Evidence for the Importance of Vitamin D Status in Neurologic Conditions

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Opinion statement

Vitamin D status has been proposed as relevant to many neurological disorders. Data suggest that vitamin D may be important for the development of the nervous system, and it also plays a role in neuroimmunology and neuroprotection. Lower levels of circulating 25-hydroxyvitamin D have been linked with increased risk of multiple sclerosis (MS) and Alzheimer’s disease (AD). While people with amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and stroke have lower vitamin D levels than those without the diseases, it is unclear if this is because hypovitaminosis D contributes to disease risk or is a consequence of immobility and other factors caused by the disease. Lower levels of vitamin D have been associated with worse prognosis in MS, PD, ALS, and stroke, while no longitudinal studies have been performed to evaluate such an association in AD. Small pilot trials have been performed to evaluate vitamin D supplementation for some of these diseases, but there have been no phase III studies to support vitamin D supplementation in these patient populations; further, ideal levels of 25-hydroxyvitamin D are not known. Thus, while some expert panels or individuals have suggested routine testing and supplementation for patients with these neurological conditions, it is our opinion that there are currently insufficient data to support high-dose vitamin D supplementation to specifically treat or prevent these conditions.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as •• Of importance

  1. 1.

    Fernandes de Abreu DA, Eyles D, Féron F. Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases. Psycho Neuro Endocrinol. 2009;34(Suppl1):S265–77.

    CAS  Article  Google Scholar 

  2. 2.

    Falkenstein E et al. Multiple actions of steroid hormones—a focus on rapid, nongenomic effects. Pharmacol Rev. 2000;52:513–56.

    CAS  PubMed  Google Scholar 

  3. 3.

    Khanal R, Nemere I. Membrane receptors for vitamin D metabolites. Crit Rev Eukaryot Gene Expr. 2007;17:31–47.

    CAS  PubMed  Article  Google Scholar 

  4. 4.

    Burkert R, McGrath J, Eyles D. Vitamin D receptor expression in the embryonic rat brain. Neurosci Res Commun. 2003;33:63–71.

    CAS  Article  Google Scholar 

  5. 5.

    Eyles DW et al. Distribution of the vitamin D receptor and 1α-hydroxylase in human brain. J Chem Neuroanat. 2005;29:21–30.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Tohda C et al. Diosgenin-induced cognitive enhancement in normal mice is mediated by 1,25D3-MARRS. Sci Rep. 2013;5:3395.

    Google Scholar 

  7. 7.

    Baas D et al. Rat oligodendrocytes express the vitamin D3 receptor and respond to 1,25-dihydroxyvitamin D3. Glia. 2000;31(1):59–68.

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Eyles D et al. Vitamin D3 and brain development. Neuroscience. 2003;118:641–53.

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Feron F et al. Developmental vitamin D3 deficiency alters the adult rat brain. Brain Res Bull. 2005;65:141–8.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Harms LR et al. Developmental vitamin D deficiency alters adult behaviour in 129/SvJ and C57BL/6 J mice. Behav Brain Res. 2008;187:343–50.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Shirazi HA et al. 1,25-Dihydroxyvitamin D3 enhances neural stem cell proliferation and oligodendrocyte differentiation. Exp Mol Pathol. 2015;98(2):240–5.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Brown J et al. 1,25-Dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neurosci Lett. 2003;343:139–43.

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Latimer CS et al. Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats. Proc Natl Acad Sci U S A. 2014;111(41):E4359–66.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  14. 14.

    Landfield PW, Cadwallader-Neal L. Long-term treatment with calcitriol (1,25(OH)2 vit D3) retards a biomarker of hippocampal aging in rats. Neurobiol Aging. 1998;19(5):469–77.

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Wang Y et al. Vitamin D3 attenuates cortical infarction induced by middle cerebral arterial ligation in rats. Neuropharmacology. 2000;39(5):873–80.

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Balden R, Selvamani A, Sohrabji F. Vitamin D deficiency exacerbates experimental stroke injury and dysregulates ischemia-induced inflammation in adult rats. Endocrinology. 2012;153(5):2420–35.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  17. 17.

    Brewer LD et al. Vitamin D hormone confers neuroprotection in parallel with downregulation of L-type calcium channel expression in hippocampal neurons. J Neurosci. 2001;21(1):98–108.

    CAS  PubMed  Google Scholar 

  18. 18.

    Garcion E et al. 1,25-Dihydroxyvitamin D3 inhibits the expression of inducible nitric oxide synthase in rat central nervous system during experimental allergic encephalomyelitis. Brain Res Mol Brain Res. 1997;45(2):255–67.

    CAS  PubMed  Article  Google Scholar 

  19. 19.••

    Korf H et al. 1,25-Dihydroxyvitamin D3 curtails the inflammatory and T cell stimulatory capacity of macrophages through an IL-10-dependent mechanism. Immunobiology. 2012;217(12):1292–300. This article provided strong evidence for the anti-inflammatory effect of vitamin D on macrophages.

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Dursun E, Gezen-AK D, Yilmazer S. A new mechanism for amyloid-b induction of iNOS: vitamin D-VDR pathway disruption. J Alzheimers Dis. 2013;36(3):459–74.

    CAS  PubMed  Google Scholar 

  21. 21.

    Hur J et al. Regulatory effect of 25-hydroxyvitamin D3 on nitric oxide production in activated microglia. Korean J Physiol Pharmacolx. 2014;18(5):397–402.

    CAS  Article  Google Scholar 

  22. 22.

    Garcion E et al. 1,25-Dihydroxyvitamin D3 regulates the synthesis of gamma-glutamyl transpeptidase and glutathione levels in rat primary astrocytes. J Neurochem. 1999;73(2):859–66.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Shinpo K et al. Effect of 1,25-dihydroxyvitamin D3 on cultured mesencephalic dopaminergic neurons to the combined toxicity caused by L-buthionine sulfoximine and 1-methyl-4-phenylpyridine. J Neurosci Res. 2000;62(3):374–82.

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Lu’o’ng KV, Nguyen LT. The beneficial role of vitamin D in Alzheimer’s disease. Am J Alheimers Dis Other Demen. 2011;26(7):511–20.

    Article  Google Scholar 

  25. 25.

    Durk MR et al. 1,25-Dihydroxyvitamin D3 reduces cerebral amyloid-β accumulation and improves cognition in mouse models of Alzheimer’s disease. J Neurosci. 2014;34(21):7091–101.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Grimm MO et al. Impact of vitamin D on amyloid precursor protein processing and amyloid-β peptid degradation in Alzheimer’s disease. Neurodegener Dis. 2014;13:75–81.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Camu W et al. Vitamin D confers protection to motoneurons and is a prognostic factor of amyotrophic lateral sclerosis. Neurobiol Aging. 2014;35(5):1198–205.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Puchacz E et al. Vitamin D increases expression of the tyrosine hydroxylase gene in adrenal medullary cells. Brain Res Mol Brain Res. 1996;36:193–6.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Sanchez B et al. 1,25-Dihydroxyvitamin D3 administration to 6-hydroxydopamine-lesioned rats increases glial cell line-derived neurotrophic factor and partially restores tyrosine hydroxylase expression in substantia nigra and striatum. J Neurosci Res. 2009;87:723–32.

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Hollo A, Clemens Z, Lakatos P. Epilepsy and vitamin D. Int J Neurosci. 2014;124(6):387–93.

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Di Rosa M et al. Vitamin D3: a helpful immuno-modulator. Immunology. 2011;134:123–39.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  32. 32.

    Moro JR, Iwata M, von Andriano UH. Vitamin effects on the immune system, vitamins A and D take centre stage. Nat Rev Immunol. 2008;8:685–98.

    Article  CAS  Google Scholar 

  33. 33.

    Ferreira GB et al. 1,25-Dihydroxyvitamin D3 alters murine dendritic cell behaviour in vitro and in vivo. Diabetes Metab Res Rev. 2011;27:933–41.

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Farias AS et al. Vitamin D3 induces IDO(+) tolerogenic DCs and enhances treg, reducing the severity of EAE. CNS Neurosci Ther. 2013;19:269–77.

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Jeffery LE et al. Availability of 25-hydroxyvitamin D3 to APCs controls the balance between regulatory and inflammatory T cell responses. J Immunol. 2012;189:5155–64.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  36. 36.

    Lemire JM, Archer DC. 1,25-Dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Invest. 1991;87:1103–7.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  37. 37.••

    Kang SW et al. 1,25-Dihydroxyvitamin D3 promotes FOXP3 expression via binding to vitamin D response elements in its conserved noncoding sequence region. J Immunol. 2012;188:5276–82. This article provided the first evidence of direct effect of vitamin D on T lymphoctyes.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  38. 38.

    Chen S et al. Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol. 2007;179:1634–47.

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Won S et al. Vitamin D prevents hypoxia/reoxygenation-induced blood-brain barrier disruption via vitamin D receptor-mediated NF-kB signaling pathways. PLoS One. 2015;10(3):e0122821.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  40. 40.

    Grishkan IV et al. 1,25-Dihydroxyvitamin D3 selectively and reversibly impairs T helper-cell CNS localization. Proc Natl Acad Sci U S A. 2013;110(52):21101–6.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  41. 41.

    Smolders J et al. Expression of vitamin D receptor and metabolizing enzymes in multiple sclerosis-affected brain tissue. J Neuropathol Exp Neurol. 2013;72:91–105.

    CAS  PubMed  Article  Google Scholar 

  42. 42.

    Wergeland S et al. Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. PLoS One. 2011;6(10):e26262.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  43. 43.

    Nystad AE et al. Effect of high-dose 1,25-dihydroxyvitamin D3 on remyelination in the cuprizone model. APMIS. 2014;122(12):1178–86.

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    Hewer S et al. Vitamin D and multiple sclerosis. J Clin Neurosci. 2013;20(5):634–41.

    CAS  PubMed  Article  Google Scholar 

  45. 45.

    Hayes CE. Vitamin D: a natural inhibitor of multiple sclerosis. Proc Nutr Soc. 2000;59(4):531–5.

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Beretich BD, Beretich TM. Explaining multiple sclerosis prevalence by ultraviolet exposure: a geospatial analysis. Mult Scler. 2009;15(8):891–8.

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Lucas RM et al. Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology. 2011;76(6):520–48.

    Article  CAS  Google Scholar 

  48. 48.

    McDowell TY et al. Sun exposure, vitamin D, and age at disease onset in relapsing multiple sclerosis. Neuroepidemiology. 2011;36(1):39–45.

    PubMed  Article  Google Scholar 

  49. 49.

    Kampman MT, Brustad M. Vitamin D: a candidate for the environmental effect in multiple sclerosis—observations from Norway. Neuroepidemiology. 2008;30(3):140–6.

    PubMed  Article  Google Scholar 

  50. 50.

    Alonso A, Hernan MA. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology. 2008;71(2):129–35.

    PubMed Central  PubMed  Article  Google Scholar 

  51. 51.

    Duan S et al. Vitamin D status and the risk of multiple sclerosis: a systemic review and meta-analysis. Neurosci Lett. 2014;570:108–13.

    CAS  PubMed  Article  Google Scholar 

  52. 52.

    Munger KL et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006;296(23):2832–8.

    CAS  PubMed  Article  Google Scholar 

  53. 53.

    Mowry EM et al. Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol. 2010;67(5):618–24.

    CAS  PubMed  Google Scholar 

  54. 54.

    Runia TF et al. Lower serum vitamin D levels are associated with a higher relapse risk in multiple sclerosis. Neurology. 2012;79(3):261–6.

    CAS  PubMed  Article  Google Scholar 

  55. 55.

    Simpson S et al. Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol. 2010;68(2):193.203.

    PubMed  Google Scholar 

  56. 56.

    Van der Mei IA et al. Vitamin D levels in people with multiple sclerosis and community controls in Tasmani. Aust J Neurol. 2007;254(5):581–90.

    Article  CAS  Google Scholar 

  57. 57.

    Smolders J et al. Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis. Mult Scler. 2008;14(9):1220–4.

    CAS  PubMed  Article  Google Scholar 

  58. 58.••

    Mowry EM et al. Vitamin D status predicts new brain MRI activity in multiple sclerosis. Ann Neurol. 2012;72(2):234–40. This study demonstrated that serum vitamin D levels are inversely associated with the development of new T2-weighted lesions on MRI in patients with MS.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  59. 59.

    Weinstock-Guttman B et al. Vitamin D metabolites are associated with clinical and MRI outcomes in multiple sclerosis patients. J Neurol Neurosurg Psychiatry. 2011;82(2):189–95.

    PubMed  Article  Google Scholar 

  60. 60.

    Stewart N et al. Interferon- β and serum 25-hydroxyvitamin D interact to modulate relapse risk in MS. Neurology. 2012;79(3):254–60.

    CAS  PubMed  Article  Google Scholar 

  61. 61.

    Ascherio A, Munger KL, Simon KC. Vitamin D and multiple sclerosis. Lancet Neurol. 2010;9(6):599–612.

    PubMed  Article  Google Scholar 

  62. 62.

    Ganesh A et al. The case for vitamin D supplementation in multiple sclerosis. Mult Scler Relat Disord. 2013;2(4):281–306.

    PubMed  Article  Google Scholar 

  63. 63.

    Burton JM et al. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology. 2010;74(23):1852–9.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  64. 64.••

    Soilu-Hanninen M et al. A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon β-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2012;83(5):565–71. This double-blind, placebo-controlled, randomized study demonstrated that patients with MS receiving vitamin D supplementation had fewer new T2-weighted lesions and a significantly lower number of T1 enhancing lesions as well as a tendency for reduced disability accumulation and improved timed tandem walk compared to controls not receiving vitamin D supplementation.

    PubMed  Article  Google Scholar 

  65. 65.

    Wingerchuk DM et al. A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2005;76(9):1294–6.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  66. 66.

    Pierrot-Deseilligny C et al. Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation. Ther Adv Neurol Disord. 2012;5(4):187–98.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  67. 67.

    James E et al. The effect of vitamin D-related interventions on multiple sclerosis relapses: a meta-analysis. Mult Scler. 2013;19(12):1571–9.

    PubMed  Article  CAS  Google Scholar 

  68. 68.

    Mosayebi G et al. Therapeutic effect of vitamin D3 in multiple sclerosis patients. Immunol Investig. 2011;40(6):627–39.

    CAS  Article  Google Scholar 

  69. 69.

    Stein MS et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology. 2011;77(17):1611–8.

    CAS  PubMed  Article  Google Scholar 

  70. 70.

    Kampman MT et al. Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial. Mult Scler. 2012;18(8):1144–51.

    PubMed  Article  CAS  Google Scholar 

  71. 71.

    Shaygannejad V et al. Effects of adjunct low-dose vitamin D on relapsing-remitting multiple sclerosis progression: preliminary findings of a randomized placebo-controlled trial. Mult Scler Int. 2012;2012:452541.

    PubMed Central  PubMed  Google Scholar 

  72. 72.

    Pozuelo-Moyano B et al. A systematic review of randomized, double-blind, placebo-controlled trials examining the clinical efficacy of vitamin D in multiple sclerosis. Neuroepidemiology. 2013;40(3):147–53.

    PubMed Central  PubMed  Article  Google Scholar 

  73. 73.

    Mowry EM. Vitamin D: evidence for its role as a prognostic factor in multiple sclerosis. J Neurol Sci. 2011;311(1-2):19–22.

    CAS  PubMed  Article  Google Scholar 

  74. 74.

    Slinin Y et al. 25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men. Neurology. 2010;74:33–41.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  75. 75.

    Annweiler C et al. Hypovitaminosis D and executive dysfunction in older adults with memory complaint: a memory clinic-based study. Dement Geriatr Cogn Disord. 2013;37:286–93.

    PubMed  Article  CAS  Google Scholar 

  76. 76.

    Brouwer-Brolsma EM et al. Serum 25-hydroxyvitamin D is associated with cognitive executive function in Dutch prefrail and frail elderly: a cross-sectional study exploring the associations of 25-hydroxyvitamin D with glucose metabolism, cognitive performance and depression. J Am Med Dir Assoc. 2013;14(852):e859–817.

    Google Scholar 

  77. 77.

    Annweiler C et al. Serum vitamin D deficiency as a predictor of incident non-Alzheimer dementias: a 7-year longitudinal study. Dement Geriatr Cogn Disord. 2011;32:273–8.

    CAS  PubMed  Article  Google Scholar 

  78. 78.

    Balion C et al. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology. 2012;79:1397–405.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  79. 79.

    Annweiler C, Llewellyn DJ, Beauchet O. Low serum vitamin D concentrations in Alzheimer's disease: a systematic review and meta-analysis. J Alzheimers Dis. 2013;33:659–74.

    CAS  PubMed  Google Scholar 

  80. 80.

    Chei CL et al. Vitamin D levels and cognition in elderly adults in China. J Am Geriatr Soc. 2014;62:2125–9.

    PubMed Central  PubMed  Article  Google Scholar 

  81. 81.••

    Littlejohns TJ et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology. 2014;83:920–8. This large prospective cohort study showed that hypovitaminosis D resulted in a markedly increased risk of incident Alzheimer’s disease and all-cause dementia.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  82. 82.

    Berridge MJ. Calcium regulation of neural rhythms, memory and Alzheimer's disease. J Physiol. 2014;592:281–93.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  83. 83.

    Moon M et al. Vitamin D-binding protein interacts with Abeta and suppresses Abeta-mediated pathology. Cell Death Differ. 2013;20:630–8.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  84. 84.

    Morley JE, Farr SA. The role of amyloid-beta in the regulation of memory. Biochem Pharmacol. 2014;88:479–85.

    CAS  PubMed  Article  Google Scholar 

  85. 85.

    Bishnoi RJ, Palmer RF, Royall DR. Vitamin D binding protein as a serum biomarker of Alzheimer's disease. J Alzheimers Dis. 2015;43:37–45.

    CAS  PubMed  Google Scholar 

  86. 86.

    Johansson P et al. Cerebrospinal fluid (CSF) 25-hydroxyvitamin D concentration and CSF acetylcholinesterase activity are reduced in patients with Alzheimer's disease. PLoS One. 2013;8:e81989.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  87. 87.

    Muenchhoff J et al. Plasma protein profiling of mild cognitive impairment and Alzheimer's disease across two independent cohorts. J Alzheimers Dis. 2015;43:1355–73.

    CAS  PubMed  Google Scholar 

  88. 88.

    Laczmanski L et al. Vitamin D receptor gene polymorphisms in Alzheimer's disease patients. Exp Gerontol. 2015;69:142–7.

    CAS  PubMed  Article  Google Scholar 

  89. 89.

    Annweiler C et al. Cognitive effects of vitamin D supplementation in older outpatients visiting a memory clinic: a pre-post study. J Am Geriatr Soc. 2012;60:793–5.

    PubMed  Article  Google Scholar 

  90. 90.

    Stein MS et al. A randomized controlled trial of high-dose vitamin D2 followed by intranasal insulin in Alzheimer's disease. J Alzheimers Dis. 2011;26:477–84.

    CAS  PubMed  Article  Google Scholar 

  91. 91.

    Przybelski R et al. Rapid correction of low vitamin D status in nursing home residents. Osteoporos Int. 2008;19:1621–8.

    CAS  PubMed  Article  Google Scholar 

  92. 92.

    Annweiler C et al. ‘Vitamin D and cognition in older adults’: updated international recommendations. J Intern Med. 2014;277:45–57.

    PubMed  Article  CAS  Google Scholar 

  93. 93.

    Ding H et al. Unrecognized vitamin D3 deficiency is common in Parkinson disease: Harvard Biomarker Study. Neurology. 2013;81:1531–7.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  94. 94.

    Peterson AL, Mancini M, Horak FB. The relationship between balance control and vitamin D in Parkinson's disease—a pilot study. Mov Disord. 2013;28:1133–7.

    PubMed  Article  Google Scholar 

  95. 95.

    Evatt ML et al. Prevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer disease. Arch Neurol. 2008;65:1348–52.

    PubMed Central  PubMed  Article  Google Scholar 

  96. 96.

    Suzuki M et al. 25-Hydroxyvitamin D, vitamin D receptor gene polymorphisms, and severity of Parkinson's disease. Mov Disord. 2012;27:264–71.

    CAS  PubMed  Article  Google Scholar 

  97. 97.

    Sato Y, Honda Y, Iwamoto J. Risedronate and ergocalciferol prevent hip fracture in elderly men with Parkinson disease. Neurology. 2007;68:911–5.

    CAS  PubMed  Article  Google Scholar 

  98. 98.

    Smith MP et al. Calcitriol protection against dopamine loss induced by intracerebroventricular administration of 6-hydroxydopamine. Neurochem Res. 2006;31:533–9.

    CAS  PubMed  Article  Google Scholar 

  99. 99.

    Kim JS et al. 1alpha,25-Dihydroxyvitamin D(3) Protects dopaminergic neurons in rodent models of Parkinson’s disease through inhibition of microglial activation. J Clin Neurol. 2006;2:252–7.

  100. 100.

    Wang JY et al. Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats. Brain Res. 2001;904:67–75.

    CAS  PubMed  Article  Google Scholar 

  101. 101.

    Butler MW et al. Vitamin D receptor gene as a candidate gene for Parkinson disease. Ann Hum Genet. 2011;75:201–10.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  102. 102.

    Torok R et al. Association of vitamin D receptor gene polymorphisms and Parkinson's disease in Hungarians. Neurosci Lett. 2013;551:70–4.

    CAS  PubMed  Article  Google Scholar 

  103. 103.

    Lee YH, Kim JH, Song GG. Vitamin D receptor polymorphisms and susceptibility to Parkinson's disease and Alzheimer's disease: a meta-analysis. Neurol Sci. 2014;35:1947–53.

    PubMed  Article  Google Scholar 

  104. 104.

    Zhang ZT et al. Association between vitamin D receptor gene polymorphisms and susceptibility to Parkinson's disease: a meta-analysis. Neurosci Lett. 2014;578:122–7.

    CAS  PubMed  Article  Google Scholar 

  105. 105.••

    Camu W et al. Vitamin D confers protection to motoneurons and is a prognostic factor of amyotrophic lateral sclerosis. Neurobiol Aging. 2014;35:1198–205. This study showed that lower levels of vitamin D correlated with faster functional decline in ALS patients, even after excluding non-ambulatory patients.

    CAS  PubMed  Article  Google Scholar 

  106. 106.

    Blasco H et al. Vitamin D is not a protective factor in ALS. CNS Neurosci Ther. 2015;21(8):651–6.

    CAS  PubMed  Article  Google Scholar 

  107. 107.

    Karam C et al. Vitamin D deficiency and its supplementation in patients with amyotrophic lateral sclerosis. J Clin Neurosci. 2013;20:1550–3.

    CAS  PubMed  Article  Google Scholar 

  108. 108.

    Wang L et al. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ Cardiovasc Qual Outcomes. 2012;5:819–29.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  109. 109.

    Schneider AL et al. Vitamin D, vitamin D binding protein gene polymorphisms, race and risk of incident stroke: the Atherosclerosis Risk in Communities (ARIC) study. Eur J Neurol. 2015;22:1220–7.

    PubMed Central  CAS  PubMed  Article  Google Scholar 

  110. 110.

    Brondum-Jacobsen P et al. 25-Hydroxyvitamin D and symptomatic ischemic stroke: an original study and meta-analysis. Ann Neurol. 2013;73:38–47.

    CAS  PubMed  Article  Google Scholar 

  111. 111.

    Chowdhury R et al. Circulating vitamin D, calcium and risk of cerebrovascular disease: a systematic review and meta-analysis. Eur J Epidemiol. 2012;27:581–91.

    CAS  PubMed  Article  Google Scholar 

  112. 112.

    Welles CC et al. Vitamin D deficiency and cardiovascular events in patients with coronary heart disease: data from the heart and soul Study. Am J Epidemiol. 2014;179:1279–87.

    PubMed Central  PubMed  Article  Google Scholar 

  113. 113.

    Herrmann M et al. Serum 25-hydroxyvitamin D: a predictor of macrovascular and microvascular complications in patients with type 2 diabetes. Diabetes Care. 2015;38:521–8.

    CAS  PubMed  Article  Google Scholar 

  114. 114.

    Chung PW et al. 25-Hydroxyvitamin D status is associated with chronic cerebral small vessel disease. Stroke. 2015;46:248–51.

    CAS  PubMed  Article  Google Scholar 

  115. 115.

    Michos ED et al. Vitamin D and subclinical cerebrovascular disease: the atherosclerosis risk in communities brain magnetic resonance imaging study. JAMA Neurol. 2014;71:863–71.

    PubMed Central  PubMed  Article  Google Scholar 

  116. 116.

    Yalbuzdag SA et al. Is 25(OH)D associated with cognitive impairment and functional improvement in stroke? A retrospective clinical study. J Stroke Cerebrovasc Dis. 2015;24:1479–86.

    PubMed  Article  Google Scholar 

  117. 117.

    Han B et al. Low serum levels of vitamin D are associated with post-stroke depression. Eur J Neurol. 2015;22(9):1269–74.

    CAS  PubMed  Article  Google Scholar 

  118. 118.

    Turetsky A, Goddeau Jr RP, Henninger N. Low serum vitamin D is independently associated with larger lesion volumes after ischemic stroke. J Stroke Cerebrovasc Dis. 2015;24:1555–63.

    PubMed  Article  Google Scholar 

  119. 119.

    Daubail B et al. Association between serum concentration of vitamin D and 1-year mortality in stroke patients. Cerebrovasc Dis. 2014;37:364–7.

    CAS  PubMed  Article  Google Scholar 

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Conflict of Interest

Anusha K. Yeshokumar and Deanna Saylor declare that they have no conflict of interest.

Michael D. Kornberg reports grants from NINDS and from National Multiple Sclerosis Society-American Academy of Neurology.

Ellen M. Mowry reports grants from Biogen Idec and received free medication for a clinical trial from Teva Neuroscience, and Dr. Mowry is PI of a multicenter randomized controlled trial of vitamin D supplementation in people with MS (sponsored by the National MS Society). She is site PI for a clinical trial sponsored by Sun Pharma.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Correspondence to Anusha K. Yeshokumar MD.

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This article is part of the Topical Collection on Neurologic Manifestations of Systemic Disease

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Yeshokumar, A.K., Saylor, D., Kornberg, M.D. et al. Evidence for the Importance of Vitamin D Status in Neurologic Conditions. Curr Treat Options Neurol 17, 51 (2015). https://doi.org/10.1007/s11940-015-0380-3

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Keywords

  • Vitamin D
  • Central nervous system
  • Multiple sclerosis
  • Alzheimer’s disease
  • Parkinson’s disease
  • Amyotrophic lateral sclerosis
  • Stroke