Folic Acid - Reports exist of folic acid reducing symptoms associated with restless leg syndrome (RLS) such as numbness, cramps, and paresthesias (1). Pregnant women have a two to three times increased risk of developing RLS possibly due to deficiency of folic acid and iron (2). One study showed that reduced serum folic acid levels were correlated with restless legs syndrome in pregnancy and supplementation could minimize these symptoms and promote better sleep (3).

Vitamin B12 - A study of nearly 800 seniors showed that vitamin B12 deficiency is common in subjects with neurosensory deficits and RLS (4). There are some preliminary clinical reports that the cyanocobalamin form of vitamin B12 can help relieve tremor associated with restless leg syndrome (5).

Iron - Low levels of iron are associated with RLS in elderly populations, but occasionally plasma levels may not reflect a deficiency while bone marrow measurements can (6,7). A clinical study showed that treatment with iron supplements for 2 months significantly improved the RLS severity score (7). Research suggests abnormal brain iron metabolism plays a role in dopaminergic systems in the brain, influencing the circadian pattern of RLS, and interfering with sleep (8-10).

Magnesium and Calcium - Supplementation with magnesium may be useful for treating restless legs syndrome. In some RLS patients, magnesium treatment may decrease the amount of movement and increase the amount of sleep in mild to moderate cases (11). Magnesium deficiency in patients with RLS demonstrates changes in the EEG patterns observed in sleep such as decreased duration and percentage of restorative REM sleep (12). Calcium, an essential mineral, is required for optimal absorption and effectiveness of magnesium and contributes to normalized brain and neurological function. Typically, these two should be supplemented together in a 2:1 ratio.

Valerian - Valerian root is commonly used for sleeping disorders (RLS is classified as a sleep disorder) due to its sedative-hypnotic and anxiolytic effects. A double-blind, placebo controlled study of patients who took a combination of valerian and lemon balm demonstrated amelioration of negative effects of induced stress (13). A randomized, placebo controlled trial conducted at multiple centers showed that a combination of valerian and hops has moderate hypnotic effects, improving sleep and quality of life safely without causing rebound of sleep problems with discontinuation of treatment (14).

Lemon balm (Melissa officinalis) - Animal research provides evidence that lemon balm produces peripheral pain relief and can act as a sedative-hypnotic agent (15). Combined with valerian, lemon balm can improve the quality and quantity of sleep (16). As well, EEG research on a lozenge containing lemon balm demonstrated anxiolytic effects suggesting it could better help cope with emotional and physiological stress (17).

GABA (Gamma Amino Butyric Acid) - GABA is the primary inhibitory neurotransmitter in the central nervous system. Gapapentin, a structural analogue of GABA, is a conventional drug that in clinical trials has shown effectiveness in reducing sensory and motor symptoms of RLS and improving sleep related difficulties (18,19).

Glycine - Research is showing that glycine acts as a neurotransmitter and plays a central role in regulating motor reflexes and nociceptive pathways (20). The anticonvulsant drug diazepam exerts its effects through interaction with GABA and glycine receptors, and addition of glycine results in increased anticonvulsant effects in animals (21).

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