What is the best iron supplement for Restless Legs Syndrome (RLS)?

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Last updated: April 17, 2025View editorial policy

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From the Guidelines

Ferrous sulfate is the best iron supplement option for restless leg syndrome (RLS) associated with iron deficiency, as suggested by the American Academy of Sleep Medicine 1.

Key Considerations

  • A typical regimen involves taking 325 mg of ferrous sulfate (containing 65 mg of elemental iron) once or twice daily, preferably on an empty stomach with vitamin C (such as orange juice) to enhance absorption.
  • Treatment should continue until serum ferritin levels reach at least 50-75 ng/mL, which may take several months.
  • Other formulations like ferrous gluconate or ferrous fumarate are alternatives if sulfate causes digestive issues, though they contain less elemental iron.
  • Iron supplementation works for RLS by addressing the underlying iron deficiency that affects dopamine production in the brain, as iron is a cofactor for tyrosine hydroxylase, the enzyme that produces dopamine.

Important Precautions

  • Before starting supplements, get your serum ferritin and iron saturation levels checked, as iron therapy is most effective for RLS patients with ferritin levels below 75 ng/mL.
  • Monitor for side effects like constipation, nausea, or dark stools, and avoid taking iron with calcium, dairy, coffee, tea, or certain medications that can reduce absorption.

Additional Recommendations

  • The American Academy of Sleep Medicine also suggests the use of IV iron sucrose over no IV iron sucrose in patients with ferritin < 200 ng/mL and transferrin saturation < 20% 1.
  • However, ferrous sulfate remains the preferred oral iron supplement option due to its efficacy and safety profile 1.

From the Research

Iron Supplements for Restless Legs Syndrome

  • The effectiveness of iron supplements in treating restless legs syndrome (RLS) has been studied in several trials 2, 3, 4, 5, 6.
  • A 2012 study found that iron therapy did not result in significantly more side effects than placebo, but the evidence was insufficient to determine whether iron therapy is beneficial for the treatment of RLS 2.
  • A 2019 study found that intravenous iron was more efficacious than placebo in treating RLS, with a significant decrease in the International Restless Legs Syndrome score (IRLSS) 3.
  • Another 2019 study found that iron supplementation was associated with a significant decrease in the IRLSS score and an increase in the percentage of patients with improvement of the IRLSS score 6.
  • A 2024 study found that both intravenous and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups 4.
  • A 2019 systematic review and meta-analysis found that iron therapy probably improves restlessness and RLS severity in comparison to placebo, and may not increase the risk of side effects in comparison to placebo 5.

Types of Iron Supplements

  • Intravenous iron, including ferric carboxymaltose (FCM) and iron sucrose, has been found to be effective in treating RLS 3, 6.
  • Oral iron, including ferrous sulfate, has also been found to be effective in treating RLS 4, 6.
  • The optimal formulation and dosage of iron supplements for RLS are not yet clear and require further study 5.

Safety and Tolerability

  • Iron supplements have been found to be generally safe and well-tolerated in patients with RLS 2, 3, 4, 5, 6.
  • The risk of adverse events associated with iron supplements is low, and most adverse events are mild and not severe 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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