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
- 30/06/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
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
Contact information
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 ID |
0000-0003-2700-7459 |
|---|---|
| Phone | +34 (0)977759313 |
| jordi.salas@urv.cat |
Study information
| Study design | Randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Cardiovascular 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 acronym | PREDIMED-Plus |
| Study objectives | An 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 |
| Health condition(s) or problem(s) studied | Cardiovascular disease |
| Intervention | Participants 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 type | Other |
| Primary outcome measure | Current 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 measures | Current 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 date | 05/09/2013 |
| Completion date | 22/12/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Senior |
| Lower age limit | 55 Years |
| Upper age limit | 75 Years |
| Sex | Both |
| Target number of participants | 6000 |
| Total final enrolment | 6874 |
| Key inclusion criteria | 1. 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. |
| Key exclusion criteria | Current 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 |
| Date of first enrolment | 05/09/2013 |
| Date of final enrolment | 05/12/2016 |
Locations
Countries of recruitment
- Spain
Study participating centres
Department of Biochemistry and Biotechnology
Pere Virgili Institute for Health Research
Rovira i Virgili University
Reus
-
Spain
Pamplona
-
Spain
University Jaume I
Conselleria de Sanitat de la Generalitat Valenciana
Valencia
-
Spain
Barcelona
-
Spain
Barcelona
-
Spain
ISABIAL-FISABIO
Alicante
-
Spain
-
Spain
University of Navarra
Pamplona
-
Spain
University of Málaga-IBIMA
Málaga
-
Spain
Maimonides Biomedical Research Institute of Cordoba (IMIBIC)
Reina Sofia University Hospital
University of Cordoba
Cordoba
-
Spain
Hospital Clínic
University of Barcelona
Barcelona
-
Spain
Granada
-
Spain
-
Spain
Palma de Mallorca
-
Spain
Málaga
-
Spain
-
Spain
Primary Health Care Management of León (Sacyl)
León
-
Spain
Distrito Sanitario Atención Primaria Sevilla
Sevilla
-
Spain
Madrid
-
Spain
University Hospital of Bellvitge
Hospitalet de Llobregat
Barcelona
-
Spain
Hospital Clinic
University of Barcelona
Barcelona
-
Spain
CEI UAM+CSIC
Madrid
-
Spain
Jaén
-
Spain
Madrid
-
Spain
Sponsor information
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" |
https://ror.org/0472cxd90 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- ERC
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
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | The 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 | |
| Protocol file | 03/04/2018 | 30/06/2025 | No | No | |
| Results article | Secondary analysis of bone mineral density | 01/04/2025 | 30/06/2025 | Yes | No |
| Statistical Analysis Plan | version 2 | 31/07/2019 | 30/06/2025 | No | No |
Additional files
Editorial Notes
30/06/2025: Publication reference added; SAP and protocol files uploaded.
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.
