What are the target iron levels for an adult with Restless Leg Syndrome (RLS)?

Iron Parameter Goals for Adults with Restless Legs Syndrome

For adults with RLS, the American Academy of Sleep Medicine recommends iron supplementation when serum ferritin is ≤75 ng/mL or transferrin saturation is <20%—thresholds substantially higher than general population iron deficiency cutoffs. 1, 2

RLS-Specific Iron Thresholds

Adults with RLS

• Ferritin ≤75 ng/mL OR transferrin saturation <20%: Iron supplementation is recommended, using either oral ferrous sulfate or IV iron formulations 1, 2, 3
• Ferritin 75-100 ng/mL: Use IV iron formulations ONLY (oral iron is poorly absorbed in this range and ineffective) 1, 3
• Ferritin >100 ng/mL: Iron supplementation is generally not indicated based on current evidence 1

Children with RLS

• Ferritin <50 ng/mL: Iron supplementation is recommended 1, 2

Special Population: End-Stage Renal Disease (ESRD)

• Ferritin <200 ng/mL AND transferrin saturation <20%: IV iron sucrose is conditionally recommended 4, 2

Critical Testing Requirements

All patients with clinically significant RLS must have serum ferritin and transferrin saturation checked before initiating treatment. 1, 2, 3

Proper Testing Protocol

• Draw blood in the morning (fasting preferred) 1, 2, 3
• Patient must avoid iron-containing supplements and foods for at least 24 hours before testing 1, 2, 3
• Recheck iron parameters once or twice yearly during ongoing iron therapy 5

Why RLS Requires Higher Iron Thresholds

Brain iron deficiency plays a central role in RLS pathophysiology, even when serum iron appears normal by general population standards. 1, 6

• General population iron deficiency is typically defined as ferritin <15-30 ng/mL, but this threshold is inadequate for RLS 1
• RLS patients require higher ferritin levels (≥50-75 ng/mL) for optimal neurological function and CNS iron availability 1, 6
• The higher thresholds reflect the specific need for H-ferritin binding and macrophage iron uptake necessary for CNS penetration 1

Treatment Algorithm Based on Iron Status

Ferritin ≤75 ng/mL or Transferrin Saturation <20%

• First-line option: Oral ferrous sulfate (65 mg elemental iron daily) - conditional recommendation with moderate certainty 1, 2, 6
• Alternative first-line: IV ferric carboxymaltose (1000 mg) - strong recommendation with moderate certainty 1, 2, 6
• IV ferric carboxymaltose may be preferred for faster response and when oral iron is not tolerated 6, 7

Ferritin 75-100 ng/mL

• Use IV iron formulations exclusively (oral iron poorly absorbed and ineffective in this range) 1, 3
• IV ferric carboxymaltose (1000 mg) is the preferred formulation 1, 6

Ferritin >100 ng/mL

• Iron supplementation is not indicated 1
• Focus on other RLS treatments (alpha-2-delta ligands as first-line pharmacotherapy) 2, 3

Common Pitfalls to Avoid

• Do NOT use general population ferritin cutoffs (<15-30 ng/mL) for RLS management—this misses the majority of RLS patients who would benefit from iron therapy 1
• Do NOT assume all IV iron formulations are equivalent—iron sucrose lacks efficacy except in dialysis patients; use ferric carboxymaltose, ferumoxytol, or low molecular weight iron dextran instead 1
• Do NOT test iron studies while patients are taking supplements—wait at least 24 hours after the last iron-containing product 1, 2
• Do NOT forget to screen for hemochromatosis before initiating iron therapy—measure transferrin saturation and ferritin to exclude iron overload states 5
• Do NOT use oral iron for ferritin 75-100 ng/mL—it will be ineffective due to poor absorption in this range 1

Monitoring During Iron Therapy

• Recheck serum ferritin and transferrin saturation once or twice yearly during ongoing iron supplementation 5
• Monitor for signs of iron overload, particularly in patients with elevated baseline transferrin saturation 5
• Patients with a history suggestive of hemochromatosis or elevated pre-treatment iron parameters should undergo evaluation before iron therapy 5