela.martini@unimi.it

Study Locations

• Italy
  • Florence, Italy, 54141
    • University of Florence
    • Contact: Monica Dinu; Phone Number: +39 349 3465184; Email: monica.dinu@unifi.it
  • Milan, Italy, 20133
    • University of Milan
    • Contact: Daniela Martini; Phone Number: +39 02503 16727; Email: daniela.martini@unimi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age >18 years
• BMI between 25.0 and 29.9 kg/m2 and the simultaneous presence of at least one of the following criteria, defined by the Guidelines for cardiovascular disease prevention of the European Society of Cardiology:
• total cholesterol levels >190 mg/dL
• LDL-cholesterol levels >115 mg/dL
• triglyceride levels >150 mg/dL
• glucose levels in the range 111-125 mg/dL

Exclusion Criteria:

• presence of current serious illness or unstable condition that requires physician supervision of diet (e.g., recent myocardial infarction, chronic liver disease, inflammatory bowel diseases, renal or digestive disorders)
• pregnancy or intention to become pregnant in the next 12 months
• lactation
• current or recent (past 3 months) use of supplements or antibiotic therapy
• current or recent (past 6 months) adoption of specific restrictive diets (e.g., low-calorie or vegetarian diets)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High UPF; Group starting with the Mediterranean diet (MD) high in ultra-processed foods (UPF)	Other: MD high in UPF; A 3-month dietary intervention with a Mediterranean diet with 5 servings/day of UPF, as defined by the NOVA system (e.g., flavored yogurt, breakfast cereals with added sugar, processed meat).; Other: MD low in UPF; A 3-month dietary intervention with a Mediterranean diet with 5 servings/day of products from the same food group, but non-UPF (e.g., plain yogurt, breakfast cereals with no added sugar, unprocessed meat)
Active Comparator: Low UPF; Group starting with the Mediterranean diet (MD) low in ultra-processed foods (UPF)	Other: MD high in UPF; A 3-month dietary intervention with a Mediterranean diet with 5 servings/day of UPF, as defined by the NOVA system (e.g., flavored yogurt, breakfast cereals with added sugar, processed meat).; Other: MD low in UPF; A 3-month dietary intervention with a Mediterranean diet with 5 servings/day of products from the same food group, but non-UPF (e.g., plain yogurt, breakfast cereals with no added sugar, unprocessed meat)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low-density lipoprotein (LDL) cholesterol levels	Measurement of LDL-cholesterol levels change from the beginning to the end of each of the two intervention phases in mg/dL	7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total cholesterol levels	Measurement of total cholesterol levels change from the beginning to the end of each of the two intervention phases in mg/dL	7 months
High-density lipoprotein (HDL) cholesterol levels	Measurement of HDL cholesterol levels change from the beginning to the end of each of the two intervention phases in mg/dL	7 months
Triglycerides levels	Measurement of triglyceride levels change from the beginning to the end of each of the two intervention phases in mg/dL	7 months
Fasting blood glucose levels	Measurement of fasting blood glucose levels change from the beginning to the end of each of the two intervention phases in mg/dL	7 months
Insulin levels	Measurement of insulin levels change from the beginning to the end of each of the two intervention phases in U/I	7 months
Aspartate aminotransferase (AST) levels	Measurement of AST levels change from the beginning to the end of each of the two intervention phases in U/I	7 months
Alanine aminotransferase (ALT) levels	Measurement of ALT levels change from the beginning to the end of each of the two intervention phases in U/I	7 months
Gamma-glutamyl transferase (GGT) levels	Measurement of GGT levels change from the beginning to the end of each of the two intervention phases in U/I	7 months
Folates levels	Measurement of folate levels change from the beginning to the end of each of the two intervention phases in ng/mL	7 months
Vitamin B12 levels	Measurement of vitamin B12 levels change from the beginning to the end of each of the two intervention phases in pg/mL	7 months
Urea levels	Measurement of urea levels change from the beginning to the end of each of the two intervention phases in mg/dL	7 months
Creatinine levels	Measurement of creatinine levels change from the beginning to the end of each of the two intervention phases in mg/dL	7 months
Body weight	Measurement of body weight change from the beginning to the end of each of the two intervention phases in kg	7 months
Body mass index (BMI)	Measurement of BMI change from the beginning to the end of each of the two intervention phases. Weight and height will be combined to report BMI in kg/m^2	7 months
Fat mass	Measurement of fat mass change from the beginning to the end of each of the two intervention phases. Percentage of fat mass will be assessed using the Akern bioelectrical impedance analyser (model SE 101).	7 months
Concentration of ghrelin in plasma	Measurement of ghrelin change from the beginning to the end of each of the two intervention phases in pg/mL	7 months
Concentration of leptin in plasma	Measurement of leptin change from the beginning to the end of each of the two intervention phases in ng/mL	7 months
Concentration of adiponectin in plasma	Measurement of adiponectin change from the beginning to the end of each of the two intervention phases in microg/mL	7 months
Concentration of resistin in plasma	Measurement of resistin change from the beginning to the end of each of the two intervention phases in ng/mL	7 months
Concentration of visfatin in plasma	Measurement of visfatin change from the beginning to the end of each of the two intervention phases in ng/mL	7 months
Concentration of interleukin (IL)-4 in plasma	Measurement of IL-4 change from the beginning to the end of each of the two intervention phases in pg/mL	7 months
Concentration of interleukin (IL)-6 in plasma	Measurement of IL-6 change from the beginning to the end of each of the two intervention phases in pg/mL	7 months
Concentration of interleukin (IL)-10 in plasma	Measurement of IL-10 change from the beginning to the end of each of the two intervention phases in pg/mL	7 months
Concentration of Protein C-reactive (PCR) in plasma	Measurement of protein C-reactive (PCR) change from the beginning to the end of each of the two intervention phases in mg/L	7 months
Concentration of interferon gamma (IFN-γ) in plasma	Measurement of IFN-γ change from the beginning to the end of each of the two intervention phases in pg/mL	7 months
Concentration of tumor necrosis factor -alpha (TNF-α) in plasma	Measurement of TNF-α change from the beginning to the end of each of the two intervention phases in pg/mL	7 months
DNA damage expressed as number of DNA strand breaks induced by hydrogen peroxide (H2O2)	Measurement of H2O2-induced DNA strand breaks change from the beginning to the end of each of the two intervention phases in percentage (%)	7 months
Concentration of F2-isoprostanes in urine	Measurement of F2-isoprostanes change from the beginning to the end of each of the two intervention phases in pg/mosm	7 months
Gut microbiota composition and function changes	Measurement of gut microbiota composition change from the beginning to the end of each of the two intervention phases. Each subject will be asked for a stool sample at the beginning and at the end of each intervention phases in order to analyse the composition of the gut microbiota and short-chain fatty acids production.	7 months

Collaborators and Investigators

• Sponsor: University of Milan
• Collaborators: University of Florence; University of Teramo

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: March 1, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Mediterranean diet; Sustainability; Food processing; Human health
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Overweight
• Other Study ID Numbers: spe123.23

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No