Restless legs syndrome (RLS) is a common neurological sensorimotor disorder [1], mainly characterized by a strong desire to move both lower extremities, with symptoms appearing at rest, worsening at night, and decreasing after activity [2]. The prevalence of RLS in the general population varies by ethnicity, with a prevalence of up to 10 % in people of European descent and a relatively low prevalence of RLS in Asian populations [3], [4], [5], [6]. Previous large genome wide association studies (GWAS) have revealed the association of single nucleotide polymorphisms (SNPs) in RLS-associated risk genes with the development of RLS in humans, but the genetic basis and underlying pathophysiology remain unclear [7], [8]. The specific pathogenesis of RLS is not yet fully understood, but generally accepted views include brain iron deficiency, dopaminergic dysfunction, genetic variants, and abnormalities in the neural circuitry [3].

There is strong evidence supporting an association between vitamin B12 deficiency and neurodegenerative diseases [9]. Vitamin B12 plays a vital role in normal functioning of the nervous system [10]. In addition, vitamin B12 affects the metabolic pathway of homocysteine, resulting in the high levels of homocysteine, which damage neurons and is closely associated with neurodegenerative diseases [11]. However, few studies have focused on such associations in RLS. Therefore, there is an urgent demand on evaluating the associations between vitamin B12 level and RLS. Additionally, previous studies have also found that RLS patients have an increased prevalence of psychiatric disorder [12]. After supplementation of vitamin B12, the association with depressive disorders was substantially reduced [13]. Besides, increasing evidences have indicated that the common mechanisms linking depression and RLS [14]. So far, there are no data available on the relationship between vitamin B12 deficiency and either depression or anxiety in RLS patients.

The causal relationship between vitamin B12 deficiency and RLS remains unknown mainly due to the small number of studies, contradictory results, and the lack of large randomized clinical trials that evaluate the beneficial effects of vitamin B12 supplementation in RLS. Considering all these factors, the aim of our study was to assess the correlation of the serum vitamin B12 level with the severity of RLS symptoms, sleep quality, anxiety, and depression in patients with primary RLS. In addition, to determine if vitamin B12 levels are independently associated with the development of RLS.