Effect of an energy-restricted Mediterranean diet, physical activity and behavioral intervention on the primary prevention of cardiovascular disease

ISRCTN ISRCTN89898870
DOI https://doi.org/10.1186/ISRCTN89898870
Secondary identifying numbers ERC 340918 & FIS PI13/00462
Submission date
28/05/2014
Registration date
24/07/2014
Last edited
23/04/2025
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English Summary

Background and study aims
Predimed-plus is a study that will measure how successful an intensive weight-loss lifestyle intervention involving an energy-restricted (calorie controlled) Mediterranean diet (Mediet), promotion of physical activity and behavioral support (intervention group) is compared to a less intensive intervention (control group) also involving a Mediterranean diet but no energy restrictions and no lifestyle or physical activity programmes. The aim is to see whether the more intensive intervention is more likely to result in long-term weight-loss, a reduced risk of developing cardiovascular disease and a greater quality of life for older people with metabolic syndrome (the medical term for the combination of diabetes, high blood pressure and obesity) than when adopting the Mediterranean diet alone.

Who can participate?
Men aged 55 to 75 years and women aged 60-75 years with a body mass index (BMI) ≥27 to <40 kg/m2, no cardiovascular disease and with metabolic syndrome.

What does the study involve?
Participants are randomly allocated into one of two groups. The low-intensity intervention group are given a non-energy restricted Mediet. The intensive intervention group are given an energy-restricted Mediet, physical activity and behavioral support and weight loss goals. Changes in body weight or any event of cardiovascular disease is recorded once a year, as well as other variables of lifestyle, educational achievement, history of illnesses, medication use, physical activity, dietary habits, and electrocardiography, blood pressure, and anthropometric measurements, neuropsychological and quality of life evaluations, and collection of fasting blood samples and morning spot urine.

What are the possible benefits and risks of participating?
Not provided at registration

Where is the study run from?
Human Nutrition Unit, University Hospital of Sant Joan de Reus, Department of Biochemistry and Biotechnology, Pere Virgili Institute for Health Research, Rovira i Virgili University, Reus, Spain (IP: Jordi Salas-Salvadó); Department of Preventive Medicine and Public Health, University of Navarra-Navarra Institute for Health Research (IdiSNA), Pamplona, Spain (IP: Miguel Ángel Martínez-González); Department of Preventive Medicine, University of Valencia, University Jaume I, Conselleria de Sanitat de la Generalitat Valenciana, Valencia, Spain (IP: Dolores Corella); Cardiovascular Risk and Nutrition Research Group, Servicio de Endocrinología, IMIM (Hospital del Mar Medical Research Institute), Barcelona. Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain (IP: Montse Fitó); Nutritional Epidemiology Unit, Miguel Hernandez University, ISABIAL-FISABIO, Alicante, Spain (IP: Jesús Vioque); Hospital Son Espases (HUSE) and Institute for Health Research Illes Balears (IdISBa), Palma de Mallorca, Spain (IP: Dora Romaguera); Department of Nutrition, Food Sciences, and Physiology, Center for Nutrition Research, University of Navarra, Pamplona, Spain (IP: J.Alfredo Martínez); Department School of Nursing, School of Health Sciences, University of Málaga-IBIMA, Málaga, Spain (IP: Julia Wärnberg); Lipids and Atherosclerosis Unit, Department of Internal Medicine, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain (IP: Jose lopez-Miranda); Department of Internal Medicine, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Barcelona, Spain (IP: Ramon Estruch); Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain (IP: Aurora Bueno-Cavanillas); OSI ARABA, University Hospital Araba, Vitoria, Spain (IP: Fernando Arós); Research Group on Community Nutrition & Oxidative Stress, University of Balearic Islands, Palma de Mallorca, Spain (IP: J.Antonio Tur); Virgen de la Victoria Hospital, University of Málaga, Málaga, Spain (IP: Francisco J. Tinahones); University of Las Palmas de Gran Canaria, Las Palmas, Spain (IP: Lluis Serra-Majem); Biomedicine Institute (IBIOMED); University of León, and Primary Health Care Management of León (Sacyl), León, Spain (IP: Vicente Martín);Department of Family Medicine, Research Unit, Distrito Sanitario Atención Primaria Sevilla, Sevilla, Spain (IP: José Lapetra); Department of Endocrinology, Foundation Jiménez-Díaz, Madrid, Spain (IP: Clotilde Vázquez); Lipids and Vascular Risk Unit, Internal Medicine, University Hospital of Bellvitge, Hospitalet de Llobregat, Barcelona, Spain (IP: Xavier Pintó); Department of Endocrinology, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain (IP: Josep Vidal); Nutritional Genomics and Epigenomics Group, Institute IMDEA-Food, CEI UAM+CSIC, Madrid, Spain (IP: Lidia Damiel); Division of Preventive Medicine, University of Jaén, Jaén, Spain (IP: Miguel Delgado-Rodríguez); Department of Endocrinology and Nutrition, Institute for Health Research Hospital Clínico San Carlos (IdISSC), Madrid, Spain (IP: Pilar Matias).

When is the study starting and how long is it expected to run for?
September 2013 to December 2024

Who is funding the study?
Instituto de Salud Carlos III (several grants, Coordinator, jordi.salas@urv.cat), and the European Research Council (Advanced Research Grant to Miguel A. Martínez-Gonzlaéz, mamartinez#unav.es)

Who is the main contact?
1. Dr Jordi Salas-Salvadó
jordi.salas@urv.cat
2. Miguel A. Martínez-Gonzáléz
mamartinez@unav.es

Study website

Contact information

Dr Jordi Salas-Salvadó
Scientific

Human Nutrition Unit Universitat Rovira i Virgili. C/ Sant Llorenç 21/ Dpto Medicina Preventiva y Salud Pública / Universidad de Navarra. Irunlarrea 1 / Internal Medicine Department Hospital Clinic of Barcelona. Villarroel
170
jordi.salas@urv.cat/ mamartinez@unav.es / restruch@clinic.ub.es
Reus (Tarragona) / Pamplona / Barcelona
43201 / 31008 / 08036
Spain

ORCiD logoORCID ID 0000-0003-2700-7459
Phone +34 (0)977759313
Email jordi.salas@urv.cat

Study information

Study designRandomized controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Other
Study typePrevention
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleCardiovascular effect of an intensive weight-loss lifestyle intervention based on an energy-restricted traditional Mediterranean diet (Mediet) together promotion of physical activity and behavioral support in comparison with a less intensive program using Mediet, but without energy restriction or other lifestyle changes: a randomized field trial
Study acronymPREDIMED-Plus
Study hypothesisAn intensive lifestyle intervention with an energy-restricted Mediet, promotion of physical activity, and behavioral support in comparison with Mediet alone, without other lifestyle changes, will reduce the risk of major cardiovascular outcomes (myocardial infarction, stroke, and cardiovascular mortality), be effective for weight loss and long-term weight-loss maintenance, and improve quality of life in older individuals with metabolic syndrome.
Ethics approval(s)Institutional Review Board of all participating centers
ConditionCardiovascular disease
InterventionParticipants are randomly assigned into two equal groups:
1. Low-intensity intervention with a 14-item Mediet (with supplemental extra-virgin olive oil and tree nuts given at no cost for the participant) without energy-restriction, without weight loss goals and without a physical activity program.
2. Intensive intervention with an energy-restricted Mediet (with supplemental extra-virgin olive oil and tree nuts given at no cost for the participant) together with promotion of physical activity, behavioral support and weight loss goals.

All participants will follow a 4-week run-in period to ensure compliance with the protocol. If compliant, they will be randomly allocated to one of the 2 interventions.

Added 04/06/2018:
Each recruiting center randomly assigned candidates in a 1:1 ratio to either the intervention or the control group. Randomisation was performed using a centrally controlled, computer-generated random-number internet-based system with stratification by center, sex, and age categories (<65, 65-70, >70-years) and using blocks of 6 participants. Couples living in the same household who both met eligibility criteria were randomized together as clusters. Consequently the second member of each household was not individually randomised. In the specific cases of couples in which the spouse was recruited at different times, the last spouse entering the study was assigned (not randomised) to the same study arm than his/her partner.
Intervention typeOther
Primary outcome measureCurrent primary outcome measures as of 04/06/2018:
1. A composite endpoint of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke
2. Changes in body weight
All participants are evaluated yearly for primary and secondary endpoints

Previous primary outcome measures:
1. A composite endpoint of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke
2. Changes of body weight
3. Changes in quality of life
All participants are evaluated yearly for primary and secondary endpoints
Secondary outcome measuresCurrent secondary outcome measures as of 15/07/2019:
Death of any cause, changes in waist circumference, and incidence of acute coronary syndrome (unstable angina), coronary revascularization (percutaneous or surgical), atrial fibrillation, peripheral artery disease, heart failure, venous thrombosis, type 2 diabetes mellitus and its complications, dementia, Parkinson disease, major unipolar depression, osteoporotic fractures, cholelithiasis or cholecystectomy, symptomatic gout, transient ischemic attack, cataract, venous thromboembolism or cancer (breast, prostate, lung, colorectal, or stomach) and serum metabolome changes.

Other intermediate outcomes are changes in:
1. Blood pressure
2. Fasting blood sugar
3. Serum lipid profile
4. Markers of inflammation
5. Other intermediate markers of cardiovascular risk
6. Overall diet and nutrient intake
7. Medication use
8. ECGs
9. Cognitive function, quality of life, and psychological and neuropsychological scores
10. Microbiome
11. Epigenetic tags (methylation, miRNA, lncRNA)
12. Genetic polymorphisms
13. Gene expression
13. Taste and odor perception tests

All participants are evaluated yearly for primary and secondary endpoints

Previous secondary outcome measures as of 06/02/2019:
Death of any cause, changes in waist circumference, and incidence of acute coronary syndrome (unstable angina), coronary revascularization (percutaneous or surgical), atrial fibrillation, peripheral artery disease, heart failure, venous thrombosis, type 2 diabetes mellitus and its complications, dementia, Parkinson disease, major unipolar depression, osteoporotic fractures, cholelithiasis or cholecystectomy, symptomatic gout, transient ischemic attack, cataract, venous thromboembolism or cancer (breast, prostate, lung, colorectal, or stomach).

Other intermediate outcomes are changes in:
1. Blood pressure
2. Fasting blood sugar
3. Serum lipid profile
4. Markers of inflammation
5. Other intermediate markers of cardiovascular risk
6. Overall diet and nutrient intake
7. Medication use
8. ECGs
9. Cognitive function, quality of life, and psychological and neuropsychological scores
10. Microbiome
11. Epigenetic tags (methylation, miRNA, lncRNA)
12. Genetic polymorphisms
13. Gene expression
13. Taste and odor perception tests

All participants are evaluated yearly for primary and secondary endpoints

Previous secondary outcome measures as of 04/06/2018:
Death of any cause, changes in waist circumference, and incidence of acute coronary syndrome (unstable angina), coronary revascularization (percutaneous or surgical), atrial fibrillation, peripheral artery disease, heart failure, type 2 diabetes mellitus and its complications, dementia, Parkinson disease, major unipolar depression, osteoporotic fractures, cholelithiasis or cholecystectomy, symptomatic gout, transient ischemic attack, cataract, venous thromboembolism or cancer (breast, prostate, lung, colorectal, or stomach).

Other intermediate outcomes are changes in:
1. Blood pressure
2. Fasting blood sugar
3. Serum lipid profile
4. Markers of inflammation
5. Other intermediate markers of cardiovascular risk
6. Overall diet and nutrient intake
7. Medication use
8. ECGs
9. Cognitive function, quality of life, and psychological and neuropsychological scores

All participants are evaluated yearly for primary and secondary endpoints

Previous secondary outcome measures:
Death of any cause and incidence of angina leading to a revascularization procedure, atrial fibrillation, peripheral artery disease, heart failure, diabetes mellitus and its complications, dementia, Parkinson disease, major unipolar depression, osteoporotic fractures, cholelithiasis or cholecystectomy, symptomatic gout or cancer (breast, prostate, lung, colorectal, or stomach).

Other intermediate outcomes are changes in:
1. Blood pressure
2. Fasting blood sugar
3. Serum lipid profile
4. Markers of inflammation
5. Other intermediate markers of cardiovascular risk
6. Overall diet and nutrient intake

All participants are evaluated yearly for primary and secondary endpoints
Overall study start date05/09/2013
Overall study end date22/12/2024

Eligibility

Participant type(s)Patient
Age groupSenior
Lower age limit55 Years
Upper age limit75 Years
SexBoth
Target number of participants6000
Total final enrolment6874
Participant inclusion criteria1. Participants are community-dwelling high-risk people.
2. Men aged 55 to 75 years and women aged 60 to 75 years
3. Body mass index (BMI) between ≥ 27 y < 40 kg/m2
4. No cardiovascular disease (CVD) at enrolment
5. Who fulfil at least 3 of the criteria for the metabolic syndrome (Alberti et al., 2009). Diabetic participants will represent not more than 25% of the final sample.
Participant exclusion criteriaCurrent exclusion criteria as of 04/06/2018:
1. Illiteracy or inability/unwillingness to give written informed consent or communicate with study staff
2. Institutionalization (the participant is a permanent or long-stay resident in a nursing home)
3. Documented history of previous CVD, including angina; myocardial infarction; coronary revascularization procedures; stroke (either ischemic or haemorrhagic, including transient ischemic attacks); symptomatic peripheral artery disease; ventricular arrhythmia; uncontrolled atrial fibrillation; congestive heart failure (new york heart association class II or IV); hypertrophic cardiomyopathy; or history of aortic aneurysm
4. Active malignant cancer or history of malignancy within the last 5 years (with exception of non-melanoma skin cancer)
5. Impossibility to follow the recommended diet (for religious reasons, swallowing disorders, or other reasons) or to perform physical activity
6. A low predicted likelihood to change dietary habits according to the Prochaska and Diclemente stages of change model (Nigg et al., 1999)
7. Inability to follow the scheduled intervention visits (institutionalized individuals, lack of autonomy, unable to walk, lack of a stable address, travel plans, or other reason that render the subject unable to attend scheduled visits)
8. Body weight loss > 5 kg during the 6 months prior to the screening visit
9. Intention to undergo bariatric surgery in the next 6 months
10. History of very low-caloric diet during the 6 months prior to the screening visit
11. Prior bariatric surgery or indication and willingness to receive a surgical procedure for weight loss in the near future
12. History of inflammatory bowel disease or small bowel resection
13. Obesity of known endocrine origin (with the exception of treated hypothyroidism)
14. Food allergy to any Mediet component
15. Immunodeficiency or HIV-positive status
16. Liver cirrhosis or chronic renal failure
17. Serious psychiatric disorders: schizophrenia, bipolar disease, eating disorders, depression with hospitalization in past 6 months
18. Any severe co-morbid condition with less than 24-month life expectancy
19. Alcohol abuse or addition (total daily alcohol intake >50 g) or drug abuse within the past 6 months
20. History of major organ transplantation
21. Concurrent therapy with immunosuppressive drugs or cytotoxic agents
22. Current treatment with systemic corticosteroids
23. Current use of weight loss medication
24. Concurrent participation in another randomised clinical trial
25. Patients with an acute infection or inflammation (i.e., pneumonia) are allowed to participate in the study 3 months after resolution of their condition
26. Any other condition that may interfere with the completion of the study protocol

Previous exclusion criteria:
1. Unable or unwilling to give written informed consent or communicate with study staff
2. Documented history of previous CVD, including angina; myocardial infarction; coronary revascularization procedures; stroke (either ischemic or haemorrhagic, including transient ischemic attacks); symptomatic peripheral artery disease; ventricular arrhythmia; uncontrolled atrial fibrillation; congestive heart failure (new york heart association class II or IV); hypertrophic cardiomyopathy; or history of aortic aneurysm
3. Active malignant cancer or history of malignancy within the last 5 years (with exception of non-melanoma skin cancer)
4. Impossibility to follow the recommended diet (for religious reasons, swallowing disorders, or other reasons)
5. A low predicted likelihood to change dietary habits according to the Prochaska and Diclemente stages of change model (Nigg et al., 1999)
6. Inability to follow the scheduled intervention visits (institutionalized individuals, lack of autonomy, unable to walk, lack of a stable address, travel plans, or other reason that render the subject unable to attend scheduled visits)
7. Body weight loss > 5 kg during the 6 months prior to the screening visit
8. Intention to undergo bariatric surgery in the next 6 months
9. History of very low-caloric diet during the 6 months prior to the screening visit
10. Prior bariatric surgery or indication and willingness to receive a surgical procedure for weight loss in the near future
11. History of inflammatory bowel disease or small bowel resection
12. Obesity of known endocrine origin (with the exception of treated hypothyroidism)
13. Food allergy to any Mediet component
14. Immunodeficiency or HIV-positive status
15. Liver cirrhosis or chronic renal failure
16. Psychiatric disorders: schizophrenia, bipolar disease, eating disorders, depression with hospitalization in past 6 months
17. Any severe comorbid condition with less than 24-month life expectancy
18. Alcohol (total daily alcohol intake >50 g) or drug abuse within the past 6 months
19. History of major organ transplantation
20. Illiteracy
21. Concurrent therapy with immunosuppressive drugs or cytotoxic agents
22. Current treatment with systemic corticosteroids
23. Current use of weight loss medication
24. Concurrent participation in another randomised clinical trial
25. Patients with an acute infection or inflammation (i.e., pneumonia) are allowed to participate in the study 3 months after resolution of their condition
26. Any other condition that may interfere with the completion of the study protocol
Recruitment start date05/09/2013
Recruitment end date05/12/2016

Locations

Countries of recruitment

  • Spain

Study participating centres

Human Nutrition Unit
University Hospital of Sant Joan de Reus
Department of Biochemistry and Biotechnology
Pere Virgili Institute for Health Research
Rovira i Virgili University
Reus
-
Spain
Department of Preventive Medicine and Public Health
University of Navarra-Navarra Institute for Health Research (IdiSNA)
Pamplona
-
Spain
Department of Preventive Medicine
University of Valencia
University Jaume I
Conselleria de Sanitat de la Generalitat Valenciana
Valencia
-
Spain
Cardiovascular Risk and Nutrition Research Group
Servicio de Endocrinología, IMIM (Hospital del Mar Medical Research Institute)
Barcelona
-
Spain
Departament de Medicina
Universitat Autònoma de Barcelona
Barcelona
-
Spain
Nutritional Epidemiology Unit
Miguel Hernandez University
ISABIAL-FISABIO
Alicante
-
Spain
Hospital Son Espases (HUSE) and Institute for Health Research Illes Balears (IdISBa)
Palma de Mallorca
-
Spain
Department of Nutrition, Food Sciences, and Physiology
Center for Nutrition Research
University of Navarra
Pamplona
-
Spain
Department School of Nursing
School of Health Sciences
University of Málaga-IBIMA
Málaga
-
Spain
Lipids and Atherosclerosis Unit
Department of Internal Medicine
Maimonides Biomedical Research Institute of Cordoba (IMIBIC)
Reina Sofia University Hospital
University of Cordoba
Cordoba
-
Spain
Department of Internal Medicine
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Hospital Clínic
University of Barcelona
Barcelona
-
Spain
Department of Preventive Medicine and Public Health
University of Granada
Granada
-
Spain
OSI ARABA, University Hospital Araba
Vitoria
-
Spain
Research Group on Community Nutrition & Oxidative Stress
University of Balearic Islands
Palma de Mallorca
-
Spain
Virgen de la Victoria Hospital
University of Málaga
Málaga
-
Spain
University of Las Palmas de Gran Canaria
Las Palmas
-
Spain
Biomedicine Institute (IBIOMED)
University of León
Primary Health Care Management of León (Sacyl)
León
-
Spain
Department of Family Medicine
Research Unit
Distrito Sanitario Atención Primaria Sevilla
Sevilla
-
Spain
Department of Endocrinology
Foundation Jiménez-Díaz
Madrid
-
Spain
Lipids and Vascular Risk Unit
Internal Medicine
University Hospital of Bellvitge
Hospitalet de Llobregat
Barcelona
-
Spain
Department of Endocrinology
IDIBAPS
Hospital Clinic
University of Barcelona
Barcelona
-
Spain
Nutritional Genomics and Epigenomics Group
Institute IMDEA-Food
CEI UAM+CSIC
Madrid
-
Spain
Division of Preventive Medicine
University of Jaén
Jaén
-
Spain
Department of Endocrinology and Nutrition
Institute for Health Research Hospital Clínico San Carlos (IdISSC)
Madrid
-
Spain

Sponsor information

European Research Council (Belgium) / The Carlos III Health Institute (Instituto De Salud Carlos III) (Spain)
Other

Place Rogier 16, COV2 24/009 / C. Sinesio Delgado 4
Brussels / Madrid
Belgium / Spain
rtd-erc@ec.europa.eu / oficina.informacion@isciii.es
Brussels / Madrid
BE-1049 / ES 28
Belgium

Website http://erc.europa.eu
ROR logo "ROR" https://ror.org/0472cxd90

Funders

Funder type

Research council

European Research Council Advanced Research Grant (Grant Agreement No.: 340918) (Belgium)
Government organisation / National government
Alternative name(s)
ERC
Instituto de Salud Carlos III
Government organisation / National government
Alternative name(s)
SaludISCIII, InstitutodeSaludCarlosIII, Instituto de Salud Carlos III | Madrid, Spain, Carlos III Institute of Health, Institute of Health Carlos III, Carlos III Health Institute, ISCIII
Location
Spain
Ciberobn, Fis-Coordinated Grant PI13/00462, Rd 06/0045

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planNot provided at time of registration
IPD sharing planThe datasets generated and analyzed during the current study are not expected to be made available outside the core research group, as neither participants’ consent forms or ethics approval included permission for open access. However, the researchers will follow a controlled data sharing collaboration model, as in the informed consent participants agreed with a controlled collaboration with other investigators for research related to the project’s aims. Therefore, investigators who are interested in this study can contact the PREDIMED Plus Steering Committee by sending a request letter to predimed_plus_scommittee@googlegroups.com. A data sharing agreement indicating the characteristics of the collaboration and data management will be completed for the proposals that are approved by the Steering Committee.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 13/11/2018 Yes No
Results article taste perception and genomics results 01/06/2019 23/04/2019 Yes No
Results article results 15/10/2019 16/10/2019 Yes No
Results article results 01/11/2019 Yes No
Results article results 01/02/2020 24/12/2019 Yes No
Results article results 23/12/2019 31/12/2019 Yes No
Results article results 01/05/2019 22/01/2020 Yes No
Results article results 01/10/2020 19/02/2020 Yes No
Results article results 19/02/2020 24/02/2020 Yes No
Results article baseline cross-sectional analysis results 26/02/2020 28/02/2020 Yes No
Results article results 04/01/2021 10/12/2020 Yes No
Results article results 10/12/2020 11/12/2020 Yes No
Results article results 06/01/2021 12/01/2021 Yes No
Results article results 28/01/2021 22/02/2021 Yes No
Results article diet adherence and cardiometabolic risk factors results 01/05/2021 05/05/2021 Yes No
Results article gut microbiome analysis results 21/05/2021 24/05/2021 Yes No
Results article Data-Driven Clustering results 10/06/2021 14/06/2021 Yes No
Results article two-year follow up results 01/06/2021 18/06/2021 Yes No
Results article Validity of the energy-restricted Mediterranean Diet Adherence Screener 06/07/2021 09/08/2021 Yes No
Results article substudy results 28/09/2021 29/09/2021 Yes No
Results article 08/02/2021 05/11/2021 Yes No
Results article 29/10/2021 16/11/2021 Yes No
Results article longitudinal analysis 30/11/2021 01/12/2021 Yes No
Results article Association between cardiovascular risk factors and depression in participants with metabolic syndrome 14/04/2022 Yes No
Results article Role of NAFLD on the Health Related QoL Response to Lifestyle in Patients With Metabolic Syndrome 29/06/2022 19/07/2022 Yes No
Results article Impulsivity is longitudinally associated with healthy and unhealthy dietary patterns in individuals with overweight or obesity and metabolic syndrome within the framework of the PREDIMED-Plus trial 08/08/2022 09/08/2022 Yes No
Results article Association of dietary carbohydrate quality with visceral fat deposition and other adiposity indicators 20/08/2022 12/09/2022 Yes No
Results article Impact of COVID-19 pandemic on the trial 12/01/2023 31/01/2023 Yes No
Results article Increase from low to moderate, but not high, caffeinated coffee consumption is associated with favorable changes in body fat 11/02/2023 06/03/2023 Yes No
Results article Prospective cohort analysis of water intake and hydration status 08/03/2023 08/03/2023 Yes No
Results article Environmental sustainability 24/05/2023 30/05/2023 Yes No
Results article Metabolic syndrome criteria and severity and carbon dioxide (CO2) emissions 13/07/2023 17/07/2023 Yes No
Results article Effect of a 3-year lifestyle intervention on telomere length in participants from PREDIMED-Plus: A randomized trial 10/07/2023 24/07/2023 Yes No
Results article Association of monetary diet cost of foods and diet quality in Spanish older adults 25/07/2023 11/08/2023 Yes No
Results article Association of adiposity with COVID-19 risk in older adults with overweight/obesity and metabolic syndrome 13/10/2023 16/10/2023 Yes No
Results article 02/10/2023 19/10/2023 Yes No
Results article 02/10/2023 19/10/2023 Yes No
Results article Mediterranean diet linked to microbial phenolic metabolites associated with better cognitive performance in an older population 07/12/2023 18/12/2023 Yes No
Results article Effect of 1-year lifestyle intervention with energy-reduced Mediterranean diet and physical activity promotion on the gut metabolome and microbiota: a randomized clinical trial 28/02/2024 04/03/2024 Yes No
Results article Beverage consumption and environmental sustainability 03/03/2024 13/03/2024 Yes No
Results article Associations of Alcohol Consumption With Left Atrial Morphology and Function in a Population at High Cardiovascular Risk 27/03/2024 28/03/2024 Yes No
Results article sex, APOE genotype, endocannabinoids and cognitive change 12/06/2024 25/06/2024 Yes No
Results article Long-term association between water intake and kidney function in a population at high cardiovascular risk 12/08/2024 14/08/2024 Yes No
Results article Body composition and CO2 dietary emissions 17/01/2025 04/02/2025 Yes No
Results article Pasta consumption and cardiometabolic risks 19/02/2025 20/02/2025 Yes No
Results article 17/04/2025 23/04/2025 Yes No

Editorial Notes

23/04/2025: Publication reference added.
20/02/2025: Publication reference added.
04/02/2025: Publication reference added.
14/08/2024: Publication reference added.
25/06/2024: Publication reference added.
28/03/2024: Publication reference added.
13/03/2024: Publication reference added.
04/03/2024: Publication reference added.
18/12/2023: Publication reference added.
19/10/2023: Publication references added.
16/10/2023: Publication reference added.
11/08/2023: Publication reference added.
24/07/2023: Publication reference added.
17/07/2023: Publication reference added.
30/05/2023: Publication reference added.
08/03/2023: Publication reference added.
06/03/2023: Publication reference added.
31/01/2023: Publication reference added.
12/09/2022: Publication reference added.
09/08/2022: Publication reference added.
19/07/2022: Publication reference added.
14/04/2022: Publication reference added.
01/12/2021: Publication reference added.
16/11/2021: Publication reference added.
05/11/2021: Publication reference added.
29/09/2021: Publication reference added.
09/08/2021: Publication reference added.
18/06/2021: Publication reference added.
14/06/2021: Publication reference added.
24/05/2021: Publication reference added.
05/05/2021: Publication reference added.
22/02/2021: Publication reference added.
12/01/2021: Publication reference added.
11/12/2020: Publication reference added.
10/12/2020: Publication reference added.
06/07/2020: IPD sharing statement added.
30/06/2020: The following changes were made to the trial record:
1. The overall trial start date was changed from 01/10/2013 to 05/09/2013.
2. The overall trial end date was changed from 01/05/2020 to 22/12/2024.
28/02/2020: Publication reference added.
24/02/2020: Publication reference added.
19/02/2020: Publication reference added.
22/01/2020: Publication reference added.
31/12/2019: Publication reference added.
24/12/2019: Publication reference added.
16/10/2019: Publication reference added.
15/07/2019: The secondary outcome measures were updated.
23/04/2019: The following changes have been made:
1. Publication reference added.
2. The total final enrolment has been added from the results publication.
06/02/2019: The secondary outcome measures were updated.
08/10/2018: Publication reference added.
04/06/2018: The following changes were made to the trial record:
1. The contact details, interventions, primary and secondary outcome measures, exclusion criteria and trial participating centres were updated.
2. The recruitment dates were added.