Are serum vitamin D, calcium and phosphorous associated with restless leg syndrome? A systematic review and meta-analysis

Abstract

Background: It is hypothesized that vitamin D deficiency, and calcium/phosphate imbalance could be involved in the pathophysiology of restless leg syndrome (RLS). This systematic review and meta-analysis of observational studies were carried out to reach a firm conclusion regarding the possible association between vitamin D, calcium and phosphorous levels with RLS in end-stage renal disease (ESRD) patients, other comorbidities and healthy population.

Methods: PubMed, Scopus, ISI Web of Science, and Cochrane's library were systematically searched up to June 2020. Quality assessment of the included observational studies was performed using Newcastle-Ottawa Quality Assessment Scale. Statistical analyses were done using STATA 11.2. A P-value <0.05 were considered statistically significant.

Results: A total of 36 studies involving 9590 participants were included in this systematic review and meta-analysis. We found that serum vitamin D level is significantly lower (WMD -3.39 ng/mL; 95% CI, -5.96 to -0.81; P = 0.010; I² = 86.2%) and phosphorous (SMD 0.19; 95% CI, 0.04-0.34; P = 0.011; I² = 83.6%) is significantly higher in RLS individuals compared to the non-RLS individuals. However, the mean difference of serum calcium was not significant in comparison between RLS and control groups (SMD -0.01; 95% CI, -0.19 to 0.18; P = 0.957; I² = 89.2%).

Conclusion: Results revealed a significant association between serum vitamin D and phosphorous with RLS. However, further prospective cohort studies and clinical trials are needed for better understanding of the relationship between these variables.

Keywords: Calcium; Meta-analysis; Phosphorous; Restless leg syndrome; Systematic review; Vitamin D.