From the Guidelines
Iron deficiency should be treated with oral iron supplements, typically ferrous sulfate 325 mg taken once or twice daily between meals with vitamin C to enhance absorption, as recommended by the American Academy of Sleep Medicine 1. For restless leg syndrome (RLS) associated with iron deficiency, iron replacement is the primary treatment, aiming for a serum ferritin level above 75 ng/mL. Some key points to consider in the treatment of RLS include:
- The use of ferrous sulfate over no ferrous sulfate in patients with appropriate iron status is suggested by the AASM 1.
- The AASM also suggests against the standard use of certain medications, such as levodopa, pramipexole, and ropinirole, due to the risk of augmentation and other adverse effects 1.
- In adults with RLS and end-stage renal disease (ESRD), the AASM suggests the use of IV iron sucrose over no IV iron sucrose in patients with ferritin < 200 ng/mL and transferrin saturation < 20% 1.
- Lifestyle modifications, such as maintaining regular sleep patterns, moderate exercise, avoiding caffeine and alcohol in the evening, and using relaxation techniques before bedtime, can also help manage symptoms. It's worth noting that the treatment of iron deficiency and RLS should be individualized and based on the patient's specific needs and circumstances, as recommended by the American Academy of Sleep Medicine 1. The most recent and highest quality study, published in 2025, provides the strongest evidence for the treatment of iron deficiency and RLS 1.
From the Research
Treatment of Iron Deficiency and Restless Leg Syndrome
- Restless legs syndrome (RLS) is a common neurologic syndrome that may be primary (idiopathic) or secondary to pregnancy, iron deficiency, or chronic renal insufficiency 2.
- Iron deficiency is a common cause of RLS, and iron replacement therapy is often used as a first-line treatment for patients with reduced body iron stores 2, 3.
- Studies have shown that iron supplementation can improve symptoms of RLS, with a significant decrease in the International Restless Legs Syndrome score (IRLSS) and an increase in the percentage of patients with improvement of the IRLSS score 3.
- However, not all studies have found a clear benefit of iron therapy for RLS, and the quality of trials has been variable 4, 5.
- Iron therapy may be more effective for patients with iron deficiency, and some studies have suggested that iron supplementation can improve quality of life and reduce symptoms of RLS in these patients 2, 6.
Iron Supplementation for RLS
- Iron supplementation can be administered orally or intravenously, and both forms have been shown to be effective in improving symptoms of RLS 3, 4.
- The optimal dose and duration of iron supplementation for RLS are not well established, and further research is needed to determine the best treatment regimen 3, 4.
- Iron supplementation is generally well tolerated, but it can cause adverse events such as gastrointestinal side effects and allergic reactions 3, 5.
Role of Iron in RLS Pathophysiology
- Iron plays a central role in the etiology of RLS, as it is a cofactor in dopamine production and patients with RLS have lower levels of dopamine in the substantia nigra 6.
- Iron deficiency may contribute to the development of RLS by reducing dopamine production and altering the circadian fluctuation of dopamine in the substantia nigra 6.
- Further research is needed to understand the pathophysiology of RLS and the role of iron in the development and treatment of the disorder 2, 6.