Vitamin D and Restless Legs Syndrome: A Review of Current Literature

Tremor Other Hyperkinet Mov (N Y). 2023 Apr 6:13:12. doi: 10.5334/tohm.741. eCollection 2023.


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. Highlights 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.

Keywords: adenosine; augmentation; calcium; cardiovascular disease; cerebrovascular disease; dopamine; endogenous opiate system; genetics; glutamate; inflammation; iron; parathyroid hormone; phosphorus; proteomics; restless legs syndrome; serotonin; vitamin D; vitamin D binding protein.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dopamine / metabolism
  • Humans
  • Proteomics
  • Restless Legs Syndrome* / drug therapy
  • Restless Legs Syndrome* / epidemiology
  • Vitamin D / therapeutic use
  • Vitamin D Deficiency* / complications
  • Vitamin D Deficiency* / drug therapy
  • Vitamin D Deficiency* / epidemiology


  • Vitamin D
  • Dopamine