Role of vitamins in the pathogenesis and treatment of restless leg syndrome: A systematic review and meta-analysis

Abstract

We performed a meta-analysis to assess the role of vitamins in the possible pathogenesis and treatment of RLS (Restless Leg Syndrome). A systematic search of the PubMed, Cochrane, Embase, and Web of Science databases was conducted. Fifty-nine studies on the relationship between vitamins and RLS were included, as well as four randomized controlled trials (RCTs) on vitamin treatment of RLS. Compared with non-RLS patients, serum vitamin D levels were significantly lower both in primary (P = 0.009) and secondary (P = 0.003) RLS patients, and appeared to be positively correlated with disease severity. Serum folate levels were lower in pregnant RLS patients than in pregnant non-RLS patients (P = 0.007), but this phenomenon was not seen in non-pregnant RLS patients (P = 0.65). Vitamin B12 (P = 0.59) and B1 (P = 0.362) deficiencies were not found in RLS patients. Oral vitamin B6 significantly improved primary RLS (P < 0.0001), while vitamin D did not (P = 0.05). Oral vitamin C (P < 0.00001), E (P < 0.0001), and vitamin C + E (P < 0.00001) all significantly improved hemodialysis-associated RLS with equal efficacy. Vitamin C is equivalent to 0.18 mg of pramipexole for the treatment of RLS (P = 0.81). In this meta-analysis, low vitamin D levels were found in patients with RLS, low folate levels were associated with RLS only in pregnant women, and vitamin C/E/B6 may improved symptoms in patients with RLS. These results suggest that vitamin deficiency or insufficiency may be related to the pathogenesis of RLS.

Fig 1. Flowchart of study selection.

Fig 2. a. RLS patients had significantly lower levels of serum vitamin D than controls

; b. The rate of serum vitamin D deficiency/insufficient in RLS patients was significantly higher than that in controls; c. Patients with severe RLS had lower vitamin D levels than those with mild-moderate RLS; d. RLS patients with deficient vitamin D levels had significantly higher IRLSSG scores than those with normal vitamin D levels; e. Participants with vitamin D deficiency had a higher proportion of RLS detected than participants with normal vitamin D levels; f. Dialysis patients with RLS had significantly lower levels of serum vitamin D than those without RLS.

Fig 3. a. Serum folate levels were significantly lower in pregnancy woman with RLS than those without RLS, while folate levels in non-pregnant RLS patients were not significantly different from controls

; b. The rate of folate deficiency in pregnant or non-pregnant RLS patients was not different from that in the non-RLS controls; c. No statistical difference in serum vitamin B12 levels between patients with primary/secondary RLS and controls; d. No difference in the incidence of vitamin B12 deficiency between RLS patients and controls.