Targeting DNA-methylation Fingerprints Linked to Ultra-Processed Foods Consumption to Prevent Non-communicable Diseases: the METHYL-UP Study (METHYL-UP)

Non-communicable diseases (NCD) are the main health challenge in industrialized countries. However, these diseases are preventable if an intervention based on lifestyle is implemented at the population level. Diet has a great impact on the onset and progression of NCD. In this regard, ultra-processed food (UPF) consumption has been related to higher morbidity and mortality. UPF are defined as "formulations made mostly or entirely from substances derived from foods and additives, with little if any intact unprocessed or minimally processed foods" (NOVA definition). UPF are rich in saturated fats and additives and poor in fiber other nutrients. UPF consumption has raised in the last decades in the industrialized countries and this increase has been associated with higher prevalence of metabolic disorders such as diabetes, obesity, metabolic syndrome, cardiovascular disease, and cancer. However, mechanisms that link UPF consumption with NCD are poorly understood and clinical trials are needed to unravel these mechanisms and how to impact on them through lifestyle interventions. The investigators have previously identified DNA methylation marks associated with UPF consumption. DNA methylation marks are modifiable. The aim of the study is to assay if DNA methylation marks related to UPF consumption are reversible by reducing UPF consumption in a population of adults with overweight or obesity and with a high basal UPF consumption (>35% of total food consumption in g/day).

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight
• Intervention / Treatment: Other: Control; Other: Nutritional intervention

Detailed Description

The investigators propose a controlled, randomized, parallel groups intervention study based on nutritional counseling to reduce UPF consumption. Eligible participants are adults (18-50 years old), men and women, with overweight or obesity (BMI 25-40 Kg/m2) with a high basal consumption of UPF (>35% of total intake in g/day).

Recruited participants will be randomly allocated into a control group or an intervention group. Participants in the control group will be provided with nutritional guidelines to follow a healthy diet based on a Mediterranean diet. Participants in the intervention group will follow a nutritional intervention program aimed to reduce UPF consumption. Nutritional intervention will not modify basal caloric intake but will record energy intake along the intervention. Nutritional counseling will be based on nutritional educational material such as encourage and discourage food items, recipes, menus and food shopping lists based on unprocessed or minimally processed foods.

Total intervention will last 6 months for both groups. During the intervention phase, a monthly interview with nutritionist/dietitian is scheduled. Face-to-face interviews will be carried out in months 2 and 4. Phone interviews will be carried out in months 1, 3 and 5. In the baseline and final visits (months 0 and 6) a sample and data collection will be performed.

Data collected will include general socio-demographical data (age, sex, educational level, working status, civil status, rural/urban status), lifestyle data (smoking habits, dietary habits, physical activity, sleeping habits), anthropometric data (height, weight, waist circumference, body composition), and clinic-phenotypical parameters (blood pressure, medication, adverse effects, disease prevalence). Biological sample collection will include blood, urine, saliva and feces. Biochemical and blood cells parameters will be measured (blood cell count, glucose, lipid and hepatic profiles).

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lidia Daimiel Ruiz, PhD; Phone Number: 309 +34 917278100; Email: lidia.daimiel@imdea.org
• Study Contact Backup: Name: Celia Martínez Pérez, PhD; Phone Number: 310 +34 917278100; Email: celia.martinez@imdea.org

Study Locations

• Spain
  • Madrid, Spain, 28049
    • IMDEA Food

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men/women
• 18-50 years old
• BMI 25-40 Kg/m2
• UPF consumption > 35% of total intake in g/day

Exclusion Criteria:

• Pregnancy
• Menopause
• IMC <25 Kg/m2 or > 40 Kg/m2
• Excessive alcohol consumption
• Prevalent cardiovascular, renal, lung, pancreatic or liver disease
• Type 1 diabetes
• Type 2 diabetes with poor glucose control or unstable medication during last 3 months
• Prevalent endocrine disease
• Changes in anti-hypertensive medication during last 3 months
• Insulin, systemic anti-inflammatory, or glucocorticoid medication during last 3 months
• Food allergies or intolerances
• Psychosocial or cultural factors that prevent from following the intervention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Control Group; Participants in the control group will be provided with nutritional guidelines to follow a healthy diet based on a Mediterranean diet.	Other: Control; General counseling to adhere to a healthy Mediterranean diet
EXPERIMENTAL: Intervention group; Participants in the intervention group will follow a nutritional intervention program aimed to reduce UPF consumption. Nutritional intervention will not modify basal caloric intake but will record energy intake along the intervention. Nutritional counseling will be based on nutritional educational material such as encouraged and discouraged food items, recipes, menus and food shopping lists based on unprocessed or minimally processed foods.	Other: Nutritional intervention; A nutritional intervention program aimed to reduce UPF consumption. Nutritional intervention will not modify basal caloric intake but will record energy intake along the intervention. Nutritional counseling will be based on nutritional educational material such as encouraged and discouraged food items, recipes, menus and food shopping lists based on unprocessed or minimally processed foods. Total intervention will last 6 months for both groups. During the intervention phase, a monthly interview with nutritionist/dietitian is scheduled. Face-to-face interviews will be carried out in months 2 and 4. Phone interviews will be carried out in months 1, 3 and 5. In the baseline and final visits (months 0 and 6) a sample and data collection will be performed.; Other Names: Reduction of UPF consumption

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UPF	Ultra-processed food consumption	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	Weight change (Kg)	6 months
BMI	Change in body mass index (Kg/m2)	6 months
Obesity	Percentage of participants who reverse obesity condition (BMI < 30 Kg/m2)	6 months
Body composition	Change in % of fat mass	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA methylation	Reversibility of DNA methylation marks	12 months
Glucose	Change in fastin glucose levels (mg/dL)	9 months
Glycated haemoglobin	Change in fastin glycated haemoglobin levels (%)	9 months
Triglycerides	Change in fasting triglycerides levels (mg/dL)	9 months
LDL-cholesterol	Change in fasting LDL-cholesterol levels (mg/dL)	9 months
HDL-cholesterol	Change in fasting HDL-cholesterol levels (mg/dL)	9 months
Liver profile	Change in HSI liver function index	9 months
Microbiota	Changein microbiota diversity	24 months

Collaborators and Investigators

• Sponsor: IMDEA Food

Publications and helpful links

General Publications

• Martinez-Perez C, Daimiel L, Climent-Mainar C, Martinez-Gonzalez MA, Salas-Salvado J, Corella D, Schroder H, Martinez JA, Alonso-Gomez AM, Warnberg J, Vioque J, Romaguera D, Lopez-Miranda J, Estruch R, Tinahones FJ, Lapetra J, Serra-Majem L, Bueno-Cavanillas A, Tur JA, Sanchez VM, Pinto X, Delgado-Rodriguez M, Matia-Martin P, Vidal J, Vazquez C, Ros E, Basterra J, Babio N, Guillem-Saiz P, Zomeno MD, Abete I, Vaquero-Luna J, Baron-Lopez FJ, Gonzalez-Palacios S, Konieczna J, Garcia-Rios A, Bernal-Lopez MR, Santos-Lozano JM, Bes-Rastrollo M, Khoury N, Saiz C, Perez-Vega KA, Zulet MA, Tojal-Sierra L, Ruiz ZV, Martinez MA, Malcampo M, Ordovas JM, San-Cristobal R. Integrative development of a short screening questionnaire of highly processed food consumption (sQ-HPF). Int J Behav Nutr Phys Act. 2022 Jan 24;19(1):6. doi: 10.1186/s12966-021-01240-6.
• Konieczna J, Morey M, Abete I, Bes-Rastrollo M, Ruiz-Canela M, Vioque J, Gonzalez-Palacios S, Daimiel L, Salas-Salvado J, Fiol M, Martin V, Estruch R, Vidal J, Martinez-Gonzalez MA, Canudas S, Jover AJ, Fernandez-Villa T, Casas R, Olbeyra R, Buil-Cosiales P, Babio N, Schroder H, Martinez JA, Romaguera D; PREDIMED-Plus investigators. Contribution of ultra-processed foods in visceral fat deposition and other adiposity indicators: Prospective analysis nested in the PREDIMED-Plus trial. Clin Nutr. 2021 Jun;40(6):4290-4300. doi: 10.1016/j.clnu.2021.01.019. Epub 2021 Jan 28.
• Martinez-Perez C, San-Cristobal R, Guallar-Castillon P, Martinez-Gonzalez MA, Salas-Salvado J, Corella D, Castaner O, Martinez JA, Alonso-Gomez AM, Warnberg J, Vioque J, Romaguera D, Lopez-Miranda J, Estruch R, Tinahones FJ, Lapetra J, Serra-Majem L, Bueno-Cavanillas A, Tur JA, Sanchez VM, Pinto X, Gaforio JJ, Matia-Martin P, Vidal J, Vazquez C, Ros E, Bes-Rastrollo M, Babio N, Sorli JV, Lassale C, Perez-Sanz B, Vaquero-Luna J, Bazan MJA, Barcelo-Iglesias MC, Konieczna J, Rios AG, Bernal-Lopez MR, Santos-Lozano JM, Toledo E, Becerra-Tomas N, Portoles O, Zomeno MD, Abete I, Moreno-Rodriguez A, Lecea-Juarez O, Nishi SK, Munoz-Martinez J, Ordovas JM, Daimiel L. Use of Different Food Classification Systems to Assess the Association between Ultra-Processed Food Consumption and Cardiometabolic Health in an Elderly Population with Metabolic Syndrome (PREDIMED-Plus Cohort). Nutrients. 2021 Jul 20;13(7):2471. doi: 10.3390/nu13072471.

Helpful Links

• Research team profile
• Research team profile

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 6, 2021
• Primary Completion (ACTUAL): December 31, 2022
• Study Completion (ACTUAL): December 31, 2022

Study Registration Dates

• First Submitted: March 21, 2022
• First Submitted That Met QC Criteria: March 31, 2022
• First Posted (ACTUAL): April 8, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 13, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Obesity; Clinical trial; Precision nutrition; Epigenetics; Methylation; Causal inference; Non-communicable diseases; Ultra-processed food; NOVA
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Body Weight; Overweight; Noncommunicable Diseases
• Other Study ID Numbers: IMD: PI-048

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Informed consent does not allow to make data publicly available. Nevertheless, data could be share upon request to the investigators.

Drug and device information, study documents

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