Ferritin Goal for Restless Leg Syndrome
The target serum ferritin level for managing RLS is ≤75 ng/mL or transferrin saturation <20% to initiate iron supplementation, with an optimal goal of achieving ferritin levels above 75-100 ng/mL for symptom control. 1, 2
Iron Status Assessment
- Check serum ferritin and transferrin saturation in all patients with clinically significant RLS, ideally in the morning after avoiding iron-containing supplements and foods for at least 24 hours prior to blood draw 1, 2
- RLS requires higher ferritin thresholds than the general population because brain iron deficiency plays a key role in pathophysiology, even when serum iron appears normal 2, 3
- CSF studies demonstrate that patients with RLS have significantly lower CSF ferritin (1.11 ng/mL versus 3.50 ng/mL in controls) despite normal serum ferritin, confirming central nervous system iron deficiency 3
Treatment Algorithm Based on Ferritin Levels
For ferritin ≤75 ng/mL or transferrin saturation <20%:
- Initiate oral iron (ferrous sulfate 65 mg elemental iron) or IV ferric carboxymaltose (1000 mg) as first-line treatment 1, 4
- Oral iron is conditionally recommended with moderate certainty of evidence 1, 2
- IV ferric carboxymaltose is strongly recommended with moderate certainty of evidence 1, 2
For ferritin 75-100 ng/mL:
- Use IV iron formulations only (not oral iron) 1, 4
- Oral iron absorption is poor in this range and will have minimal effect on RLS improvement 4, 5
- IV iron can improve RLS symptoms even at ferritin levels between 75-100 ng/mL 5
For ferritin >100 ng/mL:
- Iron supplementation is generally not indicated based on current evidence 4
Pediatric Considerations
- In children with RLS, initiate iron supplementation if serum ferritin <50 ng/mL with oral or IV formulations 1, 2
Critical Pitfalls to Avoid
- Do not use general population ferritin cutoffs (<15-30 ng/mL) for RLS management, as these are far too low for neurological function 4
- Be aware that ferritin assays differ significantly between manufacturers (Beckman versus Roche methods can vary by 60% at the 75 ng/mL threshold), so use transferrin saturation as an additional parameter 6
- The Roche method yields approximately 60% higher values than Beckman at the 75 ng/mL cutoff (121 ng/mL Roche equivalent), requiring adjustment of treatment thresholds based on your laboratory's assay 6
- Do not test iron studies while patients are taking supplements; wait at least 24 hours after the last iron-containing product 1, 4
Evidence for Higher Ferritin Targets
- A randomized controlled trial demonstrated that ferric carboxymaltose (1000 mg IV) significantly improved RLS severity scores by week 12 in patients with ferritin <75 μg/L or ferritin 75-300 μg/L with transferrin saturation <20% 7
- Oral iron therapy in patients with low-normal ferritin (mean 40.6 ng/mL) showed statistically significant improvement in RLS symptoms after 12 weeks compared to placebo 8
- These guidelines differ substantially from general population iron supplementation recommendations because RLS pathophysiology involves central dopaminergic dysfunction related to brain iron deficiency 1, 3