Evidence for the Importance of Vitamin D Status in Neurologic Conditions

  • Anusha K. YeshokumarEmail author
  • Deanna Saylor
  • Michael D. Kornberg
  • Ellen M. Mowry
Neurologic Manifestations of Systemic Disease (A Pruitt, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Neurologic Manifestations of Systemic Disease

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.


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


Compliance with Ethical Standards

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.

Human and Animal Rights and Informed Consent

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

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.CrossRefGoogle Scholar
  2. 2.
    Falkenstein E et al. Multiple actions of steroid hormones—a focus on rapid, nongenomic effects. Pharmacol Rev. 2000;52:513–56.PubMedGoogle Scholar
  3. 3.
    Khanal R, Nemere I. Membrane receptors for vitamin D metabolites. Crit Rev Eukaryot Gene Expr. 2007;17:31–47.PubMedCrossRefGoogle 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.CrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  8. 8.
    Eyles D et al. Vitamin D3 and brain development. Neuroscience. 2003;118:641–53.PubMedCrossRefGoogle Scholar
  9. 9.
    Feron F et al. Developmental vitamin D3 deficiency alters the adult rat brain. Brain Res Bull. 2005;65:141–8.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedGoogle 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.CrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.CrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  30. 30.
    Hollo A, Clemens Z, Lakatos P. Epilepsy and vitamin D. Int J Neurosci. 2014;124(6):387–93.PubMedCrossRefGoogle Scholar
  31. 31.
    Di Rosa M et al. Vitamin D3: a helpful immuno-modulator. Immunology. 2011;134:123–39.PubMedCentralPubMedCrossRefGoogle 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.CrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  42. 42.
    Wergeland S et al. Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. PLoS One. 2011;6(10):e26262.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  44. 44.
    Hewer S et al. Vitamin D and multiple sclerosis. J Clin Neurosci. 2013;20(5):634–41.PubMedCrossRefGoogle Scholar
  45. 45.
    Hayes CE. Vitamin D: a natural inhibitor of multiple sclerosis. Proc Nutr Soc. 2000;59(4):531–5.PubMedCrossRefGoogle Scholar
  46. 46.
    Beretich BD, Beretich TM. Explaining multiple sclerosis prevalence by ultraviolet exposure: a geospatial analysis. Mult Scler. 2009;15(8):891–8.PubMedCrossRefGoogle 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.CrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  50. 50.
    Alonso A, Hernan MA. Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology. 2008;71(2):129–35.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  52. 52.
    Munger KL et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006;296(23):2832–8.PubMedCrossRefGoogle 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.PubMedGoogle 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.PubMedCrossRefGoogle 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.PubMedGoogle 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.CrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  61. 61.
    Ascherio A, Munger KL, Simon KC. Vitamin D and multiple sclerosis. Lancet Neurol. 2010;9(6):599–612.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  68. 68.
    Mosayebi G et al. Therapeutic effect of vitamin D3 in multiple sclerosis patients. Immunol Investig. 2011;40(6):627–39.CrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCentralPubMedGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  74. 74.
    Slinin Y et al. 25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men. Neurology. 2010;74:33–41.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  78. 78.
    Balion C et al. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology. 2012;79:1397–405.PubMedCentralPubMedCrossRefGoogle 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.PubMedGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Berridge MJ. Calcium regulation of neural rhythms, memory and Alzheimer's disease. J Physiol. 2014;592:281–93.PubMedCentralPubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    Morley JE, Farr SA. The role of amyloid-beta in the regulation of memory. Biochem Pharmacol. 2014;88:479–85.PubMedCrossRefGoogle 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.PubMedGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedGoogle Scholar
  88. 88.
    Laczmanski L et al. Vitamin D receptor gene polymorphisms in Alzheimer's disease patients. Exp Gerontol. 2015;69:142–7.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  91. 91.
    Przybelski R et al. Rapid correction of low vitamin D status in nursing home residents. Osteoporos Int. 2008;19:1621–8.PubMedCrossRefGoogle Scholar
  92. 92.
    Annweiler C et al. ‘Vitamin D and cognition in older adults’: updated international recommendations. J Intern Med. 2014;277:45–57.PubMedCrossRefGoogle Scholar
  93. 93.
    Ding H et al. Unrecognized vitamin D3 deficiency is common in Parkinson disease: Harvard Biomarker Study. Neurology. 2013;81:1531–7.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.Google Scholar
  100. 100.
    Wang JY et al. Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats. Brain Res. 2001;904:67–75.PubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  106. 106.
    Blasco H et al. Vitamin D is not a protective factor in ALS. CNS Neurosci Ther. 2015;21(8):651–6.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  114. 114.
    Chung PW et al. 25-Hydroxyvitamin D status is associated with chronic cerebral small vessel disease. Stroke. 2015;46:248–51.PubMedCrossRefGoogle 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.PubMedCentralPubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Anusha K. Yeshokumar
    • 1
    Email author
  • Deanna Saylor
    • 1
  • Michael D. Kornberg
    • 1
  • Ellen M. Mowry
    • 1
  1. 1.Department of NeurologyJohns Hopkins UniversityBaltimoreUSA

Personalised recommendations