Nine Natural Compounds for Restless Legs Syndrome

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Restless legs syndrome and its debilitating array of symptoms that impact your quality of life may be relieved by safe natural treatments.

Restless legs syndrome (RLS) is a neurological sensory movement disorder that causes people to move their legs at night, possibly resulting in poor sleep quality, depression, fatigue and pain. Chronic insomnia has a negative impact on quality of life, daytime functioning, job performance and tenure.[i]

Studies associate RLS with high blood pressure, cardiovascular diseases, cerebrovascular disorders and diabetes.[ii] Some lifestyle changes may lower RLS risk and benefit RLS symptoms, such as controlling weight, not smoking, exercising regularly[iii],[iv] and consuming only a moderate amount of alcohol.[v]

Presently, there is no cure for RLS, but symptoms are most often managed through pharmacological solutions, such as dopaminergic agents, anti-epilepsy drugs, opioids or benzodiazepines, which can become ineffective or cause severe side effects over time.[vi]

Researchers have found that deficiencies of iron and dopamine in the brain and low levels of folic acid (vitamin B9) and vitamins B12 and D were associated with RLS. Certain genes (nitric oxide) may be markers for diagnosing the disease and key to finding the best treatments.

The top nine natural substances to treat RLS include iron, folic acid, peony, vitamins B and D, L-arginine, D-ribose, olive oil massage and valerian.

1. Iron

Researchers found a strong relationship between body iron stores -- serum ferritin -- and the severity of RLS symptoms.[vii] Insufficient levels of brain iron cause a dopaminergic abnormality.[viii]

Clinical research of 68 RLS patients showed those who used 1,000 milligrams (mg) of ferric carboxymaltose significantly improved RLS symptoms compared to the non-iron placebo, and the effects lasted as long as six months.[ix],[x]

In a study of 324 pregnant women, RLS was more common in those with iron and folic acid deficiencies and deficits worsened in the third trimester.[xi]

In a systematic review of 10 studies including 428 total participants, the use of iron resulted in greater improvement in restless leg scores and compared favorably to the dopamine agent pramipexole without adverse effects.[xii]

Rats and mice fed diets causing an iron deficiency had downregulated adenosine A1 receptors in the brain cortex and striatum, which increased RLS symptoms of hyperarousal and periodic limb movements during sleep.[xiii]

RLS experts recommend that all RLS patients with serum ferritin levels of 75 micrograms per liter or less and transferrin saturation below 45% receive a trial of oral iron therapy -- 325 mg of ferrous sulfate in combination with 100 mg to 200 mg of vitamin C with each dose to enhance absorption once daily or once every second day taken at night.[xiv]

Intravenous administration of iron -- ferric carboxymaltose at 1,000-mg dose every five or seven days -- should be given if RLS symptoms persist after three months of oral treatment.[xv]

2. Folic Acid

In addition to iron therapies, researchers found that folic acid administration successfully alleviated the symptoms of RLS.[xvi] Supplementation with serum ferritin and serum folate during pregnancy is recommended to minimize the complaints of restless legs and promote more consolidated sleep and a better mood during pregnancy.[xvii]

In a study of six women aged 31 to 70 years, folic acid therapy improved RLS symptoms such as depression, muscular and intellectual fatigue, restless legs, poor sleep quality and muscular pain.[xviii]

3. Peony

In a meta-analysis of 12 studies comprising 639 RLS subjects, those given a peony (Paeonia Radix) herbal medicine increased their total effective rate, the restless legs syndrome rating scale and sleep quality scores as compared to the placebo.[xix]

Recent clinical trials have found that the traditional Chinese medicine Shaoyao Gancao Tang -- made of peony and Chinese licorice root -- combined with acupuncture was an effective and safe therapeutic agent for RLS.[xx]

4. Vitamin B

Vitamin B complex capsules -- fursulthiamine (50 mg), hydroxocobalamin (250 mg), pyridoxal phosphate (30 mg) and riboflavin (5 mg) -- were given in a study of 28 elderly patients with high blood pressure who had severe nocturnal leg cramps. B complex treatment significantly reduced the frequency, intensity and duration of nocturnal leg cramps.[xxi]

Vitamin B12 deficiency was independently associated with RLS in a study of 160 subjects comparing RLS and healthy patients. The lower the vitamin B12, the worse the restless leg symptoms and depression were.[xxii]

5. Vitamin D

In a study of 35 RLS patients, 21 (60%) had a vitamin D deficiency and received vitamin D therapy, which improved RLS symptom severity, impact on sleep, symptom measures and disease impact measures such as frequency and mood.[xxiii]

From a systematic review of 36 studies involving 9,590 participants, serum vitamin D levels were found to be significantly lower and phosphorus significantly higher in RLS individuals compared to the non-RLS individuals.[xxiv]

6. Arginine

Sixty percent of patients with RLS report a family history of the condition. In a gene study including 367 cases and controls, researchers found an association between variants in the neuronal nitric oxide synthase (NOS1) gene and RLS, and involvement of the nitric oxide (NO)/arginine pathway in the pathogenesis of RLS.[xxv]

Usage of NO-modulating agents such as L-arginine and iron therapy are currently gaining momentum as new treatment options as research confirms the involvement of genes and brain deficits in dopamine and iron in RLS pathology.[xxvi]

In a related study of pregnant women with preeclampsia -- symptoms of high blood pressure and high protein in the urine -- it’s revealed that levels of superoxide increase, and this reacts with NO, which may lead to a subsequent increase in blood pressure. Therefore, increasing the production of NO through L-arginine supplementation can overcome the oxidative effects of superoxide production and significantly reduce blood pressure.[xxvii]

Similarly, in an umbrella review of seven meta-analyses, L-arginine benefits included reduced systolic and diastolic blood pressure in adults with high blood pressure, reduced diastolic blood pressure in pregnant women with gestational high blood pressure and reduced length of time in the hospital for surgical patients.[xxviii] These two studies provide evidence for how L-arginine treatment may help in nitric oxide regulation and positively affect RLS symptoms.

7. D-Ribose

In a study of familial RLS, treatment with 15 grams (g) of D-ribose daily for nine weeks did not eliminate all discomfort of RLS, but the severity and onset of symptoms affecting quality of life were improved with D-ribose without any adverse reactions.[xxix]

Benefits reported with D-ribose treatment -- 15 g daily for 60 days -- included pain relief, replaced energy stores in cells after exercising and increased heart energy and function in heart disease patients.[xxx],[xxxi]

Forty-one patients with a diagnosis of fibromyalgia and chronic fatigue syndrome were given 15 g of D-ribose daily for 35 days and experienced a significant improvement in energy, sleep, mental clarity, pain intensity and well-being, as well as an improvement in patients’ global assessment.[xxxii] These related research studies show the potential of D-ribose in improving RLS symptoms.

8. Olive Oil Massage

Extra virgin olive oil has almost double the melatonin content of other refined oils and this could account for its benefits of inducing sleep and increasing sleep quality.[xxxiii]

In research of 60 patients with uremic restless legs syndrome -- a form of RLS due to advanced kidney diseases -- those massaged with 10 milliliters of olive oil per leg for five minutes on each leg twice a week for three weeks had highly reduced uremic RLS symptom severity compared to the liquid paraffin placebo group.[xxxiv]

In a meta-analysis of five studies including 369 participants, massage alone was effective against RLS symptoms and massage with lavender oil also reduced symptom severity and improved symptoms in sleep disorders. More research with larger sample sizes and in-depth comparisons is warranted but massage with olive oil should be considered a safe and viable alternative for those with RLS.[xxxv]

9. Valerian

In a sample of 37 RLS participants aged 36 to 65 years, those who received 800 mg of valerian for eight weeks improved their RLS symptoms and decreased any daytime sleepiness reported compared to the placebo.[xxxvi]

A systematic review of 16 valerian studies examining a total of 1,093 patients revealed a statistically significant benefit of improved sleep without negative side effects.[xxxvii]

Valerian taken at 600 mg showed a comparable efficacy to 10 mg of the benzodiazepine oxazepam but was safer as an insomnia therapy.[xxxviii]

Natural Alternative RLS Treatments

Although today many doctors rely heavily on drug-based solutions to treat RLS, the use of natural compounds that are safer and longer lasting may positively impact RLS.

Some of the most effective natural remedies are iron, folic acid, peony, vitamin B12 or B complex, vitamin D, arginine, D-ribose, olive oil massage and valerian.

To delve more into the research, see’s evidence-based studies on Restless Leg Syndrome.


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