Beyond the neurological horizon: A metabolic paradigm shift in intravenous iron therapy for restless legs syndrome

Intravenous (IV) iron therapy has substantially advanced the therapeutic landscape of Restless Legs Syndrome (RLS), offering potent disease-modifying benefits by directly addressing the central pathophysiology of brain iron deficiency. Consequently, ferric carboxymaltose (FCM) has rapidly emerged as the preferred formulation within sleep medicine, championed for its robust neurological efficacy and administration convenience. However, an interdisciplinary evaluation reveals a critical metabolic blind spot: FCM's unique propensity to induce intact fibroblast growth factor 23 (iFGF23)-mediated hypophosphatemia. While sleep specialists frequently dismiss this complication as a transient laboratory anomaly, extensive hematological evidence demonstrates that it precipitates severe, prolonged metabolic derangements, including osteomalacia, pathological fractures, and profound muscle weakness that clinically mimics RLS exacerbation. This perspective advocates for a paradigm shift in neuro-nutrition and sleep medicine, urging a targeted transition toward safer, equally efficacious alternatives, notably ferric derisomaltose (FDI), ferumoxytol, and low molecular weight iron dextran (LMW ID). By implementing a personalized, risk-stratified decision algorithm, clinicians can harmonize the neurological objectives of RLS treatment with the imperative of systemic metabolic safety.