IV iron therapy at doses of 1000 mg or more significantly reduces restless legs syndrome severity, review finds
Intravenous ferric carboxymaltose (FCM) at a cumulative dose of at least 1000 mg produces meaningful reductions in restless legs syndrome (RLS) symptom severity and improves quality of life in patients with moderate-to-severe disease or those intolerant to oral iron, according to a narrative review in Sleep and Breathing.
The review also identifies transferrin saturation (TSAT) as a more sensitive predictor of treatment response than serum ferritin alone, offering a practical biomarker for guiding iron therapy decisions.
Key points
Phan and colleagues from the University of Medicine and Pharmacy at Ho Chi Minh City and the Pasteur Institute synthesized 17 key publications from 2015 to 2025, covering RCTs, systematic reviews, and large observational studies on iron supplementation for RLS.
- IV FCM at total dose ≥ 1000 mg produced significant reductions in International Restless Legs Syndrome Study Group (IRLS) rating scale scores, particularly in patients with moderate-to-severe RLS or those who could not tolerate oral iron. Side effects were mild, including transient hypophosphatemia.
- TSAT ≤ 35% emerged as a more sensitive biomarker for predicting a favorable treatment response than serum ferritin alone, which can be falsely elevated in inflammatory states.
- Oral iron remains a viable first-line option for children and patients with mild symptoms, though its efficacy is limited by gastrointestinal absorption.
- Subgroup benefits were noted in pregnant women, dialysis patients, and older adults, populations in which iron deficiency is common and RLS prevalence is elevated.
Implications
Brain iron deficiency is a well-established driver of RLS pathophysiology. The review reframes iron therapy as a disease-modifying intervention rather than symptomatic management alone. The shift toward IV formulations at adequate doses, guided by TSAT rather than ferritin, could change clinical practice for the substantial subset of RLS patients who do not respond adequately to oral supplementation.
The authors emphasize a personalized, biomarker-guided approach: first-line oral iron for mild cases, escalation to IV FCM at ≥ 1000 mg for moderate-to-severe presentations, with TSAT as the primary monitoring tool.
Source
Phan DM, Lam MY, Trang MN. Iron therapy & restless legs syndrome: a narrative review. Sleep Breath. 2026;30(4):202. DOI: 10.1007/s11325-026-03738-4