Acknowledgments: We thank all the volunteers for the participation and personnel for the contribution in the PREDIMED-Plus trial. We also thank all the investigators of the PREDIMED-Plus study (supplemental Material). CIBEROBN (Centros de Investigación Biomédica en Red: Obesidad y Nutrición), CIBERESP (Centros de Investigación Biomédica en Red: Epidemiología y Salud Pública) and CIBERDEM (Centros de Investigación Biomédica en Red: Diabetes y Enfermedades Metabólicas asociadas) are initiatives of ISCIII, Madrid, Spain. The authors also thank the PREDIMED-Plus Biobank Network as a part of the National Biobank Platform of the ISCIII for storing and managing the PREDIMED-Plus biological samples. Food companies Hojiblanca (Lucena, Spain) and Patrimonio Comunal Olivarero (Madrid, Spain) donated extra virgin olive oil, and the Almond Board of California (Modesto, CA), American Pistachio Growers (Fresno, CA), and Paramount Farms (Wonderful Company, LLC, Los Angeles, CA) donated nuts. Jordi Salas-Salvadó gratefully acknowledges the financial support by ICREA under the ICREA Academia programme.
Funding: This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (five coordinated FIS projects leaded by JS-S and JVi, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926; PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332); the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to JS-S; the European Research Council (Advanced Research Grant 2014–2019; agreement #340918) granted to MÁM-G.; the Recercaixa (number 2013ACUP00194) grant to JS-S; grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018); the PROMETEO/2017/017 grant from the Generalitat Valenciana; the SEMERGEN grant; funds from the European Regional Development Fund (CB06/03); International Nut & Dried Fruit Council – FESNAD (Long-term effects of an energy-restricted Mediterranean diet on mortality and cardiovascular disease 2014 –2015, No. 201302) (PI: MÁM-G); the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 (PI: DR); grant of support to research groups no. 35/2011 (Balearic Islands Gov.; FEDER funds) (JAT and CB); the JR17/00022 (ISCIII) grant to OC; the Boosting young talent call grant program for the development of IISPV research projects 2019–2021 (Ref.: 2019/IISPV/03 grant to AD-L); the Societat Catalana d'Endocrinologia i Nutrició (SCEN) Clinical-Research Grant 2019 (IPs: JS-S and AD-L). Collaborative Nutrition and/or Obesity Project for Young Researchers 2019 supported by CIBEROBN entitled: Lifestyle Interventions and Chronic Kidney Disease: Inflammation, Oxidative Stress and Metabolomic Profile (LIKIDI study) grant to AD-L. None of the funding sources took part in the design, collection, analysis, interpretation of the data, or writing the report, or in the decision to submit the manuscript for publication.
Competing interests: Dr Salas-Salvado reported receiving research support from the Instituto de Salud Carlos III (ISCIII), Ministerio de Educación y Ciencia, Departament de Salut Pública de la Generalitat de Catalunya, the European Commission, the California Walnut Commission, Patrimonio Comunal Olivarero, La Morella Nuts, and Borges S.A; receiving consulting fees or travel expenses from Danone, California Walnut Commission, Eroski Foundation, Instituto Danone, Nestle, Nuts for Life, and Abbott Laboratories, receiving nonfinancial support from Hojiblanca, Patrimonio Comunal Olivarero, and Almond Board of California; serving on the board of and receiving grant support through his institution from the International Nut and Dried Foundation and the Eroski Foundation; and grants and personal fees from Instituto Danone. No other disclosures were reported. Dr Ros reported receiving grants, personal fees, and nonfinancial support from the CaliforniaWalnut Commission during the conduct of the study and grants, personal fees, nonfinancial support from Alexion; grants from Amgen and Pfizer; grants and personal fees from Sanofi Aventis; personal fees and nonfinancial support from Ferrer International, Danone, and Merck Sharp & Dohme; and personal fees from Amarin outside the submitted work. Dr Corella reported receiving grants from ISCIII during the conduct of the study. Dr Fitó reported receiving grants from ISCIII during the conduct of the study. Dr Romaguera reported receiving grants from ISCIII during the conduct of the study and grants from Fundación AstraZeneca outside the submitted work. Dr Vioque reported receiving grants from ISCIII during the conduct of the study. Dr Alonso-Gómez reported receiving grants from ISCIII during the conduct of the study. Dr Wärnberg reported receiving grants from ISCIII during the conduct of the study. Dr Martínez reported receiving grants from ISCIII during the conduct of the study. Dr Serra-Majem reported receiving grants from ISCIII during the conduct of the study. Dr Estruch reported receiving grants from Instituto de Salud Carlos III and olive oil for the trial from Fundacion Patrimonio Comunal Olivarero\during the conduct of the study and personal fees from Brewers of Europe, Fundación Cerveza y Salud, Interprofesional del Aceite de Oliva, Instituto Cervantes, Pernaud Richar, Fundación Dieta Mediterránea, Wine and Culinary International Forum; nonfinancial support from Sociedad Española de Nutrición and Fundación Bosch y Gimpera; and grants from Uriach Laboratories outside the submitted work. Dr Tinahones reported receiving grants from ISCIII during the conduct of the study. Dr Lapetra reported receiving grants from ISCIII during the conduct of the study. Dr Pintó reported receiving grants from ISCIII during the conduct of the study; receiving consulting fees from Sanofi Aventis, Amgen, and Abbott laboratories; receiving lecture personal fees from Esteve, Lacer and Rubio laboratories. Dr Tur reported receiving grants from ISCIII during the conduct of the study. Dr López-Miranda reported receiving grants from ISCIII during the conduct of the study. Dr Delgado-Rodríguez reported receiving grants from ISCIII during the conduct of the study; grants from the Diputación Provincial de Jaén and the Caja Rural de Jaén. Dr Matía-Martín reported receiving grants from ISCIII during the conduct of the study; personal fees from Organización Interprofesional Láctea outside the submitted work. Dr Damiel Martín reported receiving grants from Fundación Cerveza y Salud. Dr Vidal reported receiving grants from ISCIII during the conduct of the study. Dr Martínez-González reported receiving grants from ISCIII during the conduct of the study. All other authors declare no competing interests.
Authors’ contributions: DC, MoF, DR, JV, AMA-G, JW, JAM, LS-M, RE, FJT, JL, XP, JAT, JLM, MD-R, PM, LD, JV, CV, ER, MAM-G, and JS-S, designed the research. AD-L, NB-T, VR, ET, NB, DC, MoF, DR, JV, AMA-G, JW, JAM, LS-M, RE, FJT, JL, XP, JAT, JLM, NCI, MD-R, PM, LD, JAP, JV, CV, ER, MR-C, JVS, AG, MF, MGH, LTS, NP-F, MAZ, AS-V, ES, JCF-G, JMS-L, MGG, MMB, JD-E, CO-A, OC, MM, LT-C, CSS, MAM, MAM-G, and JS-S conducted the research. AD-L, and JS-S, analysed the data. AD-L, and JS-S, wrote the article. All authors revised the manuscript for important intellectual content and read and approved the final manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. AD-L, and JS-S, are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Availability of data and materials: The dataset (including data dictionaries) of PREDIMED-Plus is available to external investigators in order to make possible the replication of the main analyses used for the published article. However, due to the restrictions imposed by the Informed Consent and the Institutional Review Boards (IRB), bona fide investigators interested in analyzing the PREDIMED-Plus dataset may submit a brief proposal and statistical analysis plan to the corresponding author (JS-S) at [email protected]. Upon approval from the Steering Committee and IRBs, the data will be made available to them using an onsite secure access data enclave. The study protocol is available at http://predimedplus.com/.
Ethics approval and consent to participate: The study protocol and procedures were approved according to the ethical standards of the Declaration of Helsinki by the Institutional Review Boards (IRBs) of all the participating institutions: CEI Provincial de Málaga, CEI de los Hospitales Universitarios Virgen Macarena y Virgen del Rocío, CEI de la Universidad de Navarra, CEI de las Illes Balears, CEIC del Hospital Clínic de Barcelona, CEIC del Parc de Salut Mar, CEIC del Hospital Universitari Sant Joan de Reus, CEI del Hospital Universitario San Cecilio, CEIC de la Fundación Jiménez Díaz, CEIC Euskadi, CEI en Humanos de la Universidad de Valencia, CEIC del Hospital Universitario de Gran Canaria Doctor Negrín, CEIC del Hospital Universitario de Bellvitge, CEIC de IMDEA Alimentación, CEIC del Hospital Clínico San Carlos, CEI Provincial de Málaga, CCEIBA de la Investigación Biomédica de Andalucía, CEIC del Hospital General Universitario de Elche, Comité de Ética del Hospital Universitario Reina Sofía and CEIC de León. All participants provided informed written consent.
Consent for publication: Not applicable.