Is “normal” ferritin truly enough? Strong correlation between iron stores and RLS severity in patients with normal ferritin levels

Objective We aimed to investigate the relationship between peripheral iron stores and symptom severity in drug-naive patients with idiopathic Restless Legs Syndrome (RLS) whose serum ferritin levels were within the laboratory reference range. Additionally, we sought to determine the independent effects of age, sex, comorbidities, and biochemical parameters in predicting RLS severity. Materials and methods This cross-sectional study was conducted at the neurology outpatient clinic of a single university hospital. A total of 113 drug-naive patients with idiopathic RLS were prospectively enrolled during clinical visits. Patients with ferritin levels outside the laboratory reference range (22–322 μg/L) or with major confounding comorbidities (e.g., peripheral neuropathy, renal failure, pregnancy) were excluded to ensure sample homogeneity Demographic data and comorbidities were recorded through face-to-face interviews. Disease severity was assessed by a neurologist using the International Restless Legs Syndrome Rating Scale. Ferritin, magnesium, vitamin B12, vitamin D, folate; and hemoglobin were analyzed in fasting venous blood samples. Multiple linear regression analysis was used to identify independent predictors of symptom severity. Results The mean age of the participants was 52 ± 13.8 years, and their median ferritin level was 51.4 μg/L. Multiple regression analysis identified serum ferritin level (p < 0.001) and age (p = 0.001) as independent and significant predictors of RLS severity. No independent effects of sex, hemoglobin, vitamin D, or other comorbidities on severity were detected. Conclusion Even when serum ferritin levels are within the so-called “normal” limits, a very strong negative correlation exists between ferritin level and symptom severity. Our findings highlight the importance of evaluating ferritin not merely as a threshold value in RLS management but as a continuous parameter that can be associated with symptom severity even within normal ranges. © 2026 Elsevier B.V.