Background <p>Despite its prevalence, Familial Mediterranean Fever (FMF) remains poorly understood, with limited therapeutic options available to manage its debilitating symptoms. The discovery of a potential link between FMF and dietary components has sparked new hope for personalized nutritional interventions, yet the complex interplay between genetic and environmental factors underlying disease pathogenesis remains unclear.</p> Objectives <p>This study aimed to investigate the complex relationships between dietary components, nutrient profiles, and FMF symptoms, with a focus on developing personalized nutrition strategies for FMF management.</p> Methods <p>This cross-sectional study recruited 100 FMF patients and 50 healthy controls, matched for age, sex, and ethnicity. Participants completed a comprehensive food frequency questionnaire, and blood samples were analyzed for biomarkers of inflammation and nutrient profiles. Advanced statistical methods were employed to identify patterns and correlations between dietary components, nutrient profiles, and FMF symptoms.</p> Results <p>The study revealed significant correlations between FMF symptom severity and specific dietary components, including pro-inflammatory omega-6 fatty acids, advanced glycation end-products, and lectins, as well as anti-inflammatory omega-3 fatty acids, antioxidants, and fiber. Factor analysis identified four distinct dietary patterns, which collectively explained 92.86% of the variance in FMF symptom severity. The adoption of an anti-inflammatory diet was associated with improved symptom management and quality of life.</p> Conclusions <p>This study provides novel insights into the complex relationships between dietary components, nutrient profiles, and FMF symptoms, highlighting the potential for personalized nutrition strategies to revolutionize FMF management. The identification of specific dietary components associated with FMF symptom severity has significant implications for the development of targeted dietary recommendations that address individual patients’ unique requirements. Further research is necessary to fully elucidate the mechanisms underlying these relationships and to develop effective personalized nutrition strategies for FMF management.</p> WHO clinical trial registry <p>TCTR20241022008 (Familial Mediterranean Fever - Dietary Habits and Symptom Management, Date of Registration: 17 November, 2024) (<a href="https://www.thaiclinicaltrials.org/show/TCTR20241022008">https://www.thaiclinicaltrials.org/show/TCTR20241022008</a>).</p>