TY - JOUR AU - Jäger, Susanne AU - Kuxhaus, Olga AU - Prada, Marcela AU - Huybrechts, Inge AU - Tong, Tammy Y N AU - Forouhi, Nita G AU - Razquin, Cristina AU - Corella, Dolores AU - Martinez-Gonzalez, Miguel A AU - Dahm, Christina C AU - Ibsen, Daniel B AU - Tjønneland, Anne AU - Halkjær, Jytte AU - Marques, Chloé AU - Cadeau, Claire AU - Ren, Xuan AU - Katzke, Verena AU - Bendinelli, Benedetta AU - Agnoli, Claudia AU - Catalano, Alberto AU - Farràs, Marta AU - Sánchez, Maria-Jose AU - López, María Dolores Chirlaque AU - Guevara, Marcela AU - Aune, Dagfinn AU - Sharp, Stephen J AU - Wareham, Nicholas J AU - Schulze, Matthias B TI - 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. JO - BMC medicine VL - 23 IS - 1 SN - 1741-7015 CY - London PB - BioMed Central M1 - DKFZ-2025-01175 SP - 344 PY - 2025 AB - 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.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.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 KW - Humans KW - Diabetes Mellitus, Type 2: genetics KW - Diabetes Mellitus, Type 2: blood KW - Diabetes Mellitus, Type 2: epidemiology KW - Fatty Acid Desaturases: genetics KW - Delta-5 Fatty Acid Desaturase KW - alpha-Linolenic Acid: administration & dosage KW - Male KW - Female KW - Linoleic Acid: administration & dosage KW - Linoleic Acid: blood KW - Middle Aged KW - Aged KW - Nuts KW - Fatty Acids: blood KW - Cohort Studies KW - Polymorphism, Single Nucleotide KW - Risk Factors KW - Cohort study (Other) KW - Fatty acid desaturase (Other) KW - Plasma phospholipid fatty acids (Other) KW - Polyunsaturated fatty acids (Other) KW - Randomized controlled trial (Other) KW - Fatty Acid Desaturases (NLM Chemicals) KW - Delta-5 Fatty Acid Desaturase (NLM Chemicals) KW - FADS1 protein, human (NLM Chemicals) KW - alpha-Linolenic Acid (NLM Chemicals) KW - Linoleic Acid (NLM Chemicals) KW - Fatty Acids (NLM Chemicals) LB - PUB:(DE-HGF)16 C6 - pmid:40484934 DO - DOI:10.1186/s12916-025-04187-8 UR - https://inrepo02.dkfz.de/record/301905 ER -