Vitamin D and Restless Legs Syndrome: A Review of Current Literature
Overview
Affiliations
This review presents a detailed summary of the current literature regarding RLS and vitamin D deficiency. To our knowledge it is the first review of its kind. We review the prevalence of vitamin D deficiency in RLS as well as the evidence for the use of vitamin D supplementation in RLS management. We further examine the literature for proteomic and genetic evidence of a role for vitamin D in the pathogenesis of RLS. An alteration in vitamin D binding protein in RLS is one of the most consistent findings in the proteomic studies. Furthermore, we examine the interaction of vitamin D with calcium, phosphorus, and parathyroid hormone and the possible role of these connections in RLS. We also explore the possible nexus between RLS and vitamin D in renal disease, cardiovascular and cerebrovascular disease as well as inflammation. In addition, we review the potential interaction between vitamin D and RLS with iron, dopamine and other neurotransmitter systems including the endogenous opiate, serotoninergic, glutamatergic and adenosinergic systems. We also explore the role of vitamin D in RLS Augmentation (i.e., the paradoxical worsening of RLS symptoms when dopaminergic agents are used as a therapy for RLS). Although the literature is not entirely consistent in affirming vitamin D deficiency in RLS or the amelioration of RLS symptoms with vitamin D therapy, the collective studies overall indicate that vitamin D deficiency is common enough in RLS patients to suggest that RLS patients should have their vitamin D levels checked and any deficiency corrected as a standard of care. Patients with Restless Legs Syndrome (RLS) may be deficient in vitamin D and therapy with vitamin D may ameliorate RLS. We present the first review dedicated solely to evaluating the relationship between RLS and vitamin D and present a case for the role of vitamin D in RLS pathogenesis.
Xu X, Ruan J, Tao T, Xiang S, Meng R, Chen X PLoS One. 2025; 20(3):e0313571.
PMID: 40063620 PMC: 11892881. DOI: 10.1371/journal.pone.0313571.
Unraveling the Bone-Brain Axis: A New Frontier in Parkinson's Disease Research.
Liu T, Wu H, Li J, Zhu C, Wei J Int J Mol Sci. 2024; 25(23).
PMID: 39684552 PMC: 11641043. DOI: 10.3390/ijms252312842.
Effects of Dietary Supplementation in Patients with Restless Legs Syndrome: A Systematic Review.
Gonzalez-Parejo P, Martin-Nunez J, Cabrera-Martos I, Valenza M Nutrients. 2024; 16(14).
PMID: 39064758 PMC: 11280425. DOI: 10.3390/nu16142315.
Gender medicine and sleep disorders: from basic science to clinical research.
Perger E, Silvestri R, Bonanni E, Di Perri M, Fernandes M, Provini F Front Neurol. 2024; 15:1392489.
PMID: 39050129 PMC: 11267506. DOI: 10.3389/fneur.2024.1392489.
Unveiling the pathophysiology of restless legs syndrome through transcriptome analysis.
Mogavero M, Salemi M, Lanza G, Rinaldi A, Marchese G, Ravo M iScience. 2024; 27(4):109568.
PMID: 38617564 PMC: 11015462. DOI: 10.1016/j.isci.2024.109568.