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Dietary folate intake and metabolic syndrome in participants of PREDIMED-Plus study: a cross-sectional study

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A Correction to this article was published on 05 December 2020

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Abstract

Purpose

We examined the association between dietary folate intake and a score of MetS (metabolic syndrome) and its components among older adults at higher cardiometabolic risk participating in the PREDIMED-Plus trial.

Methods

A cross-sectional analysis with 6633 with overweight/obesity participants with MetS was conducted. Folate intake (per 100 mcg/day and in quintiles) was estimated using a validated food frequency questionnaire. We calculated a MetS score using the standardized values as shown in the formula: [(body mass index + waist-to-height ratio)/2] + [(systolic blood pressure + diastolic blood pressure)/2] + plasma fasting glucose–HDL cholesterol + plasma triglycerides. The MetS score as continuous variable and its seven components were the outcome variables. Multiple robust linear regression using MM-type estimator was performed to evaluate the association adjusting for potential confounders.

Results

We observed that an increase in energy-adjusted folate intake was associated with a reduction of MetS score (β for 100 mcg/day = − 0.12; 95% CI: − 0.19 to − 0.05), and plasma fasting glucose (β = − 0.03; 95% CI: − 0.05 to − 0.02) independently of the adherence to Mediterranean diet and other potential confounders. We also found a positive association with HDL-cholesterol (β = 0.07; 95% CI: 0.04–0.10). These associations were also observed when quintiles of energy-adjusted folate intake were used instead.

Conclusion

This study suggests that a higher folate intake may be associated with a lower MetS score in older adults, a lower plasma fasting glucose, and a greater HDL cholesterol in high-risk cardio-metabolic subjects.

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Acknowledgements

We thank all PREDIMED-Plus participants and researchers. CIBEROBN, CIBERESP, and CIBERDEM are initiatives of the Instituto de Salud Carlos III (ISCIII), Madrid, Spain. The Hojiblanca (Lucena, Spain) and Patrimonio Comunal Olivarero (Madrid, Spain) food companies donated extra-virgin olive oil. 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 from the ICREA Academia programme. Thanks to Desirée Valera-Gran for her help with the first draft English-language version. We like to acknowledge Emily Felt for providing assistance with the English revision of the paper; she received compensation.

Funding

The PREDIMED-Plus trial was supported by grants from the Instituto de Salud Carlos III, co-financed by the Fondo Europeo de Desarrollo Regional-FEDER 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, 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, and PI17/00926; the Cohorte PREDIMED-Plus grant; the European Research Council (Advanced Research Grant 2013–2018, 340918) to M.Á.M.-G., the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to J.S.-S., the Recercaixa grant to J.S.-S. (2013ACUP00194), grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018), a grant from the Generalitat Valenciana (PROMETEO/2017/017), a SEMERGEN grant, and funds from the European Regional Development Fund (CB06/03 and CB12/03), The International Nut & Dried Fruit Council—FESNAD (Long-term effects of an energy-restricted Mediterranean diet on mortality and cardiovascular disease 2014–2015, No. 201302) [M.A.M.-G.]; the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 [D.R.], EU-COST Action CA16112, Grant of support to research groups no. 35/2011 from the Balearic Islands Government, Grants from Balearic Islands Health Research Institute (IDISBA). This work is partially supported by ICREA under the ICREA Academia programme. None of the funding sources took part in the design, collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Grupo de Investigación en Terapia Ocupacional (InTeO), Department of Surgery and Pathology, Miguel Hernández University, 03550, Alicante, Spain

    Eva-Maria Navarrete-Muñoz

  2. CIBER de Epidemiología y Salud Pública (CIBERESP), Institute of Health Carlos III, Madrid, Spain

    Jesus Vioque, Aurora Bueno-Cavanillas, Vicente Martín Sánchez & Manoli García-de-la-Hera

  3. Nutritional Epidemiology Unit, Universidad Miguel Hernández, ISABIAL-UMH, Alicante, Spain

    Jesus Vioque, Alejando Oncina-Canovas, Laura Compañ-Gabucio & Manoli García-de-la-Hera

  4. Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Institute of Health Carlos III, Madrid, Spain

    Estefanía Toledo, Miguel Ángel Martínez-González, Jordi Salas-Salvadó, Dolores Corella, Montserrat Fitó, Dora Romaguera, Ángel M. Alonso-Gómez, Julia Wärnberg, J. Alfredo Martínez, Luís Serra-Majem, Ramon Estruch, Francisco J. Tinahones, José Lapetra, Xavier Pintó, Josep A. Tur, José López-Miranda, Ana Isabel de Cos Blanco, Emili Ros, Javier Diez-Espino, Nancy Babio, Rebeca Fernandez-Carrion, Olga Castañer, Edelys Crespo-Oliva, Itziar Abete, Laura Tomaino, Rosa Casas, José Carlos Fernandez-Garcia, José Manuel Santos-Lozano, José M. Gámez, José M. Antonio Garcia-Rios, Miguel Ruiz-Canela, Andrés Díaz-López, Raul Martinez-Lacruz, Maria Dolors Zomeño, Silvia Canudas & Albert Goday

  5. Department of Preventive Medicine and Public Health, University of Navarra, IdiSNA, Pamplona, Spain

    Estefanía Toledo, Miguel Ángel Martínez-González, Javier Diez-Espino & Miguel Ruiz-Canela

  6. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Miguel Ángel Martínez-González

  7. Departament de Bioquímica i Biotecnologia, Unitat de Nutrició, Universitat Rovira i Virgili, Reus, Spain

    Jordi Salas-Salvadó, Nancy Babio, Andrés Díaz-López & Silvia Canudas

  8. Nutrition Unit, University Hospital of Sant Joan de Reus, Reus, Spain

    Jordi Salas-Salvadó, Nancy Babio, Andrés Díaz-López & Silvia Canudas

  9. Institut d’Investigació Sanitària Pere Virgili (IISPV), Reus, Spain

    Jordi Salas-Salvadó, Nancy Babio, Andrés Díaz-López & Silvia Canudas

  10. Department of Preventive Medicine, University of Valencia, Valencia, Spain

    Dolores Corella, Rebeca Fernandez-Carrion & Raul Martinez-Lacruz

  11. Unit of Cardiovascular Risk and Nutrition, Institut Hospital del Mar de Investigaciones Médicas Municipal d’Investigació Médica (IMIM), Barcelona, Spain

    Montserrat Fitó, Olga Castañer, Maria Dolors Zomeño & Albert Goday

  12. Health Research Institute of the Balearic Islands (IdISBa), University Hospital Son Espases, Palma de Mallorca, Spain

    Dora Romaguera, Josep A. Tur, Antoni Colom, José M. Gámez & Elena Rayó

  13. Bioaraba Health Research Institute, Osakidetza Basque Health Service, Araba University Hospital, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain

    Ángel M. Alonso-Gómez & Itziar Salaverria Lete

  14. Department of Nursing, School of Health Sciences, University of Málaga-Institute of Biomedical Research in Malaga (IBIMA), Málaga, Spain

    Julia Wärnberg & Edelys Crespo-Oliva

  15. Department of Nutrition, Food Sciences, and Physiology, Center for Nutrition Research, University of Navarra, Pamplona, Spain

    J. Alfredo Martínez & Itziar Abete

  16. Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria and Centro Hospitalario Universitario Insular Materno Infantil (CHUIMI), Canarian Health Service, Las Palmas de Gran Canaria, Spain

    Luís Serra-Majem & Laura Tomaino

  17. Department of Internal Medicine, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain

    Ramon Estruch & Rosa Casas

  18. Department of Endocrinology, Instituto de Investigación Biomédica de Málaga (IBIMA), Virgen de la Victoria Hospital, University of Málaga, Málaga, Spain

    Francisco J. Tinahones & José Carlos Fernandez-Garcia

  19. Department of Family Medicine, Research Unit, Distrito Sanitario Atención Primaria Sevilla, Sevilla, Spain

    José Lapetra & José Manuel Santos-Lozano

  20. Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain

    Xavier Pintó & Iziar Sarasa

  21. Research Group on Community Nutrition and Oxidative Stress, University of Balearic Islands, Palma de Mallorca, Spain

    Josep A. Tur & José M. Gámez

  22. Department of Internal Medicine, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain

    José López-Miranda & José M. Antonio Garcia-Rios

  23. Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain

    Aurora Bueno-Cavanillas & Sandra Martín-Pelaez

  24. Department of Endocrinology and Nutrition, Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC), Madrid, Spain

    Pilar Matía-Martín

  25. Nutritional Control of the Epigenom Group, Precision Nutrition and Obesity Program, IMDEA Food, CEI UAM + CSIC, Madrid, Spain

    Lidia Daimiel

  26. Institute of Biomedicine (IBIOMED), University of León, León, Spain

    Vicente Martín Sánchez

  27. CIBER Diabetes y Enfermedades Metabólicas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain

    Josep Vidal

  28. Department of Endocrinology, Institut d’Investigacions Biomédiques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain

    Josep Vidal

  29. Department of Endocrinology and Nutrition, Hospital Fundación Jimenez Díaz, Instituto de Investigaciones Biomédicas IISFJD, University Autonoma, Madrid, Spain

    Ana Isabel de Cos Blanco

  30. Lipid Clinic, Department of Endocrinology and Nutrition, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain

    Emili Ros

  31. Gerencia de Atención Primaria, Servicio Navarro de Salud-Osasunbidea, Pamplona, Spain

    Javier Diez-Espino

  32. Department of Clinical and Community Health (DISCCO), Università degli Studi di Milano, Milan, Italy

    Laura Tomaino

  33. Centro Salud San Vicente del Raspeig, Alicante, Spain

    Cristina Gisbert Sellés

  34. Departamento Salud Pública, Campus San Juan, Universidad Miguel Hernández, Ctra. Nacional 332 s/n, 03550, Sant Joan d’Alacant, Spain

    Jesus Vioque

  35. Department of Cardiology, Hospital Son Llàtzer, 07198, Palma de Mallorca, Spain

    José M. Gámez

Authors
  1. Eva-Maria Navarrete-Muñoz
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  2. Jesus Vioque
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  3. Estefanía Toledo
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  4. Alejando Oncina-Canovas
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  5. Miguel Ángel Martínez-González
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  6. Jordi Salas-Salvadó
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  7. Dolores Corella
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Contributions

ENM-M and JV conducted the statistical analyses and drafted the article. All authors contributed substantially to the acquisition of data or analysis and interpretation of data. All authors revised the article critically for important intellectual content. All authors approved the final version to be published.

Corresponding author

Correspondence to Jesus Vioque.

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Conflict of interest

J.S.-S. reports serving on the board of the International Nut and Dried Fruit Council from which he has also received grant support through his institution, receiving consulting fees from Danone, Font Vella Lanjaron, Nuts for Life, and Eroski, and being given grant support through his institution from Eroski. J.S.-S is a member of the executive committee of the Instituto Danone Spain and a member of the scientific committee of the Institute Danone International. L.D. reports receiving a grant from the Fundación Cerveza y Salud. N-B. declares that she received payments from Danone S.A. for the purposes of scientific and technical consulting but not for preparing this study and grant support through his institution from Font Vella Lanjaron. No other potential conflicts of interest relevant to this article were reported.

Ethical approval

All participants provided written informed consent, and the study protocol and procedures were approved according to the ethical standards of the Declaration of Helsinki.

Additional information

The original online version of this article was revised: José M Gámez was not listed among the authors.

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Cite this article

Navarrete-Muñoz, EM., Vioque, J., Toledo, E. et al. Dietary folate intake and metabolic syndrome in participants of PREDIMED-Plus study: a cross-sectional study. Eur J Nutr 60, 1125–1136 (2021). https://doi.org/10.1007/s00394-020-02364-4

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  • DOI: https://doi.org/10.1007/s00394-020-02364-4

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