Nut consumption, linoleic and α-linolenic acid intakes, and genetics: how fatty acid desaturase 1 impacts plasma fatty acids and type 2 diabetes risk in EPIC-InterAct and PREDIMED studies

Abstract Background Dietary guidelines recommend replacing saturated fatty acid with unsaturated fats, particularly polyunsaturated fatty acids. Cohort studies do not suggest a clear benefit of higher intake of polyunsaturated fatty acids but, in contrast, higher circulating linoleic acid (LA) level...

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Main Authors: Susanne Jäger, Olga Kuxhaus, Marcela Prada, Inge Huybrechts, Tammy Y. N. Tong, Nita G. Forouhi, Cristina Razquin, Dolores Corella, Miguel A. Martinez-Gonzalez, Christina C. Dahm, Daniel B. Ibsen, Anne Tjønneland, Jytte Halkjær, Chloé Marques, Claire Cadeau, Xuan Ren, Verena Katzke, Benedetta Bendinelli, Claudia Agnoli, Alberto Catalano, Marta Farràs, Maria-Jose Sánchez, María Dolores Chirlaque López, Marcela Guevara, Dagfinn Aune, Stephen J. Sharp, Nicholas J. Wareham, Matthias B. Schulze
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Language:English
Published: BMC 2025-06-01
Series:BMC Medicine
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Online Access:https://doi.org/10.1186/s12916-025-04187-8
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author Susanne Jäger
Olga Kuxhaus
Marcela Prada
Inge Huybrechts
Tammy Y. N. Tong
Nita G. Forouhi
Cristina Razquin
Dolores Corella
Miguel A. Martinez-Gonzalez
Christina C. Dahm
Daniel B. Ibsen
Anne Tjønneland
Jytte Halkjær
Chloé Marques
Claire Cadeau
Xuan Ren
Verena Katzke
Benedetta Bendinelli
Claudia Agnoli
Alberto Catalano
Marta Farràs
Maria-Jose Sánchez
María Dolores Chirlaque López
Marcela Guevara
Dagfinn Aune
Stephen J. Sharp
Nicholas J. Wareham
Matthias B. Schulze
author_facet Susanne Jäger
Olga Kuxhaus
Marcela Prada
Inge Huybrechts
Tammy Y. N. Tong
Nita G. Forouhi
Cristina Razquin
Dolores Corella
Miguel A. Martinez-Gonzalez
Christina C. Dahm
Daniel B. Ibsen
Anne Tjønneland
Jytte Halkjær
Chloé Marques
Claire Cadeau
Xuan Ren
Verena Katzke
Benedetta Bendinelli
Claudia Agnoli
Alberto Catalano
Marta Farràs
Maria-Jose Sánchez
María Dolores Chirlaque López
Marcela Guevara
Dagfinn Aune
Stephen J. Sharp
Nicholas J. Wareham
Matthias B. Schulze
author_sort Susanne Jäger
collection DOAJ
description Abstract Background Dietary guidelines recommend replacing saturated fatty acid with unsaturated fats, particularly polyunsaturated fatty acids. Cohort studies do not suggest a clear benefit of higher intake of polyunsaturated fatty acids but, in contrast, higher circulating linoleic acid (LA) levels—reflective of dietary LA intake, are associated with a reduced risk of type 2 diabetes. However, genetic variants in the fatty acid desaturase 1 gene (FADS1) may influence individual responses to plant-based fats. We explored whether FADS1 variants influence the relationships of LA and α-linolenic acid (ALA) intakes and nut consumption with plasma phospholipid fatty acid profiles and type 2 diabetes risk in a large-scale cohort study and a randomized controlled trial. Methods In the EPIC-InterAct case-cohort (7,498 type 2 diabetes cases, 10,087 subcohort participants), we investigated interactions of dietary and plasma phospholipid fatty acids and nut consumption with FADS1 rs174547 in relation to incident type 2 diabetes using weighted Cox regression. In PREDIMED (492 participants in the Mediterranean Diet + Nuts intervention group, 436 participants in the control group), we compared changes in plasma phospholipid FAs from baseline to year 1. Results In EPIC-InterAct and PREDIMED, nut consumption was positively associated with LA plasma levels and inversely with arachidonic acid, the latter becoming stronger with increasing number of the minor rs174547 C allele (p interaction EPIC-InterAct: 0.030, PREDIMED: 0.003). Although the inverse association of nut consumption with diabetes seemed stronger in participants with rs174547 CC-genotype (HR: 0.73, 95% CI: 0.54–1.00) compared with CT (0.94, 0.81–1.10) or TT (0.90, 0.78–1.05) in EPIC-InterAct, this interaction was not statistically significant. Conclusions FADS1 variation modified the effect of nut consumption on circulating FAs. We did not observe clear evidence that it modified the association between nut consumption and type 2 diabetes risk.
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spelling doaj-art-ceca01b0f5ba46b1a2db2d7bdc5036892025-08-20T03:21:03ZengBMCBMC Medicine1741-70152025-06-0123111110.1186/s12916-025-04187-8Nut consumption, linoleic and α-linolenic acid intakes, and genetics: how fatty acid desaturase 1 impacts plasma fatty acids and type 2 diabetes risk in EPIC-InterAct and PREDIMED studiesSusanne Jäger0Olga Kuxhaus1Marcela Prada2Inge Huybrechts3Tammy Y. N. Tong4Nita G. Forouhi5Cristina Razquin6Dolores Corella7Miguel A. Martinez-Gonzalez8Christina C. Dahm9Daniel B. Ibsen10Anne Tjønneland11Jytte Halkjær12Chloé Marques13Claire Cadeau14Xuan Ren15Verena Katzke16Benedetta Bendinelli17Claudia Agnoli18Alberto Catalano19Marta Farràs20Maria-Jose Sánchez21María Dolores Chirlaque López22Marcela Guevara23Dagfinn Aune24Stephen J. Sharp25Nicholas J. Wareham26Matthias B. Schulze27Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-RehbrueckeDepartment of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-RehbrueckeDepartment of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-RehbrueckeInternational Agency for Research on Cancer, World Health OrganizationNuffield Department of Population Health, Cancer Epidemiology Unit, University of OxfordMedical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical CampusDepartment of Preventive Medicine and Public Health, University of Navarra, IdiSNA (Instituto de Investigación Sanitaria de Navarra)Department of Preventive Medicine and Public Health, School of Medicine, University of ValenciaDepartment of Preventive Medicine and Public Health, University of Navarra, IdiSNA (Instituto de Investigación Sanitaria de Navarra)Department of Public Health, Aarhus UniversityDepartment of Public Health, Aarhus UniversityDanish Cancer Institute, Diet, Cancer and HealthDanish Cancer Institute, Diet, Cancer and HealthParis-Saclay University, UVSQ, Inserm, Gustave Roussy, CESPParis-Saclay University, UVSQ, Inserm, Gustave Roussy, CESPParis-Saclay University, UVSQ, Inserm, Gustave Roussy, CESPDivision of Cancer Epidemiology, German Cancer Research Center, DKFZClinical Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO)Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei TumoriDepartment of Translational Medicine, University of Piemonte OrientaleUnit of Nutrition and Cancer, Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL)Escuela Andaluza de Salud Pública (EASP)Department of Epidemiology, IMIB-Arrixaca, Regional Health Council, Murcia UniversityCentro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)Department of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonMedical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical CampusMedical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical CampusDepartment of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-RehbrueckeAbstract Background Dietary guidelines recommend replacing saturated fatty acid with unsaturated fats, particularly polyunsaturated fatty acids. Cohort studies do not suggest a clear benefit of higher intake of polyunsaturated fatty acids but, in contrast, higher circulating linoleic acid (LA) levels—reflective of dietary LA intake, are associated with a reduced risk of type 2 diabetes. However, genetic variants in the fatty acid desaturase 1 gene (FADS1) may influence individual responses to plant-based fats. We explored whether FADS1 variants influence the relationships of LA and α-linolenic acid (ALA) intakes and nut consumption with plasma phospholipid fatty acid profiles and type 2 diabetes risk in a large-scale cohort study and a randomized controlled trial. Methods In the EPIC-InterAct case-cohort (7,498 type 2 diabetes cases, 10,087 subcohort participants), we investigated interactions of dietary and plasma phospholipid fatty acids and nut consumption with FADS1 rs174547 in relation to incident type 2 diabetes using weighted Cox regression. In PREDIMED (492 participants in the Mediterranean Diet + Nuts intervention group, 436 participants in the control group), we compared changes in plasma phospholipid FAs from baseline to year 1. Results In EPIC-InterAct and PREDIMED, nut consumption was positively associated with LA plasma levels and inversely with arachidonic acid, the latter becoming stronger with increasing number of the minor rs174547 C allele (p interaction EPIC-InterAct: 0.030, PREDIMED: 0.003). Although the inverse association of nut consumption with diabetes seemed stronger in participants with rs174547 CC-genotype (HR: 0.73, 95% CI: 0.54–1.00) compared with CT (0.94, 0.81–1.10) or TT (0.90, 0.78–1.05) in EPIC-InterAct, this interaction was not statistically significant. Conclusions FADS1 variation modified the effect of nut consumption on circulating FAs. We did not observe clear evidence that it modified the association between nut consumption and type 2 diabetes risk.https://doi.org/10.1186/s12916-025-04187-8Polyunsaturated fatty acidsFatty acid desaturasePlasma phospholipid fatty acidsCohort studyRandomized controlled trial
spellingShingle Susanne Jäger
Olga Kuxhaus
Marcela Prada
Inge Huybrechts
Tammy Y. N. Tong
Nita G. Forouhi
Cristina Razquin
Dolores Corella
Miguel A. Martinez-Gonzalez
Christina C. Dahm
Daniel B. Ibsen
Anne Tjønneland
Jytte Halkjær
Chloé Marques
Claire Cadeau
Xuan Ren
Verena Katzke
Benedetta Bendinelli
Claudia Agnoli
Alberto Catalano
Marta Farràs
Maria-Jose Sánchez
María Dolores Chirlaque López
Marcela Guevara
Dagfinn Aune
Stephen J. Sharp
Nicholas J. Wareham
Matthias B. Schulze
Nut consumption, linoleic and α-linolenic acid intakes, and genetics: how fatty acid desaturase 1 impacts plasma fatty acids and type 2 diabetes risk in EPIC-InterAct and PREDIMED studies
BMC Medicine
Polyunsaturated fatty acids
Fatty acid desaturase
Plasma phospholipid fatty acids
Cohort study
Randomized controlled trial
title Nut consumption, linoleic and α-linolenic acid intakes, and genetics: how fatty acid desaturase 1 impacts plasma fatty acids and type 2 diabetes risk in EPIC-InterAct and PREDIMED studies
title_full Nut consumption, linoleic and α-linolenic acid intakes, and genetics: how fatty acid desaturase 1 impacts plasma fatty acids and type 2 diabetes risk in EPIC-InterAct and PREDIMED studies
title_fullStr Nut consumption, linoleic and α-linolenic acid intakes, and genetics: how fatty acid desaturase 1 impacts plasma fatty acids and type 2 diabetes risk in EPIC-InterAct and PREDIMED studies
title_full_unstemmed Nut consumption, linoleic and α-linolenic acid intakes, and genetics: how fatty acid desaturase 1 impacts plasma fatty acids and type 2 diabetes risk in EPIC-InterAct and PREDIMED studies
title_short Nut consumption, linoleic and α-linolenic acid intakes, and genetics: how fatty acid desaturase 1 impacts plasma fatty acids and type 2 diabetes risk in EPIC-InterAct and PREDIMED studies
title_sort nut consumption linoleic and α linolenic acid intakes and genetics how fatty acid desaturase 1 impacts plasma fatty acids and type 2 diabetes risk in epic interact and predimed studies
topic Polyunsaturated fatty acids
Fatty acid desaturase
Plasma phospholipid fatty acids
Cohort study
Randomized controlled trial
url https://doi.org/10.1186/s12916-025-04187-8
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