Restless legs syndrome

Overview

Iron (5 studies) has the strongest evidence for restless legs syndrome, particularly when iron stores are low. Oral ferrous sulfate (commonly 325 mg twice daily with vitamin C) and intravenous iron may reduce symptoms, with effects comparable to some standard medications in trials.

Valerian (2 studies) has unclear benefit—one trial found no effect, another lacked a placebo control. Melatonin (1 study) did not improve symptoms and may worsen leg movements. See the heatmap and evidence reviews below.

Effect graph

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Relevant supplements

Relevant supplements sorted by DEX Score.


Iron	★★★★★	Medium
Valerian	★★★★★	Low
Melatonin	★★★★★	Very Low / None

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Studies

Find individual evidence reviews for supplements sorted by DEX Score.

3 supplements for , and rated at least stars. All purchase bands. No minimum star filter.

IronView supplement →

Consider purchase★★★★★

How we scored this

Effect SizeMediumEvidenceHighTrustVery High

Evidence Review

Restless legs syndrome (RLS), a condition causing uncomfortable leg sensations and an urge to move, is often linked to low iron levels.
Taking iron pills, usually ferrous sulfate 325 milligrams twice a day with vitamin C 100 milligrams twice a day for three months, can help reduce symptoms for many people.
This treatment might work as well as some medicines commonly used for RLS.
Iron can also be given through a vein.
Receiving two doses of intravenous iron carboxymaltose five days apart often helps improve symptoms and quality of life within a month, no matter your iron levels.
Another type of intravenous iron, iron sucrose, has been tested but there is not enough proof yet that it helps with RLS.
Some research shows that intravenous iron ferumoxytol works about as well as taking iron tablets daily for six weeks, but more studies are needed to confirm this.

Browse 5 studies1 meta-analysis

RCTA randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia2024n=70

In 70 RLS patients with iron-deficiency anemia, IV ferumoxytol and oral ferrous sulfate both markedly improved RLS symptoms over 6 weeks with no significant difference between routes and no serious adverse events.

Effect: Benefit
Duration: 6 weeks
Population: Restless legs syndrome patients
Participants: 70

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MetaIron supplementation for restless legs syndrome - A systematic review and meta-analysis2019

A meta-analysis of 10 RLS trials found iron therapy reduced IRLS scores by 3.55 points (oral or IV) versus control, supporting iron as effective RLS treatment despite increased non-severe adverse events.

Effect: Benefit
Population: Restless legs syndrome patients

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GuidePractice guideline summary: Treatment of restless legs syndrome in adults: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology2016

AAN guidelines recommend considering pramipexole, rotigotine, or gabapentin enacarbil for moderate-severe primary RLS; IV ferric carboxymaltose has moderate evidence, and ferrous sulfate plus vitamin C may help when ferritin ≤75 µg/L.

Effect: Benefit
Population: Adults

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RCTComparison of the efficacies of oral iron and pramipexole for the treatment of restless legs syndrome patients with low serum ferritin2014n=30

In 30 RLS patients with low-normal ferritin, oral iron and pramipexole for 12 weeks similarly reduced IRLS scores, with response rates of 46.7% in each group.

Effect: Benefit
Duration: 12 weeks
Population: Restless legs syndrome patients
Participants: 30

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RCTEfficacy of oral iron in patients with restless legs syndrome and a low-normal ferritin: A randomized, double-blind, placebo-controlled study2009

In a 12-week double-blind RCT, oral iron reduced IRLS scores more than placebo in RLS patients with low-normal ferritin (10.3 vs 1.1 point decrease; p=0.01) and raised ferritin.

Effect: Benefit
Duration: 12 weeks
Population: Restless legs syndrome patients

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ValerianView supplement →

Reconsider purchase★★★★★

How we scored this

Effect SizeLowEvidenceLowTrustMedium

Evidence Review

It's unclear if valerian helps with restless legs syndrome.
One small study found no benefit when people took valerian every day for 8 weeks, but the study might not have been large enough to see a difference.
Another small study saw some improvement with valerian taken at night, but it didn’t have a placebo to compare against, so the results aren’t very reliable.

Browse 2 studies

RCTComparison the effect of valerian and gabapentin on RLS and sleep quality in hemodialysis patients: A randomized clinical trial2023

A crossover trial in 40 hemodialysis patients found gabapentin lowered restless legs syndrome scores more than valerian over one month, though both treatments similarly improved sleep quality.

Effect: Benefit
Duration: 1 month
Population: Hemodialysis patients

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RCTDoes valerian improve sleepiness and symptom severity in people with restless legs syndrome?2009n=17

An 8-week triple-blind RCT of 37 RLS patients found valerian 800 mg/day improved RLS symptom severity and reduced daytime sleepiness in patients with Epworth scores ≥10.

Effect: Benefit
Duration: 8 weeks
Dose: 800 mg/day
Population: Patients with restless legs syndrome
Participants: 17
Ages: 36–65

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MelatoninView supplement →

Do not purchase★★★★★

How we scored this

Effect SizeVery Low / NoneEvidenceLowTrustLow

Evidence Review

One very small study showed that taking 3 mg of melatonin before bed did not improve restless legs syndrome (RLS) symptoms and might even make leg movements worse. The study was very small and did not compare to a control group. Some research suggests melatonin could affect brain chemicals linked to RLS symptoms, so it might not be helpful.
Melatonin is unlikely to help with RLS and may even worsen symptoms.

Browse 1 study

Effects of melatonin and bright light administration on motor and sensory symptoms of RLS2010

In 8 restless legs syndrome patients, melatonin worsened RLS symptoms while bright-light suppression of melatonin improved them, supporting a melatonin-linked mechanism.

Effect: No Benefit

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Evidence visualised

Same ratings as above, aggregated so you can see coverage and imbalance.

Purchase-guidance distribution

How many supplements fall in each purchase band

Effect-size distribution

How large the reported benefits tend to be

Study distribution across 3 supplements for restless legs syndrome (8 studies total).
Supplement	DEX	Studies	Meta-analyses	Share
Iron	★★★★★72%	5	1	63%
Valerian	★★★★★44%	2	0	25%
Melatonin	★★★★★28%	1	0	13%

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