Is Iron Therapy an Effective Treatment for Restless Legs Syndrome?

The aim of the review was to assess the safety and efficacy of oral and parenteral iron for the treatment of RLS.

For patients with restless legs syndrome (RLS), iron therapy may improve both restlessness as well as disease severity when compared to placebo, according to the results of a recently published study.

The aim of the review was to assess the safety and efficacy of oral and parenteral iron for the treatment of RLS. The study authors searched for controlled trials published in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycNFO, and CINAHL between January 1995 and September 2017. The primary endpoint of the study was restlessness or sensations that were unpleasant, which were subjectively reported by the patient.

The study authors identified 10 studies with a total of 428 patients which were followed anywhere between 2 and 16 weeks. The International Restless Legs Scale (IRLS; range: 0–40) was used to quantify the primary outcome in 8 of the trials while the ninth trial utilized a different RLS symptom scale. In 9 of the studies analyzed, iron therapy was compared to placebo while one study compared it to the dopamine agonist pramipexole. 

“Combining data from the 7 trials using the IRLS to compare iron and placebo, use of iron resulted in greater improvement in IRLS scores (MD ‐3.78, 95% CI ‐6.25 to ‐1.31; I2= 66%, 7 studies, 345 participants) measured 2 to 12 weeks after treatment,” the study authors reported. They added, “Including an eighth study, which measured restlessness using a different scale, use of iron remained beneficial compared to placebo (SMD -0.74, 95% CI ‐1.26 to ‐0.23; I2 = 80%, 8 studies, 370 participants).” The certainty for this outcome was reported as moderate, according to the GRADE assessment. Additionally, a similar reduction in RLS severity was observed in the single study analyzing patients receiving iron therapy compared to those receiving pramipexole (MD: ‐0.40; 95% CI: ‐5.93, 5.13; N=30).

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Results of the study also showed that iron therapy did not significantly increase the risk of adverse events compared with placebo (risk ratio [RR]: 1.48; 95% CI: 0.97, 2.25; I2=45%; N=298). In addition, 1 study found patients who received iron therapy reported experiencing fewer adverse events compared to those who received pramipexole.

“Overall, the studies showed that iron is better than a placebo for reducing the severity of restless legs syndrome symptoms, although the benefit was low to moderate,” the authors concluded, adding that “Iron was helpful even if blood iron levels were normal at the start of the study.” More studies are needed, however, to determine which RLS patients would benefit the most, the type of iron to use and for what treatment duration.


Trotti  LM, Becker  LA. Iron for the treatment of restless legs syndrome. Cochrane Database of Systematic Reviews 2019, Issue 1. Art. No.: CD007834. DOI: 10.1002/14651858.CD007834.pub3.

This article originally appeared on MPR