Iron supplementation for restless legs syndrome
In line with the American Academy of Sleep Medicine (AASM) guidelines, all patients with suspected or diagnosed Restless Legs Syndrome (RLS) should typically be tested for ferritin levels (iron stores) and total iron-binding capacity with calculated percentage transferrin saturation (TSAT). Patients should discontinue any oral iron formulations 48-hours before obtaining serum iron measurements because oral iron supplements affect plasma hepcidin levels and iron absorption for that time. Even if a person is not clinically anemic, low to normal iron levels can trigger RLS symptoms in the brain. If your ferritin is below 75µg/L, or TSAT <45% iron supplementation (oral or IV) may resolve the RLS symptoms without the need for lifelong medication.
Oral iron dosing
Oral iron is poorly absorbed from the gastrointestinal (GI) system. As serum ferritin levels increase absorption decreases with minimal absorption once serum ferritin concentration is ≥ 75 μg/l. Absorption also decreases after each dose of oral iron for about 48-hours. Therefore, oral iron should be administered no more frequently than once a day and preferably once every other day. Oral Iron is often prescribed with Vitamin C (100 mg–200 mg) to increase absorption.
Figure 1: Iron tablets
Evidence from non-human primates indicates that iron is preferentially transported into the brain at night. Therefore, a nighttime dose of iron is considered potentially more effective than a morning dose. However if Magnesium (Mg) is also being taken as a supplement for RLS then it it is best ideally, to take the Mg at night and the iron in the morning as Mg and Iron interact with each other. Iron should be taken at least two hours after ingesting calcium, magnesium, or caffeine. Gastrointestinal side effects to iron are common, and should they develop, iron can be taken with food. A common oral iron regime is 325mg ferrous sulfate (65mg elemental iron).
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Oral iron therapy side effects
Iron supplements, particularly oral iron supplements frequently cause gastrointestinal side effects. These side effects are often dose-dependent.
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Constipation: One of the most frequent complaints.
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Nausea and Upset Stomach: Often minimized if taken with food (though food can reduce iron absorption).
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Abdominal Pain or Cramping: Mild to moderate discomfort in the upper or lower abdomen.
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Diarrhea: Less common than constipation, but can occur.
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Dark or Black Stools: A completely harmless, expected byproduct of unabsorbed iron passing through the digestive tract.
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​Intravenous (IV) iron
In patients with ferritin concentration in the normal serum range, intravenous (IV) iron infusions are successful in improving RLS in 37% to 59% of patients. In line with the 2026 "An Updated Algorithm for the Management of Restless Legs Syndrome" published in the Mayo Clinic proceedings IV iron is warranted when there is; chronic persistent RLS with TSAT < 45% and serum ferritin concentration in the range of 75μg/l to 300μg/l (oral iron is not readily absorbed in this range). Else IV iron can be administered if the serum ferritin concentration is <75μg/l and one or more of the following circumstances apply:
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An inability to absorb oral iron due to GI disease or prior bariatric surgery
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Ferritin levels remain low (<75µg/L) 3-months after initiation of oral iron therapy
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An inability to tolerate oral iron due to side effects
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RLS has not improved after 3-months of oral iron therapy
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A quick response to treatment is warranted ​
It should be noted that IV should not be given if the TSAT is >45% to avoid the possibility of hepatic iron overload.
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The clinical response to IV iron treatment is not always immediate and may be delayed for up to 6 to 8-weeks. In patients with severe RLS causing considerable distress and sleeplessness, a joint decision should be made between the patient and the healthcare provider whether to introduce or modify pharmacologic therapy in parallel to the administration of intravenous iron rather than waiting to determine if iron therapy alone alleviates the symptoms.​​​​
Figure 2: Woman receiving an IV iron infusion
If initial infusions of IV iron have been successful in relieving RLS symptoms, repeat infusions can be considered if RLS recurs greater than 3-months after the initial treatment. Repeat iron studies must demonstrate serum ferritin concentration ≤300 μg/l and TSAT <45%.
Serum iron levels should be rechecked after 3-months of any iron therapy.​​
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Do not begin, stop or change an iron supplement without advice from your doctor or pharmacist.
​Last reviewed: 07/09/2026