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

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

Open Access
|Apr 2023

References

  1. 1Restless Legs Syndrome Foundation. Understanding RLS 2018 [Available from: https://www.rls.org/understanding-rls.
  2. 2Ohayon MM, O’Hara R, Vitiello MV. Epidemiology of restless legs syndrome: a synthesis of the literature. Sleep Med Rev. 2012; 16(4): 28395. DOI: 10.1016/j.smrv.2011.05.002
  3. 3Allen RP, Bharmal M, Calloway M. Prevalence and disease burden of primary restless legs syndrome: results of a general population survey in the United States. Mov Disord. 2011; 26(1): 11420. DOI: 10.1002/mds.23430
  4. 4Dodel R, Happe S, Peglau I, Mayer G, Wasem J, Reese JP, et al. Health economic burden of patients with restless legs syndrome in a German ambulatory setting. Pharmacoeconomics. 2010; 28(5): 38193. DOI: 10.2165/11531030-000000000-00000
  5. 5Durgin T, Witt EA, Fishman J. The Humanistic and Economic Burden of Restless Legs Syndrome. PLoS One. 2015; 10(10): e0140632. DOI: 10.1371/journal.pone.0140632
  6. 6Didato G, Di Giacomo R, Rosa GJ, Dominese A, de Curtis M, Lanteri P. Restless Legs Syndrome across the Lifespan: Symptoms, Pathophysiology, Management and Daily Life Impact of the Different Patterns of Disease Presentation. Int J Environ Res Public Health. 2020; 17(10). DOI: 10.3390/ijerph17103658
  7. 7Smith EM, Tangpricha V. Vitamin D and anemia: insights into an emerging association. Curr Opin Endocrinol Diabetes Obes. 2015; 22(6): 4328. DOI: 10.1097/MED.0000000000000199
  8. 8Wali S, Alsafadi S, Abaalkhail B, Ramadan I, Abulhamail B, Kousa M, et al. The Association Between Vitamin D Level and Restless Legs Syndrome: A Population-Based Case-Control Study. J Clin Sleep Med. 2018; 14(4): 55764. DOI: 10.5664/jcsm.7044
  9. 9Baksi SN, Hughes MJ. Chronic vitamin D deficiency in the weanling rat alters catecholamine metabolism in the cortex. Brain Res. 1982; 242(2): 38790. DOI: 10.1016/0006-8993(82)90331-6
  10. 10Oran M, Unsal C, Albayrak Y, Tulubas F, Oguz K, Avci O, et al. Possible association between vitamin D deficiency and restless legs syndrome. Neuropsychiatr Dis Treat. 2014; 10: 9538. DOI: 10.2147/NDT.S63599
  11. 11Kesby JP, Cui X, O’Loan J, McGrath JJ, Burne TH, Eyles DW. Developmental vitamin D deficiency alters dopamine-mediated behaviors and dopamine transporter function in adult female rats. Psychopharmacology (Berl). 2010; 208(1): 15968. DOI: 10.1007/s00213-009-1717-y
  12. 12Jiménez-Jiménez FJ, Alonso-Navarro H, García-Martín E, Agúndez JAG. Neurochemical features of idiopathic restless legs syndrome. Sleep Med Rev. 2019; 45: 7087. DOI: 10.1016/j.smrv.2019.03.006
  13. 13Geng C, Yang Z, Kong X, Xu P, Zhang H. Correlation between vitamin D and poor sleep status in restless legs syndrome. Front Endocrinol (Lausanne). 2022; 13: 994545. DOI: 10.3389/fendo.2022.994545
  14. 14Mansourian M, Rafie N, Khorvash F, Hadi A, Arab A. Are serum vitamin D, calcium and phosphorous associated with restless leg syndrome? A systematic review and meta-analysis. Sleep Med. 2020; 75: 32634. DOI: 10.1016/j.sleep.2020.08.022
  15. 15Liu HM, Chu M, Liu CF, Zhang T, Gu P. Analysis of Serum Vitamin D Level and Related Factors in Patients With Restless Legs Syndrome. Front Neurol. 2021; 12: 782565. DOI: 10.3389/fneur.2021.782565
  16. 16Jiménez-Jiménez FJ, Amo G, Alonso-Navarro H, Calleja M, Díez-Fairén M, Álvarez-Fernández I, et al. Serum vitamin D, vitamin D receptor and binding protein genes polymorphisms in restless legs syndrome. J Neurol. 2021; 268(4): 146172. DOI: 10.1007/s00415-020-10312-9
  17. 17Balaban H, Yıldız Ö K, Çil G, Şentürk İ A, Erselcan T, Bolayır E, et al. Serum 25-hydroxyvitamin D levels in restless legs syndrome patients. Sleep Med. 2012; 13(7): 9537. DOI: 10.1016/j.sleep.2012.04.009
  18. 18Gupta R, Dhyani M, Kendzerska T, Pandi-Perumal SR, BaHammam AS, Srivanitchapoom P, et al. Restless legs syndrome and pregnancy: prevalence, possible pathophysiological mechanisms and treatment. Acta Neurol Scand. 2016; 133(5): 3209. DOI: 10.1111/ane.12520
  19. 19Almeneessie AS, Alyousefi N, Alzahrani M, Alsafi A, Alotaibi R, Olaish AH, et al. Prevalence of restless legs syndrome among pregnant women: A case-control study. Ann Thorac Med. 2020; 15(1): 914. DOI: 10.4103/atm.ATM_206_19
  20. 20Miyazaki A, Takahashi M, Shuo T, Eto H, Kondo H. Determination of optimal 25-hydroxyvitamin D cutoff values for the evaluation of restless legs syndrome among pregnant women. J Clin Sleep Med. 2023; 19(1): 7383. DOI: 10.5664/jcsm.10270
  21. 21Almeneessier AS, Alzahrani M, Alsafi A, Alotaibi R, Olaish AH, BaHammam AS. Prevalence and predictors of restless legs syndrome in non-pregnant Saudi women of childbearing age. Sleep Breath. 2020; 24(3): 110713. DOI: 10.1007/s11325-020-02054-9
  22. 22Bener A, Al-Hamaq A, Ağan AF, Öztürk M, Ömer A. The prevalence of restless legs syndrome and comorbid condition among patient with type 2 diabetic mellitus visiting primary healthcare. J Family Med Prim Care. 2019; 8(12): 381420. DOI: 10.4103/jfmpc.jfmpc_463_19
  23. 23Olama SM, Senna MK, Elarman MM, Elhawary G. Serum vitamin D level and bone mineral density in premenopausal Egyptian women with fibromyalgia. Rheumatol Int. 2013; 33(1): 18592. DOI: 10.1007/s00296-012-2361-0
  24. 24Prono F, Bernardi K, Ferri R, Bruni O. The Role of Vitamin D in Sleep Disorders of Children and Adolescents: A Systematic Review. Int J Mol Sci. 2022; 23(3). DOI: 10.3390/ijms23031430
  25. 25Evans AM, Berde T, Karimi L, Ranade P, Shah N, Khubchandani R. Correlates and predictors of paediatric leg pain: a case-control study. Rheumatol Int. 2018; 38(7): 12518. DOI: 10.1007/s00296-018-4056-7
  26. 26Walters AS, Gabelia D, Frauscher B. Restless legs syndrome (Willis-Ekbom disease) and growing pains: are they the same thing? A side-by-side comparison of the diagnostic criteria for both and recommendations for future research. Sleep Med. 2013; 14(12): 124752. DOI: 10.1016/j.sleep.2013.07.013
  27. 27IŞıkay S, IŞıkay N, Per H, Çarman KB, Kocamaz H. Restless leg syndrome in children with celiac disease. Turk J Pediatr. 2018; 60(1): 705. DOI: 10.24953/turkjped.2018.01.010
  28. 28Çakır T, Doğan G, SubaŞı V, Filiz MB, Ülker N, Doğan Ş K, et al. An evaluation of sleep quality and the prevalence of restless leg syndrome in vitamin D deficiency. Acta Neurol Belg. 2015; 115(4): 6237. DOI: 10.1007/s13760-015-0474-4
  29. 29Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J. 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. 2003; 4(2): 10119. DOI: 10.1016/S1389-9457(03)00010-8
  30. 30Sun S, Liu C, Jia Y, Wu J, Li H, Li X, et al. Association Between Migraine Complicated With Restless Legs Syndrome and Vitamin D. Front Neurol. 2021; 12: 777721. DOI: 10.3389/fneur.2021.777721
  31. 31Neves PD, Graciolli FG, Oliveira IB, Bridi RA, Moysés RM, Elias RM. Effect of Mineral and Bone Metabolism on Restless Legs Syndrome in Hemodialysis Patients. J Clin Sleep Med. 2017; 13(1): 8994. DOI: 10.5664/jcsm.6396
  32. 32Wali SO, Abaalkhail B, Alhejaili F, Pandi-Perumal SR. Efficacy of vitamin D replacement therapy in restless legs syndrome: a randomized control trial. Sleep Breath. 2019; 23(2): 595601. DOI: 10.1007/s11325-018-1751-2
  33. 33Buratti L, Luconi MP, Viticchi G, Provinciali L, Silvestrini M. Vitamin D supplementation: a useful strategy for restless legs syndrome exacerbation in a patient with Turner syndrome. Neurol Sci. 2017; 38(6): 11356. DOI: 10.1007/s10072-017-2870-4
  34. 34Wali S, Shukr A, Boudal A, Alsaiari A, Krayem A. The effect of vitamin D supplements on the severity of restless legs syndrome. Sleep Breath. 2015; 19(2): 57983. DOI: 10.1007/s11325-014-1049-y
  35. 35Tutuncu M, Tutuncu M. The effect of vitamin D on restless legs syndrome: prospective self-controlled case study. Sleep Breath. 2020; 24(3): 11016. DOI: 10.1007/s11325-019-01984-3
  36. 36Dijk DJ. Biomarkers, old and new: for sleep, sleepiness, circadian phase and much more…. J Sleep Res. 2016; 25(3): 2556. DOI: 10.1111/jsr.12435
  37. 37Mondello S, Kobeissy FH, Mechref Y, Zhao J, El Hayek S, Zibara K, et al. Searching for Novel Candidate Biomarkers of RLS in Blood by Proteomic Analysis. Nat Sci Sleep. 2021; 13: 87383. DOI: 10.2147/NSS.S311801
  38. 38Patton SM, Cho YW, Clardy TW, Allen RP, Earley CJ, Connor JR. Proteomic analysis of the cerebrospinal fluid of patients with restless legs syndrome/Willis-Ekbom disease. Fluids Barriers CNS. 2013; 10(1): 20. DOI: 10.1186/2045-8118-10-20
  39. 39Shin JW, Lee JH, Kim H, Lee DH, Baek KH, Sunwoo JS, et al. Bioinformatic analysis of proteomic data for iron, inflammation, and hypoxic pathways in restless legs syndrome. Sleep Med. 2020; 75: 44855. DOI: 10.1016/j.sleep.2020.09.002
  40. 40Bellei E, Monari E, Ozben S, Koseoglu Bitnel M, Topaloglu Tuac S, Tomasi A, et al. Discovery of restless legs syndrome plasmatic biomarkers by proteomic analysis. Brain Behav. 2018; 8(10): e01062. DOI: 10.1002/brb3.1062
  41. 41Bikle DD, Schwartz J. Vitamin D Binding Protein, Total and Free Vitamin D Levels in Different Physiological and Pathophysiological Conditions. Front Endocrinol (Lausanne). 2019; 10: 317. DOI: 10.3389/fendo.2019.00317
  42. 42Jiménez-Jiménez FJ, García-Martín E, Alonso-Navarro H, Martínez C, Zurdo M, Turpín-Fenoll L, et al. Association Between Vitamin D Receptor rs731236 (Taq1) Polymorphism and Risk for Restless Legs Syndrome in the Spanish Caucasian Population. Medicine (Baltimore). 2015; 94(47): e2125. DOI: 10.1097/MD.0000000000002125
  43. 43Sarayloo F, Dionne-Laporte A, Catoire H, Rochefort D, Houle G, Ross JP, et al. Mineral absorption is an enriched pathway in a brain region of restless legs syndrome patients with reduced MEIS1 expression. PLoS One. 2019; 14(11): e0225186. DOI: 10.1371/journal.pone.0225186
  44. 44Giustina A, Bouillon R, Dawson-Hughes B, Ebeling PR, Lazaretti-Castro M, Lips P, et al. Vitamin D in the older population: a consensus statement. Endocrine. 2023; 79(1): 3144. DOI: 10.1007/s12020-022-03208-3
  45. 45Fuleihan G, Silverberg SJ. Primary hyperparathyroidism: diagnosis, differential diagnosis, and evaluation. UpToDate UpToDate, Waltham (Accessed on July 14, 2016); 2018.
  46. 46Mao S, Shen H, Huang S, Zhang A. Restless legs syndrome in dialysis patients: a meta-analysis. Sleep medicine. 2014; 15(12): 15328. DOI: 10.1016/j.sleep.2014.07.017
  47. 47Santos RS, Coelho FM, da Silva BC, Graciolli FG, Dominguez WV, de Menezes Montenegro FL, et al. Parathyroidectomy Improves Restless Leg Syndrome in Patients on Hemodialysis. PLoS One. 2016; 11(5): e0155835. DOI: 10.1371/journal.pone.0155835
  48. 48Schneider R, Karakas E, Bartsch DK, Schlosser K. The influence of parathyroidectomy on restless legs syndrome in patients with renal hyperparathyroidism. World journal of surgery. 2013; 37(12): 286671. DOI: 10.1007/s00268-013-2185-4
  49. 49Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effects of 1, 25-dihydroxyvitamin D3 on human B cell differentiation. The Journal of Immunology. 2007; 179(3): 163447. DOI: 10.4049/jimmunol.179.3.1634
  50. 50Rolf L, Muris AH, Hupperts R, Damoiseaux J. Illuminating vitamin D effects on B cells–the multiple sclerosis perspective. Immunology. 2016; 147(3): 27584. DOI: 10.1111/imm.12572
  51. 51Ao T, Kikuta J, Ishii M. The Effects of Vitamin D on Immune System and Inflammatory Diseases. Biomolecules. 2021; 11(11). DOI: 10.3390/biom11111624
  52. 52Weinstock LB, Walters AS, Paueksakon P. Restless legs syndrome—theoretical roles of inflammatory and immune mechanisms. Sleep Med Rev. 2012; 16(4): 34154. DOI: 10.1016/j.smrv.2011.09.003
  53. 53Higuchi T, Abe M, Mizuno M, Yamazaki T, Suzuki H, Moriuchi M, et al. Association of restless legs syndrome with oxidative stress and inflammation in patients undergoing hemodialysis. Sleep medicine. 2015; 16(8): 9418. DOI: 10.1016/j.sleep.2015.03.025
  54. 54Hennessy MD, Zak RS, Gay CL, Pullinger CR, Lee KA, Aouizerat BE. Polymorphisms of interleukin-1 Beta and interleukin-17Alpha genes are associated with restless legs syndrome. Biol Res Nurs. 2014; 16(2): 14351. DOI: 10.1177/1099800413478827
  55. 55Weinstock LB, Brook JB, Walters AS, Goris A, Afrin LB, Molderings GJ. Restless legs syndrome is associated with long-COVID in women. J Clin Sleep Med. 2022; 18(5): 14138. DOI: 10.5664/jcsm.9898
  56. 56de la Guía-Galipienso F, Martínez-Ferran M, Vallecillo N, Lavie CJ, Sanchis-Gomar F, Pareja-Galeano H. Vitamin D and cardiovascular health. Clin Nutr. 2021; 40(5): 294657. DOI: 10.1016/j.clnu.2020.12.025
  57. 57Kim HA, Perrelli A, Ragni A, Retta F, De Silva TM, Sobey CG, et al. Vitamin D Deficiency and the Risk of Cerebrovascular Disease. Antioxidants (Basel). 2020; 9(4). DOI: 10.3390/antiox9040327
  58. 58Rihal V, Khan H, Kaur A, Singh TG. Vitamin D as therapeutic modulator in cerebrovascular diseases: a mechanistic perspectives. Crit Rev Food Sci Nutr. 2022; 123. DOI: 10.1080/10408398.2022.2050349
  59. 59Siniscalchi A, Lochner P, Anticoli S, Chirchiglia D, De Sarro G, Gallelli L. What is the Current Role for Vitamin D and the Risk of Stroke? Curr Neurovasc Res. 2019; 16(2): 17883. DOI: 10.2174/1567202616666190412152948
  60. 60Walters AS, Rye DB. Review of the relationship of restless legs syndrome and periodic limb movements in sleep to hypertension, heart disease, and stroke. Sleep. 2009; 32(5): 58997. DOI: 10.1093/sleep/32.5.589
  61. 61May AM, May RD, Bena J, Wang L, Monahan K, Stone KL, et al. Individual periodic limb movements with arousal are temporally associated with nonsustained ventricular tachycardia: a case-crossover analysis. Sleep. 2019; 42(11).
  62. 62Mirza M, Shen WK, Sofi A, Tran C, Jahangir A, Sultan S, et al. Frequent periodic leg movement during sleep is an unrecognized risk factor for progression of atrial fibrillation. PLoS One. 2013; 8(10): e78359. DOI: 10.1371/journal.pone.0078359
  63. 63Mirza M, Shen WK, Sofi A, Jahangir A, Mori N, Tajik AJ, et al. Frequent periodic leg movement during sleep is associated with left ventricular hypertrophy and adverse cardiovascular outcomes. J Am Soc Echocardiogr. 2013; 26(7): 78390. DOI: 10.1016/j.echo.2013.03.018
  64. 64Giannaki CD, Zigoulis P, Karatzaferi C, Hadjigeorgiou GM, George KP, Gourgoulianis K, et al. Periodic limb movements in sleep contribute to further cardiac structure abnormalities in hemodialysis patients with restless legs syndrome. J Clin Sleep Med. 2013; 9(2): 14753. DOI: 10.5664/jcsm.2412
  65. 65Yoshihisa A, Misaka T, Kanno Y, Yokokawa T, Sato T, Oikawa M, et al. Prognostic Impact of Restless Legs Syndrome on Patients with Heart Failure. Int Heart J. 2019; 60(5): 1098105. DOI: 10.1536/ihj.19-049
  66. 66Baskol G, Korkmaz S, Erdem F, Caniklioglu A, Kocyigit M, Aksu M. Assessment of nitric oxide, advanced oxidation protein products, malondialdehyde, and thiol levels in patients with restless legs syndrome. Sleep Med. 2012; 13(4): 4148. DOI: 10.1016/j.sleep.2011.11.012
  67. 67Kucuksayan E, Ozben S, Topaloglu Tuac S, Koseoglu M, Erel O, Neselioglu S, et al. Plasma thiol/disulphide homeostasis changes in patients with restless legs syndrome. Clin Chem Lab Med. 2021; 59(7): 125765. DOI: 10.1515/cclm-2020-1659
  68. 68Cikrikcioglu MA, Hursitoglu M, Erkal H, Kınas BE, Sztajzel J, Cakirca M, et al. Oxidative stress and autonomic nervous system functions in restless legs syndrome. Eur J Clin Invest. 2011; 41(7): 73442. DOI: 10.1111/j.1365-2362.2010.02461.x
  69. 69Bellei E, Bergamini S, Monari E, Tomasi A, Koseoglu M, Topaloglu Tuac S, et al. Evaluation of potential cardiovascular risk protein biomarkers in high severity restless legs syndrome. J Neural Transm (Vienna). 2019; 126(10): 131320. DOI: 10.1007/s00702-019-02051-7
  70. 70Ferri R, Cosentino FI, Moussouttas M, Lanuzza B, Aricò D, Bagai K, et al. Silent cerebral small vessel disease in restless legs syndrome. Sleep. 2016; 39(7): 13717. DOI: 10.5665/sleep.5966
  71. 71Walters AS, Paueksakon P, Adler CH, Moussouttas M, Weinstock LB, Spruyt K, et al. Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis. J Am Heart Assoc. 2021; 10(11): e019627. DOI: 10.1161/JAHA.120.019627
  72. 72Boulos MI, Murray BJ, Muir RT, Gao F, Szilagyi GM, Huroy M, et al. Periodic Limb Movements and White Matter Hyperintensities in First-Ever Minor Stroke or High-Risk Transient Ischemic Attack. Sleep. 2017; 40(3). DOI: 10.1093/sleep/zsw080
  73. 73Gao X, Ba DM, Bagai K, Liu G, Ma C, Walters AS. Treating Restless Legs Syndrome Was Associated With Low Risk of Cardiovascular Disease: A Cohort Study With 3.4 Years of Follow-Up. J Am Heart Assoc. 2021; 10(4): e018674. DOI: 10.1161/JAHA.120.018674
  74. 74Connor JR, Wang XS, Allen RP, Beard JL, Wiesinger JA, Felt BT, et al. Altered dopaminergic profile in the putamen and substantia nigra in restless leg syndrome. Brain. 2009; 132(Pt 9): 240312. DOI: 10.1093/brain/awp125
  75. 75Rizzo G, Plazzi G. Neuroimaging Applications in Restless Legs Syndrome. Int Rev Neurobiol. 2018; 143: 3164. DOI: 10.1016/bs.irn.2018.09.012
  76. 76Ibi M, Sawada H, Nakanishi M, Kume T, Katsuki H, Kaneko S, et al. Protective effects of 1 alpha,25-(OH)(2)D(3) against the neurotoxicity of glutamate and reactive oxygen species in mesencephalic culture. Neuropharmacology. 2001; 40(6): 76171. DOI: 10.1016/S0028-3908(01)00009-0
  77. 77Goulart LI, Delgado Rodrigues RN, Prieto Peres MF. Restless legs syndrome and pain disorders: what’s in common? Curr Pain Headache Rep. 2014; 18(11): 461. DOI: 10.1007/s11916-014-0461-0
  78. 78Cui X, Pelekanos M, Liu PY, Burne TH, McGrath JJ, Eyles DW. The vitamin D receptor in dopamine neurons; its presence in human substantia nigra and its ontogenesis in rat midbrain. Neuroscience. 2013; 236: 7787. DOI: 10.1016/j.neuroscience.2013.01.035
  79. 79Eyles DW, Burne TH, McGrath JJ. Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol. 2013; 34(1): 4764. DOI: 10.1016/j.yfrne.2012.07.001
  80. 80Seyedi M, Gholami F, Samadi M, Djalali M, Effatpanah M, Yekaninejad MS, et al. The Effect of Vitamin D3 Supplementation on Serum BDNF, Dopamine, and Serotonin in Children with Attention-Deficit/Hyperactivity Disorder. CNS Neurol Disord Drug Targets. 2019; 18(6): 496501. DOI: 10.2174/1871527318666190703103709
  81. 81Trenkwalder C, Beneš H, Grote L, García-Borreguero D, Högl B, Hopp M, et al. Prolonged release oxycodone-naloxone for treatment of severe restless legs syndrome after failure of previous treatment: a double-blind, randomised, placebo-controlled trial with an open-label extension. Lancet Neurol. 2013; 12(12): 114150. DOI: 10.1016/S1474-4422(13)70239-4
  82. 82Walters AS, Ondo WG, Zhu W, Le W. Does the endogenous opiate system play a role in the Restless Legs Syndrome? A pilot post-mortem study. J Neurol Sci. 2009; 279(1-2): 625. DOI: 10.1016/j.jns.2008.12.022
  83. 83Lyu S, DeAndrade MP, Mueller S, Oksche A, Walters AS, Li Y. Hyperactivity, dopaminergic abnormalities, iron deficiency and anemia in an in vivo opioid receptors knockout mouse: Implications for the restless legs syndrome. Behav Brain Res. 2019; 374: 112123. DOI: 10.1016/j.bbr.2019.112123
  84. 84Lyu S, DeAndrade MP, Unger EL, Mueller S, Oksche A, Walters AS, et al. Mu opioid receptor knockout mouse: Phenotypes with implications on restless legs syndrome. J Neurosci Res. 2020; 98(8): 153248. DOI: 10.1002/jnr.24637
  85. 85Walters AS, Li Y, Karroum EG, Champion D, Weinstock LB, Bagai K, et al. Exploring the role of the endogenous opiate system in the pathogenesis of anemia in an opiate receptor knock-out model of Restless Legs Syndrome. Med Hypotheses. 2022; 167. DOI: 10.1016/j.mehy.2022.110941
  86. 86Rokyta R, Fricová J. Ontogeny of the pain. Physiol Res. 2012; 61(Suppl 1): S10922. DOI: 10.33549/physiolres.932367
  87. 87Habib AM, Nagi K, Thillaiappan NB, Sukumaran V, Akhtar S. Vitamin D and Its Potential Interplay With Pain Signaling Pathways. Front Immunol. 2020; 11: 820. DOI: 10.3389/fimmu.2020.00820
  88. 88Poisbeau P, Aouad M, Gazzo G, Lacaud A, Kemmel V, Landel V, et al. Cholecalciferol (Vitamin D(3)) Reduces Rat Neuropathic Pain by Modulating Opioid Signaling. Mol Neurobiol. 2019; 56(10): 720821. DOI: 10.1007/s12035-019-1582-6
  89. 89Jhoo JH, Yoon IY, Kim YK, Chung S, Kim JM, Lee SB, et al. Availability of brain serotonin transporters in patients with restless legs syndrome. Neurology. 2010; 74(6): 5138. DOI: 10.1212/WNL.0b013e3181cef824
  90. 90Wang Y, Miller JW, Bello NT, Shapses SA. Low-vitamin-D diet lowers cerebral serotonin concentration in mature female mice. Nutr Res. 2020; 81: 7180. DOI: 10.1016/j.nutres.2020.07.006
  91. 91Huiberts LM, Smolders K. Effects of vitamin D on mood and sleep in the healthy population: Interpretations from the serotonergic pathway. Sleep Med Rev. 2021; 55: 101379. DOI: 10.1016/j.smrv.2020.101379
  92. 92Alghamdi S, Alsulami N, Khoja S, Alsufiani H, Tayeb HO, Tarazi FI. Vitamin D Supplementation Ameliorates Severity of Major Depressive Disorder. J Mol Neurosci. 2020; 70(2): 2305. DOI: 10.1007/s12031-019-01461-2
  93. 93Ferré S, Earley C, Gulyani S, Garcia-Borreguero D. In search of alternatives to dopaminergic ligands for the treatment of restless legs syndrome: iron, glutamate, and adenosine. Sleep Med. 2017; 31: 8692. DOI: 10.1016/j.sleep.2016.08.019
  94. 94Garcia-Borreguero D, Larrosa O, de la Llave Y, Verger K, Masramon X, Hernandez G. Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study. Neurology. 2002; 59(10): 15739. DOI: 10.1212/WNL.59.10.1573
  95. 95Kushida CA, Becker PM, Ellenbogen AL, Canafax DM, Barrett RW. Randomized, double-blind, placebo-controlled study of XP13512/GSK1838262 in patients with RLS. Neurology. 2009; 72(5): 43946. DOI: 10.1212/01.wnl.0000341770.91926.cc
  96. 96Allen RP, Chen C, Garcia-Borreguero D, Polo O, DuBrava S, Miceli J, et al. Comparison of pregabalin with pramipexole for restless legs syndrome. N Engl J Med. 2014; 370(7): 62131. DOI: 10.1056/NEJMoa1303646
  97. 97Allen RP, Barker PB, Horská A, Earley CJ. Thalamic glutamate/glutamine in restless legs syndrome: increased and related to disturbed sleep. Neurology. 2013; 80(22): 202834. DOI: 10.1212/WNL.0b013e318294b3f6
  98. 98Krisanova N, Pozdnyakova N, Pastukhov A, Dudarenko M, Maksymchuk O, Parkhomets P, et al. Vitamin D3 deficiency in puberty rats causes presynaptic malfunctioning through alterations in exocytotic release and uptake of glutamate/GABA and expression of EAAC-1/GAT-3 transporters. Food Chem Toxicol. 2019; 123: 14250. DOI: 10.1016/j.fct.2018.10.054
  99. 99Kasatkina LA, Tarasenko AS, Krupko OO, Kuchmerovska TM, Lisakovska OO, Trikash IO. Vitamin D deficiency induces the excitation/inhibition brain imbalance and the proinflammatory shift. Int J Biochem Cell Biol. 2020; 119: 105665. DOI: 10.1016/j.biocel.2019.105665
  100. 100Garcia-Borreguero D, Garcia-Malo C, Granizo JJ, Ferré S. A Randomized, Placebo-Controlled Crossover Study with Dipyridamole for Restless Legs Syndrome. Mov Disord. 2021; 36(10): 238792. DOI: 10.1002/mds.28668
  101. 101Antonioli L, Pacher P, Haskó G. Adenosine and inflammation: it’s time to (re)solve the problem. Trends Pharmacol Sci. 2022; 43(1): 4355. DOI: 10.1016/j.tips.2021.10.010
  102. 102Olabiyi AA, Passos DF, da Silva JLG, Schetinger MRC, Rosa Leal DB. Role of purinergic system and vitamin D in the anti-cancer immune response. Life Sci. 2021; 287: 120110. DOI: 10.1016/j.lfs.2021.120110
  103. 103da Silva JLG, Passos DF, Bernardes VM, Cabral FL, Schimites PG, Manzoni AG, et al. Co-Nanoencapsulation of Vitamin D(3) and Curcumin Regulates Inflammation and Purine Metabolism in a Model of Arthritis. Inflammation. 2019; 42(5): 1595610. DOI: 10.1007/s10753-019-01021-1
  104. 104Dankers W, Colin EM, van Hamburg JP, Lubberts E. Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential. Front Immunol. 2016; 7: 697. DOI: 10.3389/fimmu.2016.00697
  105. 105Bae H, Cho YW, Kim KT, Allen RP, Earley CJ. Randomized, placebo-controlled trial of ferric carboxymaltose in restless legs syndrome patients with iron deficiency anemia. Sleep Med. 2021; 84: 17986. DOI: 10.1016/j.sleep.2021.05.036
  106. 106Connor JR, Patton SM, Oexle K, Allen RP. Iron and restless legs syndrome: treatment, genetics and pathophysiology. Sleep Med. 2017; 31: 6170. DOI: 10.1016/j.sleep.2016.07.028
  107. 107Bacchetta J, Zaritsky JJ, Sea JL, Chun RF, Lisse TS, Zavala K, et al. Suppression of iron-regulatory hepcidin by vitamin D. J Am Soc Nephrol. 2014; 25(3): 56472. DOI: 10.1681/ASN.2013040355
  108. 108Hamed SA. Neurologic conditions and disorders of uremic syndrome of chronic kidney disease: presentations, causes, and treatment strategies. Expert Rev Clin Pharmacol. 2019; 12(1): 6190. DOI: 10.1080/17512433.2019.1555468
  109. 109Diker S. Restless Leg Syndrome: Role of Iron and Vitamin D Deficiencies. Cyprus Journal of Medical Sciences. 2018; 3(2): 1146. DOI: 10.5152/cjms.2018.347
  110. 110Kaviani M, Nikooyeh B, Zand H, Yaghmaei P, Neyestani TR. Effects of vitamin D supplementation on depression and some involved neurotransmitters. J Affect Disord. 2020; 269: 2835. DOI: 10.1016/j.jad.2020.03.029
  111. 111Salminen AV, Clemens S, García-Borreguero D, Ghorayeb I, Li Y, Manconi M, et al. Consensus guidelines on the construct validity of rodent models of restless legs syndrome. Dis Model Mech. 2022; 15(8). DOI: 10.1242/dmm.049615
  112. 112Salminen AV, Silvani A, Allen RP, Clemens S, Garcia-Borreguero D, Ghorayeb I, et al. Consensus Guidelines on Rodent Models of Restless Legs Syndrome. Mov Disord. 2021; 36(3): 55869. DOI: 10.1002/mds.28401
  113. 113Silvani A, Ghorayeb I, Manconi M, Li Y, Clemens S. Putative Animal Models of Restless Legs Syndrome: A Systematic Review and Evaluation of Their Face and Construct Validity. Neurotherapeutics; 2022. DOI: 10.1007/s13311-022-01334-4
  114. 114Bondu JD, Seshadri MS, Selvakumar R, Fleming JJ. Effects of Fluoride on Bone in an Animal Model of Vitamin D Deficiency. Indian J Clin Biochem. 2019; 34(1): 607.
  115. 115Kong M, Zhu L, Bai L, Zhang X, Chen Y, Liu S, et al. Vitamin D deficiency promotes nonalcoholic steatohepatitis through impaired enterohepatic circulation in animal model. Am J Physiol Gastrointest Liver Physiol. 2014; 307(9): G88393. DOI: 10.1152/ajpgi.00427.2013
  116. 116Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, et al. 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. 2014; 15(8): 86073. DOI: 10.1016/j.sleep.2014.03.025
  117. 117Walters AS. Toward a better definition of the restless legs syndrome. The International Restless Legs Syndrome Study Group. Mov Disord. 1995; 10(5): 63442.
  118. 118American Academy of Sleep Medicine. International Classification of Sleep Disorders, 3rd Edition (ICSD-3). Medicine AAoS, editor; 2015.
  119. 119Kondo H, Okada M, Eto H. Development of Cambridge-Hopkins questionnaire 13 Japanese version short form (CH-RLSq13) version 2.1 in the assessment of restless legs syndrome (in Japanese). Jpn J Sleep Med. 2016; 10(4): 57784.
  120. 120Evans AM, Scutter SD. Prevalence of “growing pains” in young children. J Pediatr. 2004; 145(2): 2558. DOI: 10.1016/j.jpeds.2004.04.045
  121. 121Jenkins CD, Stanton BA, Niemcryk SJ, Rose RM. A scale for the estimation of sleep problems in clinical research. J Clin Epidemiol. 1988; 41(4): 31321. DOI: 10.1016/0895-4356(88)90138-2
DOI: https://doi.org/10.5334/tohm.741 | Journal eISSN: 2160-8288
Language: English
Submitted on: Dec 12, 2022
Accepted on: Mar 16, 2023
Published on: Apr 6, 2023
Published by: Ubiquity Press
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year

© 2023 Katie L. J. Cederberg, Rosalia Silvestri, Arthur S. Walters, published by Ubiquity Press
This work is licensed under the Creative Commons Attribution 4.0 License.