Interaction of Chronic Daily Headache, Dietary Intake of Iron, and Fto Genotype Publisher Pubmed



Shekari Y ; Mahmoodi Z ; Ghorbani Hesari M ; Bahmani P ; Abdoli Rezaei S ; Parhiz A ; Mirshafaei MA ; Fahimzad FS ; Varmazyar F ; Doaei S ; Gholamalizadeh M
Source: Molecular Pain Published:2026

Abstract

Background: Chronic daily headache (CDH) is known to be a common and debilitating disease that is influenced by genetic, dietary, and lifestyle factors. Iron (Fe) plays a key role in energy metabolism and neurotransmitter synthesis, while the FTO gene polymorphism (rs9939609) may play a role in modulating nutritional responses and nutrient metabolism. This study aimed to determine the interaction between CDH odds, dietary iron intake, and FTO genotype. Methods: This case-control study was conducted on 150 CDH patients and 150 healthy individuals aged 40–80 years. Participants were assessed for anthropometric measurements, assessment of food intake using a validated food frequency questionnaire, and FTO genotype. The association between dietary iron intake and CDH stratified by FTO genotype was assessed using logistic regression analysis after adjusting for age, gender, body mass index (BMI), physical activity, energy intake, and hypertension. Results: Among individuals with AT/AA genotypes, those with CDH had lower dietary iron intake than controls (17.10 ± 4.02 vs 18.63 ± 4.62 mg/day, p = 0.023). Logistic regression after full adjustment found an inverse association between dietary iron and CDH in AT/AA genotype carriers (p = 0.042). No significant association was observed in TT genotype carriers. Conclusion: Dietary iron intake may be associated with a reduced odds of CDH in FTO A allele carriers, but no association was observed in TT genotype carriers, suggesting a gene-nutrient interaction in the prevention and management of CDH. Further studies are necessary to substantiate these findings. © The Author(s) 2026. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).