Magnesium's Role in Restless Legs Syndrome
Magnesium is not recommended as a standard treatment for RLS based on current evidence-based guidelines, though it may be considered as adjunctive therapy after addressing iron deficiency and implementing first-line treatments with alpha-2-delta ligands. 1, 2
Current Guideline Position
The 2025 American Academy of Sleep Medicine clinical practice guideline does not include magnesium among its recommended treatments for RLS. 1 The guideline prioritizes an evidence-based algorithm that starts with assessing and correcting iron status (ferritin ≤75 ng/mL or transferrin saturation <20%), followed by first-line pharmacological treatment with gabapentin, gabapentin enacarbil, or pregabalin. 2
Research Evidence on Magnesium
Despite the absence of guideline recommendations, research studies show mixed but potentially promising results:
A 2024 open-label pilot study demonstrated that magnesium citrate 200 mg daily for 8 weeks significantly reduced RLS symptom severity scores and improved quality of life, with notable improvements in periodic limb movements during wakefulness. 3 This represents the most recent evidence, though the open-label design limits its strength.
A 2022 randomized controlled trial found that 250 mg magnesium oxide daily for 2 months significantly reduced disease severity and improved sleep quality compared to placebo. 4
A 1998 pilot study showed that magnesium 12.4 mmol in the evening reduced periodic limb movements associated with arousals and improved sleep efficiency. 5
However, a 2019 systematic review concluded that the evidence was insufficient to determine whether magnesium effectively relieves RLS or PLMD, noting that the single randomized placebo-controlled trial may have been underpowered. 6
Proposed Mechanism
While not definitively established, magnesium may work through modulation of neuromuscular excitability and potentially through interactions with the dopamine-iron pathophysiology that underlies RLS. 5 The core pathophysiology involves impaired dopamine transport in the substantia nigra due to reduced intracellular iron. 7
Clinical Application Algorithm
Step 1: Address iron deficiency first
- Check morning fasting ferritin and transferrin saturation 2
- Supplement with oral ferrous sulfate if ferritin ≤75 ng/mL or transferrin saturation <20% 2
Step 2: Initiate first-line pharmacotherapy
- Start gabapentin, gabapentin enacarbil, or pregabalin as strongly recommended by the American Academy of Sleep Medicine 1, 2
Step 3: Consider magnesium as adjunctive therapy
- If symptoms persist despite iron repletion and first-line treatment, magnesium citrate 200 mg daily or magnesium oxide 250 mg daily may be added 2, 3
- This approach is supported by recent research but not by formal guidelines 4, 3
Critical Pitfalls to Avoid
Never use magnesium as monotherapy for clinically significant RLS without first addressing iron status and considering guideline-recommended treatments. 2 Insomnia is present in roughly 90% of people with RLS and represents the primary morbidity, requiring evidence-based interventions. 2
Do not delay effective treatment by trialing magnesium first, as alpha-2-delta ligands have strong evidence (moderate certainty) for efficacy and avoid the augmentation phenomenon seen with dopamine agonists. 1, 2
Recognize that normal serum magnesium levels do not exclude potential benefit, as the 2024 study showed symptom improvement without changes in serum magnesium levels. 3
Bottom Line
While emerging research suggests magnesium supplementation may provide symptomatic benefit in RLS, particularly for sleep quality and periodic limb movements, it should be positioned as an adjunctive or alternative therapy rather than first-line treatment. The evidence base remains limited compared to alpha-2-delta ligands and iron therapy, which have stronger guideline support and more robust clinical trial data. 1, 2, 6