Skip to main content

Advertisement

SpringerLink
Log in

Efficacy of vitamin D replacement therapy in restless legs syndrome: a randomized control trial

  • Neurology • Original Article
  • Published:
Sleep and Breathing Aims and scope Submit manuscript

Abstract

Purpose

Restless legs syndrome is a movement sleep disorder that may be linked to dopaminergic dysfunction and in which vitamin D may play a role. This 12-week randomized, placebo-controlled trial elucidated the efficacy of vitamin D supplements in decreasing restless legs syndrome symptom severity.

Methods

Thirty-five subjects with restless legs syndrome, diagnosed using the International Restless Legs Syndrome Study Group criteria, were enrolled. The subjects were randomized to orally receive either vitamin D (50,000 IU caplets) or a placebo. All medications were administered weekly using a direct observation technique. Clinical assessments, including those for restless legs syndrome severity, were conducted at baseline and the end of the study using the International Restless Legs Syndrome Study Group rating scale. The serum vitamin D levels and bone profiles were measured at baseline and every 4 weeks. The primary endpoint was the change in the restless legs syndrome severity score from baseline to week 12. There were 17 and 18 patients in the vitamin D and placebo groups, respectively.

Results

The groups did not differ with respect to age, sex, restless legs syndrome severity, or vitamin D levels. Participants in the vitamin D group showed no significant change in the mean restless legs syndrome severity score compared with the placebo group.

Conclusions

The results suggest that vitamin D supplementation does not improve restless legs syndrome symptoms.

Clinical trial registration number

ClinicalTrials.gov: NCT02256215 (available from: https://clinicaltrials.gov/ct2/show/NCT02256215).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J, Restless Legs Syndrome Diagnosis and Epidemiology workshop at the National Institutes of Health, International Restless Legs Syndrome Study Group (2003) Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the Restless Legs Syndrome Diagnosis and Epidemiology workshop at the National Institutes of Health. Sleep Med 4:101–119

    Article  PubMed  Google Scholar 

  2. Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, Bell TJ, Ferini-Strambi L (2005) Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 165:1286–1292

    Article  PubMed  Google Scholar 

  3. Allen RP, Bharmal M, Calloway M (2011) Prevalence and disease burden of primary restless legs syndrome: results of a general population survey in the United States. Mov Disord 26:114–120

    Article  PubMed  Google Scholar 

  4. Berger K, Kurth T (2007) RLS epidemiology—frequencies, risk factors and methods in population studies. Mov Disord 22:S420–S423

    Article  PubMed  Google Scholar 

  5. Wali SO, Abaalkhail B (2015) Prevalence of restless legs syndrome and associated risk factors among middle-aged Saudi population. Ann Thorac Med 10:193–198

    Article  PubMed  PubMed Central  Google Scholar 

  6. Chokroverty S, Jankovic J (1999) Restless legs syndrome: a disease in search of identity. Neurology 5:907–910

    Article  Google Scholar 

  7. Turjanski N, Lees AJ, Brooks DJ (1999) Striatal dopaminergic function in restless legs syndrome: 18F-dopa and 11C-raclopride PET studies. Neurology 52:932–937

    Article  CAS  PubMed  Google Scholar 

  8. Montplaisir J, Nicolas A, Denesle R, Gomez-Mancilla B (1999) Restless legs syndrome improved by pramipexole: a double-blind randomized trial. Neurology 52:938–943

    Article  CAS  PubMed  Google Scholar 

  9. Prakash S, Bhanvadia RJ, Shah ND (2010) Restless legs syndrome with carbamazepine-induced osteomalacia: causal or casual association. Gen Hosp Psychiatry 32:228.e1–228.e3

    Article  Google Scholar 

  10. Wetter TC, Stiasny K, Winkelmann J, Buhlinger A, Brandenburg U, Penzel T, Medori R, Rubin M, Oertel WH, Trenkwalder C (1999) A randomized controlled study of pergolide in patients with restless legs syndrome. Neurology 52:944–950

    Article  CAS  PubMed  Google Scholar 

  11. Baksi SN, Hughes MJ (1982) Chronic vitamin D deficiency in the weanling rat alters catecholamine metabolism in the cortex. Brain Res 242:387–390

    Article  CAS  PubMed  Google Scholar 

  12. Ibi M, Sawada H, Nakanishi M, Kume T, Katsuki H, Kaneko S, Shimohama S, Akaike A (2001) Protective effects of 1,25-(OH)2D3 against the neurotoxicity of glutamate and reactive oxygen species in mesencephalic culture. Neuropharmacology 40:761–771

    Article  CAS  PubMed  Google Scholar 

  13. Garcion E, Sindji L, Leblondel G, Brachet P, Darcy F (1999) 1,25-Dihydroxyvitamin D3 regulates the synthesis of gamma-glutamyl transpeptidase and glutathione levels in rat primary astrocytes. J Neurochem 73:859–866

    Article  CAS  PubMed  Google Scholar 

  14. Nakamura K, Wang W, Kang UJ (1997) The role of glutathione in dopaminergic neuronal survival. J Neurochem 69:1850–1858

    Article  CAS  PubMed  Google Scholar 

  15. Cui X, Pelekanos M, Liu PY, Burne THJ, McGrath JJ, Eyles DW (2013) The vitamin D receptor in dopamine neurons; its presence in human substantia nigra and its ontogenesis in rat midbrain. Neuroscience 236:77–87

    Article  CAS  PubMed  Google Scholar 

  16. Orme RP, Bhangal MS, Fricker RA (2013) Calcitriol imparts neuroprotection in vitro to midbrain dopaminergic neurons by upregulating GDNF expression. PLoS One 8:e62040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Balaban H, Yıldız ÖK, Çil G, Şentürk İA, Erselcan T, Bolayır E, Topaktaş S (2012) Serum 25-hydroxyvitamin D levels in restless legs syndrome patients. Sleep Med 13:953–957

    Article  PubMed  Google Scholar 

  18. Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, Zucconi M, Ferri R, Trenkwalder C, Lee HB, International Restless Legs Syndrome Study Group (2014) Restless legs syndrome/Willis–Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria—history, rationale, description, and significance. Sleep Med 15:860–873

    Article  PubMed  Google Scholar 

  19. Wali S et al (2017) The effect of vitamin D replacement therapy in restless legs syndrome: a randomized trial. CHEST 152(4):A1069

    Article  Google Scholar 

  20. Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, Trenkwalder C, International Restless Legs Syndrome Study Group (2003) Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 4:121–132

    Article  PubMed  Google Scholar 

  21. Van Schoor NM, Lips P (2011) Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab 25:671–680

    Article  CAS  PubMed  Google Scholar 

  22. Lips P (2004) Which circulating level of 25-hydroxyvitamin D is appropriate? J Steroid Biochem Mol Biol 89-90:611–614

    Article  CAS  PubMed  Google Scholar 

  23. Abetz L, Arbuckle R, Allen RP, Garcia-Borreguero D, Hening W, Walters AS, Mavraki E, Kirsch JM (2006) The reliability, validity and responsiveness of the International Restless Legs Syndrome Study Group rating scale and subscales in a clinical-trial setting. Sleep Med 7:340–349

    Article  PubMed  Google Scholar 

  24. Ondo WG, Grieger F, Moran K, Kohnen R, Roth T (2016) Post hoc analysis of data from two clinical trials evaluating the minimal clinically important change in international restless legs syndrome sum score in patients with restless legs syndrome (Willis–Ekbom disease). J Clin Sleep Med 12:63–70

    Article  PubMed  PubMed Central  Google Scholar 

  25. Oran M, Unsal C, Albayrak Y, Tulubas F, Oguz K, Avci O, Turgut N, Alp R, Gurel A (2014) Possible association between vitamin D deficiency and restless legs syndrome. Neuropsychiatr Dis Treat 10:953–958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wali S, Shukr A, Boudal A et al (2015) The effect of vitamin D supplements on the severity of restless legs syndrome. Sleep Breath 19:579–583 Erratum in: sleep breath 2015, 1:1483

    Article  PubMed  Google Scholar 

  27. Wali S, Alsafadi S, Abaalkhail B, Ramadan I, Abulhamail B, Kousa M, Alshamrani R, Faruqui H, Faruqui A, Alama M, Hamed M (2018) The association between vitamin D level and restless legs syndrome: a population-based case–control study. J Clin Sleep Med 14:557–564

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We are grateful to the participants of the study. The authors would like to thank Dr. Ohoud Shakroon, Clinical Pharmacist, King Abdulaziz University Hospital, for her substantial assistance in providing the required medications. The authors greatly appreciate Drs. Mohamed Hamed, Khaled Aljammali, and Hanadi Sabbahi for their effort in collecting data. Finally, special thanks to Dr. Ghada Qadi for help with the preparation of the proposal and to Mrs. Walaa Abuzahra, Research Coordinator, Sleep Medicine and Research Center, for her time and effort in coordinating all procedures. The preliminary results of this study were presented at the Chest Annual Meeting 2017 (Wali SO, et al. Control ID 2729173. Presented at CHEST Annual Meeting, Oct 28–Nov 1, 2017, Toronto, ON, Canada).

Funding

This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah (grant no. G-1436-140-279). The authors acknowledge DSR with thanks for their technical and financial support. The funding source had no involvement in the study design, manuscript preparation, or decision to submit the article for publication.

Author information

Authors and Affiliations

  1. Sleep Medicine Research Group, Sleep Medicine and Research Center, College of Medicine, King Abdulaziz University Hospital, P.O. Box 21589, Jeddah, 80215, Saudi Arabia

    Siraj Omar Wali & Faris Alhejaili

  2. Family and Community Medicine Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia

    Bahaa Abaalkhail

  3. Somnogen Canada Inc., College Street, Toronto, ON, Canada

    S. R. Pandi-Perumal

Authors
  1. Siraj Omar Wali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bahaa Abaalkhail
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Faris Alhejaili
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. R. Pandi-Perumal
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Concept development: S.O.W. Study design: S.O.W. Data acquisition, supervision, data analysis, and interpretation: S.O.W., B.A., F.A. Manuscript preparation: S.O.W., B.A., F.A. Critical revision of the manuscript: S.O.W., S.R.P.-P. Prior to submission, all authors read and approved the final manuscript.

Corresponding author

Correspondence to Siraj Omar Wali.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethics approval and consent for participation

The study was approved by the Human Institutional Ethics Committee of King Abdulaziz University Hospital (Approval No. HA-02-J-008). Informed consent was obtained from all participants.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wali, S.O., Abaalkhail, B., Alhejaili, F. et al. Efficacy of vitamin D replacement therapy in restless legs syndrome: a randomized control trial. Sleep Breath 23, 595–601 (2019). https://doi.org/10.1007/s11325-018-1751-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11325-018-1751-2

Keywords

Search

Navigation