Are the protective benefits of vitamin D in neurodegenerative disease dependent on route of administration? A systematic review

References

• Przedborski S, Vila M, Jackson-Lewis V. Neurodegeneration: what is it and where are we? J Clin Invest 2003;111(1):3–10.
   PubMed Web of Science ®Google Scholar
• Koduah P, Paul F, Dorr JM. Vitamin D in the prevention, prediction and treatment of neurodegenerative and neuroinflammatory diseases. EPMA J 2017;8(4):313–25.
   PubMed Web of Science ®Google Scholar
• Annweiler C, Llewellyn DJ, Beauchet O. Low serum vitamin D concentrations in Alzheimer’s disease: A systematic review and meta-analysis. J Alzheimer’s Dis 2013;33(3):659–74.
   PubMed Web of Science ®Google Scholar
• Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. J Am Med Assoc 2006;296(23):2832–8.
   PubMed Web of Science ®Google Scholar
• Annweiler C, Rolland Y, Schott A, Blain H, Vellas B, Beauchet O. Serum vitamin D deficiency as a predictor of incident non-Alzheimer dementias: A 7-year longitudinal study. Dement Geriatr Cogn Disord 2011;32(4):273–8.
   PubMed Web of Science ®Google Scholar
• Duan S, Lv Z, Fan X, Wang L, Han F, Wang H, et al. Vitamin D status and the risk of multiple sclerosis: a systematic review and meta-analysis. Neurosci Lett 2014;570:108–13.
   PubMed Web of Science ®Google Scholar
• Landel V, Millet P, Baranger K, Loriod B, Feron F. Vitamin D interacts with Esr1 and Igf1 to regulate molecular pathways relevant to Alzheimer’s disease. Mol Neurodegen 2016;11(1):22.
   PubMedGoogle Scholar
• Shen L, Ji HF. Associations between vitamin D status, supplementation, outdoor work and risk of Parkinson’s disease: A meta-analysis assessment. Nutrients 2015;7(6):4817–27.
   PubMed Web of Science ®Google Scholar
• Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc 2011;86(1):50–60.
   PubMed Web of Science ®Google Scholar
• Bikle Daniel D. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol . 2014;21(3):319–29.
   PubMedGoogle Scholar
• Zhang R, Naughton DP. Vitamin D in health and disease: current perspectives. Nutr J. 2010;9(1):13.
   PubMedGoogle Scholar
• Anderson F. Vitamin D for older people: how much, for whom and-above all-why? Age Ageing. 2005;34(5):425–6.
   PubMed Web of Science ®Google Scholar
• van Schoor N, Lips P. Global overview of vitamin D status. Endocrinol Metab Clin N Am 2017;46(4):845–70.
   PubMed Web of Science ®Google Scholar
• Crowe FL, Steur M, Allen NE, Appleby PN, Travis RC, Key TJ. Plasma concentrations of 25-hydroxyvitamin D in meat eaters, fish eaters, vegetarians and vegans: results from the EPIC-Oxford study. Public Health Nutr 2011;14(2):340–6.
   PubMed Web of Science ®Google Scholar
• Japelt RB, Jakobsen J. Vitamin D in plants: a review of occurrence, analysis, and biosynthesis. Front Plant Sci 2013;4:136.
   PubMed Web of Science ®Google Scholar
• Rapuri PB, Gallagher JC, Haynatzki G. Effect of vitamins D2 and D3 supplement use on serum 25OHD concentration in elderly women in summer and winter. Calcified Tissue Int 2004;74(2):150–6.
   PubMed Web of Science ®Google Scholar
• Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr 2006;84(4):694–7.
   PubMed Web of Science ®Google Scholar
• Armas LAG, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 2004;89(11):5387–91.
   PubMed Web of Science ®Google Scholar
• Marx SJ, Jones G, Weinstein RS. Differences in mineral metabolism among nonhuman primates receiving diets with only vitamin D3 or only vitamin D2. J Clin Endocrinol Metab. 1989;69(6):1282–90.
   PubMed Web of Science ®Google Scholar
• Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr 1998;68(4):854–8.
   PubMed Web of Science ®Google Scholar
• Horst RL, Reinhardt TA, Ramberg CF. 24-Hydroxylation of 1, 25-dihydroxyergocalciferol. An unambiguous deactivation process. J Biol Chem 1986;261(20):9250–6.
   PubMed Web of Science ®Google Scholar
• Holick MF. Vitamin D: A D-lightful solution for health. J Invest Med 2011;59(6):872–80.
   PubMed Web of Science ®Google Scholar
• Fernandes de Abreu DA, Eyles D, Féron F. Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases. Psychoneuroendocrinology 2009;34(SUPPL. 1):S265-SS77.
   PubMedGoogle Scholar
• Mpandzou G, Ben Haddou E, Regragui W, Benomar A, Yahyaoui M. Vitamin D deficiency and its role in neurological conditions: A review. Rev Neurol (Paris) 2016;172(2):109–22.
   PubMed Web of Science ®Google Scholar
• Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D. New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab TEM. 2002;13(3):100–5.
   PubMed Web of Science ®Google Scholar
• Neveu I, Naveilhan P, Baudet C, Brachet P, Metsis M. 1,25-dihydroxyvitamin d3 regulates NT-3, NT-4 but not BDNF mRNA in astrocytes. Neuroreport 1994;6(1):124–6.
   PubMed Web of Science ®Google Scholar
• Naveilhan P, Neveu I, Wion D, Brachet P. 1,25-Dihydroxyvitamin d3, an inducer of glial cell line-derived neurotrophic factor. Neuroreport. 1996;7(13):2171–5.
   PubMed Web of Science ®Google Scholar
• Musiol IM, Feldman D. 1,25-dihydroxyvitamin d3 induction of nerve growth factor in L929 mouse fibroblasts: effect of vitamin D receptor regulation and potency of vitamin D3 analogs. Endocrinology 1997;138(1):12–18.
   PubMed Web of Science ®Google Scholar
• Masoumi A, Goldenson B, Ghirmai S, Avagyan H, Zaghi J, Abel K, et al. 1alpha,25-dihydroxyvitamin d3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimer’s disease patients. J Alzheimer’s Dis JAD. 2009;17(3):703–17.
   PubMed Web of Science ®Google Scholar
• Grimm MOW, Thiel A, Lauer AA, Winkler J, Lehmann J, Regner L, et al. Vitamin D and Its analogues decrease amyloid-beta (abeta) formation and increase abeta-degradation. Int J Mol Sci 2017;18(12):e2764.
   Web of Science ®Google Scholar
• Dankers W, Colin EM, van Hamburg JP, Lubberts E. Vitamin D in autoimmunity: molecular mechanisms and therapeutic potential. Front Immunol 2016;7:697.
   PubMed Web of Science ®Google Scholar
• Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients 2013;5(7):2502–21.
   PubMed Web of Science ®Google Scholar
• Zeitelhofer M, Adzemovic MZ, Gomez-Cabrero D, Bergman P, Hochmeister S, N’Diaye M, et al. Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 2017;114(9):E1678-E1e87.
   Google Scholar
• Wang JY, Wu JN, Cherng TL, Hoffer BJ, Chen HH, Borlongan CV, et al. Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats. Brain Res 2001;904(1):67–75.
   PubMed Web of Science ®Google Scholar
• Smith MP, Fletcher-Turner A, Yurek DM, Cass WA. Calcitriol protection against dopamine loss induced by intracerebroventricular administration of 6-hydroxydopamine. Neurochem Res 2006;31(4):533–9.
   PubMed Web of Science ®Google Scholar
• Sanchez B, Relova JL, Gallego R, Ben-Batalla I, Perez-Fernandez R. 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(3):723–32.
   PubMed Web of Science ®Google Scholar
• Grant WB. The role of geographical ecological studies in identifying diseases linked to UVB exposure and/or vitamin D. Dermatoendocrinol 2016;8(1):e1137400-1-23.
   Web of Science ®Google Scholar
• Kragt JJ, van Amerongen BM, Killestein J, Dijkstra CD, Uitdehaag BMJ, Polman CH, et al. Higher levels of 25-hydroxyvitamin D are associated with a lower incidence of multiple sclerosis only in women. Mult Scler 2009;15(1):9–15.
   PubMed Web of Science ®Google Scholar
• Mosayebi G, Ghazavi A, Ghasami K, Jand Y, Kokhaei P. Therapeutic effect of vitamin D3 in multiple sclerosis patients. Immunol Invest. 2011;40(6):627–39.
   PubMed Web of Science ®Google Scholar
• Suzuki M, Yoshioka M, Hashimoto M, Murakami M, Noya M, Takahashi D, et al. Randomized, double-blind, placebo-controlled trial of vitamin D supplementation in Parkinson disease. Am J Clin Nutr 2013;97(5):1004–13.
   PubMed Web of Science ®Google Scholar
• Zheng C, He L, Liu L, Zhu J, Jin T. The efficacy of vitamin D in multiple sclerosis: A meta-analysis. Mult Scler Relat Disord 2018;23:56–61.
   PubMed Web of Science ®Google Scholar
• Cock PJ, Antao T, Chang JT, Chapman BA, Cox CJ, Dalke A, et al. Biopython: freely available python tools for computational molecular biology and bioinformatics. Bioinformatics 2009;25(11):1422–3.
   PubMed Web of Science ®Google Scholar
• Achiron A, Givon U, Magalashvili D, Dolev M, Liraz Zaltzman S, Kalron A, et al. Effect of alfacalcidol on multiple sclerosis-related fatigue: A randomized, double-blind placebo-controlled study. Mult Scler 2015;21(6):767–75.
   PubMed Web of Science ®Google Scholar
• McInnes MDF, Moher D, Thombs BD, McGrath TA, Bossuyt PM, Clifford T, et al. Preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies: The PRISMA-DTA statement. Jama 2018;319(4):388–96.
   PubMed Web of Science ®Google Scholar
• Adzemovic MZ, Zeitelhofer M, Hochmeister S, Gustafsson SA, Jagodic M. Efficacy of vitamin D in treating multiple sclerosis-like neuroinflammation depends on developmental stage. Exp Neurol 2013;249:39–48.
   PubMed Web of Science ®Google Scholar
• Becklund BR, Severson KS, Vang SV, DeLuca HF. UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production. Proc Natl Acad Sci USA 2010;107(14):6418–23.
   Google Scholar
• Farias AS, Spagnol GS, Bordeaux-Rego P, Oliveira COF, Fontana AGM, de Paula RFO, et al. Vitamin D3 induces IDO+ tolerogenic DCs and enhances treg, reducing the severity of EAE. CNS Neurosci Ther 2013;19(4):269–77.
   PubMed Web of Science ®Google Scholar
• Garcion E, Sindji L, Nataf S, Brachet P, Darcy F, Montero-Menei CN. Treatment of experimental autoimmune encephalomyelitis in rat by 1,25-dihydroxyvitamin D3 lead to early effects within the central nervous system. Acta Neuropathol 2003;105(5):438–48.
   PubMed Web of Science ®Google Scholar
• Nashold FE, Miller DJ, Hayes CE. 1,25-Dihydroxyvitamin d3 treatment decreases macrophage accumulation in the CNS of mice with experimental autoimmune encephalomyelitis. J Neuroimmunol 2000;103(2):171–9.
   PubMed Web of Science ®Google Scholar
• Nashold FE, Nelson CD, Brown LM, Hayes CE. One calcitriol dose transiently increases helios + FoxP3+ T cells and ameliorates autoimmune demyelinating disease. J Neuroimmunol 2013;263(1–2):64–74.
   PubMed Web of Science ®Google Scholar
• Nataf S, Garcion E, Darcy F, Chabannes D, Muller JY, Brachet P. 1,25 dihydroxyvitamin D3 exerts regional effects in the central nervous system during experimental allergic encephalomyelitis. J Neuropathol Exp Neurol 1996;55(8):904–14.
   PubMed Web of Science ®Google Scholar
• Pedersen LB, Nashold FE, Spach KM, Hayes CE. 1,25-Dihydroxyvitamin d3 reverses experimental autoimmune encephalomyelitis by inhibiting chemokine synthesis and monocyte trafficking. J Neurosci Res 2007;85(11):2480–90.
   PubMed Web of Science ®Google Scholar
• Sloka S, Zhornitsky S, Silva C, Metz LM, Yong VW. 1,25-Dihydroxyvitamin d3 protects against immune-mediated killing of neurons in culture and in experimental autoimmune encephalomyelitis. PloS One. 2015;10(12):11.
   Web of Science ®Google Scholar
• Soleimani M, Jameie SB, Mehdizadeh M, Keradi M, Masoumipoor M, Mehrabi S. Vitamin D3 influence the Th1/Th2 ratio in C57BL/6 induced model of experimental autoimmune encephalomyelitis. Iran J Basic Med Sci 2014;17(10):785–92.
   PubMed Web of Science ®Google Scholar
• Spach KM, Hayes CE. Vitamin D3 confers protection from autoimmune encephalomyelitis only in female mice. J Immunol 2005;175(6):4119–26.
   PubMed Web of Science ®Google Scholar
• Spach KM, Nashold FE, Dittel BN, Hayes CE. IL-10 signaling is essential for 1,25-dihydroxyvitamin D 3-mediated inhibition of experimental autoimmune encephalomyelitis. J Immunol 2006;177(9):6030–7.
   PubMed Web of Science ®Google Scholar
• Wang Y, Marling SJ, Beaver EF, Severson KS, Deluca HF. UV light selectively inhibits spinal cord inflammation and demyelination in experimental autoimmune encephalomyelitis. Arch Biochem Biophys 2015;567:75–82.
   PubMed Web of Science ®Google Scholar
• Wang Y, Marling SJ, Zhu JG, Severson KS, DeLuca HF. Development of experimental autoimmune encephalomyelitis (EAE) in mice requires vitamin D and the vitamin D receptor. Proc Natl Acad Sci USA 2012;109(22):8501–4.
   PubMed Web of Science ®Google Scholar
• Wang YP, Marling SJ, McKnight SM, Danielson AL, Severson KS, Deluca HF. Suppression of experimental autoimmune encephalomyelitis by 300-315 nm ultraviolet light. Arch Biochem Biophys 2013;536(1):81–6.
   PubMed Web of Science ®Google Scholar
• Tarbali S, Khezri S. Vitamin D3 attenuates oxidative stress and cognitive deficits in a model of toxic demyelination. Iran J Basic Med Sci 2016;19(1):80–8.
   PubMed Web of Science ®Google Scholar
• Van Der Mei IAF, Ponsonby AL, Dwyer T, Blizzard L, Simmons R, Taylor BV, et al. Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study. Br Med J 2003;327(7410):316–20.
   PubMed Web of Science ®Google Scholar
• Kampman MT, Wilsgaard T, Mellgren SI. Outdoor activities and diet in childhood and adolescence relate to MS risk above the Arctic circle. J Neurol 2007;254(4):471–7.
   PubMed Web of Science ®Google Scholar
• Islam T, Gauderman WJ, Cozen W, Mack TM. Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins. Neurology 2007;69(4):381–8.
   PubMed Web of Science ®Google Scholar
• Espinosa-Ramirez G, Ordonez G, Flores-Rivera J, Sotelo J. Sunlight exposure and multiple sclerosis in a tropical country. Neurol Res 2014;36(7):647–50.
   PubMed Web of Science ®Google Scholar
• Dalmay F, Bhalla D, Nicoletti A, Cabrera-Gomez JA, Cabre P, Ruiz F, et al. Multiple sclerosis and solar exposure before the age of 15 years: case-control study in Cuba, Martinique and sicily. Mult Scler 2010;16(8):899–908.
   PubMedGoogle Scholar
• Bjornevik K, Riise T, Casetta I, Drulovic J, Granieri E, Holmoy T, et al. Sun exposure and multiple sclerosis risk in Norway and Italy: The EnvIMS study. Mult Scler. 2014;20(8):1042–9.
   PubMed Web of Science ®Google Scholar
• Baarnhielm M, Hedstrom A, Kockum I, Sundqvist E, Gustafsson S, Hillert J, et al. Sunlight is associated with decreased multiple sclerosis risk: No interaction with human leukocyte antigen-DRB1*15. Eur J Neurol 2012;19(7):955–62.
   PubMed Web of Science ®Google Scholar
• McDowell TY, Amr S, Culpepper WJ, Langenberg P, Royal W, Bever C, et al. Sun exposure, vitamin D and age at disease onset in relapsing multiple sclerosis. Neuroepidemiology 2011;36(1):39–45.
   PubMed Web of Science ®Google Scholar
• McDowell TY, Amr S, Culpepper WJ, Langenberg P, Royal W, Bever C, et al. Sun exposure, vitamin D intake and progression to disability among veterans with progressive multiple sclerosis. Neuroepidemiology 2011;37(1):52–7.
   PubMed Web of Science ®Google Scholar
• Jelinek GA, Marck CH, Weiland TJ, Pereira N, van der Meer DM, Hadgkiss EJ. Latitude, sun exposure and vitamin D supplementation: associations with quality of life and disease outcomes in a large international cohort of people with multiple sclerosis. BMC Neurol 2015;15. ArtID 132. 2015;15:6.
   PubMed Web of Science ®Google Scholar
• D’Hooghe M B, Haentjens P, Nagels G, Garmyn M, De Keyser J. Sunlight exposure and sun sensitivity associated with disability progression in multiple sclerosis. Mult Scler 2012;18(4):451–9.
   PubMed Web of Science ®Google Scholar
• Van Der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Taylor BV, Kilpatrick T, et al. Vitamin D levels in people with multiple sclerosis and community controls in tasmania, Australia. J Neurol 2007;254(5):581–90.
   PubMed Web of Science ®Google Scholar
• Mandia D, Ferraro OE, Nosari G, Montomoli C, Zardini E, Bergamaschi R. Environmental factors and multiple sclerosis severity: a descriptive study. Int J Environ Res Public Health 2014;11(6):6417–32.
   PubMed Web of Science ®Google Scholar
• Lucas RM, Ponsonby AL, Dear K, Valery PC, Pender MP, Taylor BV, et al. Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology 2011;76(6):540–8.
   PubMed Web of Science ®Google Scholar
• Hejazi E, Amani R, Sharafodinzadeh N, Cheraghian B. Comparison of antioxidant status and vitamin D levels between multiple sclerosis patients and healthy matched subjects. Mult Scler Int 2014;2014:5.
   Google Scholar
• Gelfand JM, Cree BA, McElroy J, Oksenberg J, Green R, Mowry EM, et al. Vitamin D in African Americans with multiple sclerosis. Neurology 2011;76(21):1824–30.
   PubMed Web of Science ®Google Scholar
• Simpson Jr S, Taylor B, Blizzard L, Ponsonby AL, Pittas F, Tremlett H, et al. Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol 2010;68(2):193–203.
   PubMed Web of Science ®Google Scholar
• Knippenberg S, Damoiseaux J, Bol Y, Hupperts R, Taylor BV, Ponsonby AL, et al. Higher levels of reported sun exposure, and not vitamin D status, are associated with less depressive symptoms and fatigue in multiple sclerosis. Acta Neurol Scand 2014;129(2):123–31.
   PubMed Web of Science ®Google Scholar
• Loken-Amsrud KI, Holmoy T, Bakke SJ, Beiske AG, Bjerve KS, Bjornara BT, et al. Vitamin D and disease activity in multiple sclerosis before and during interferon-beta treatment. Neurology 2012;79(3):267–73.
   PubMed Web of Science ®Google Scholar
• Munger KL, Zhang SM, O’Reilly E, Hernán MA, Olek MJ, Willett WC, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology 2004;62(1):60–5.
   PubMed Web of Science ®Google Scholar
• Stein MS, Liu Y, Gray OM, Baker JE, Kolbe SC, Ditchfield MR, et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology 2011;77(17):1611–18.
   PubMed Web of Science ®Google Scholar
• Shaygannejad V, Janghorbani M, Ashtari F, Dehghan H. 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;2012:7.
   Google Scholar
• Kampman MT, Steffensen LH, Mellgren SI, Jorgensen L. 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 Web of Science ®Google Scholar
• Golan D, Halhal B, Glass-Marmor L, Staun-Ram E, Rozenberg O, Lavi I, et al. Vitamin D supplementation for patients with multiple sclerosis treated with interferon-beta: a randomized controlled trial assessing the effect on flu-like symptoms and immunomodulatory properties. BMC Neurol 2013;13:60.
   PubMed Web of Science ®Google Scholar
• Derakhshandi H, Etemadifar M, Feizi A, Abtahi SH, Minagar A, Abtahi MA, et al. Preventive effect of vitamin D3 supplementation on conversion of optic neuritis to clinically definite multiple sclerosis: a double blind, randomized, placebo-controlled pilot clinical trial. Acta Neurologica Belgica 2013;113(3):257–63.
   PubMed Web of Science ®Google Scholar
• Farsani ZS, Behmanesh M, Sahraian MA. Interleukin-10 but not transforming growth factor-β1 gene expression is up-regulated by vitamin D treatment in multiple. J Neurol Sci 2015;350(1–2):18–23.
   PubMed Web of Science ®Google Scholar
• Soilu-Hänninen M, Åivo J, Lindström BM, Elovaara I, Sumelahti ML, Färkkilä M, et al. A randomised, double blind, placebo controlled trial with vitamin D 3 as an add on treatment to interferon β-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2012;83(5):565–71.
   PubMed Web of Science ®Google Scholar
• Kim JS, Ryu SY, Yun I, Kim WJ, Lee KS, Park JW, 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 (Seoul, Korea). 2006;2(4):252–7.
   PubMedGoogle Scholar
• Cass WA, Peters LE, Fletcher AM, Yurek DM. Calcitriol promotes augmented dopamine release in the lesioned striatum of 6-hydroxydopamine treated rats. Neurochem Res 2014;39(8):1467–76.
   PubMed Web of Science ®Google Scholar
• Dean ED, Mexas LM, Capiro NL, McKeon JE, DeLong MR, Pennell KD, et al. 25-Hydroxyvitamin d depletion does not exacerbate MPTP-induced dopamine neuron damage in mice. PloS One 2012;7(7):e39227.
   PubMed Web of Science ®Google Scholar
• Zhu D, Liu GY, Lv Z, Wen SR, Bi S, Wang WZ. Inverse associations of outdoor activity and vitamin D intake with the risk of Parkinson’s disease. J Zhejiang Univ Sci B 2014;15(10):923–7.
   PubMed Web of Science ®Google Scholar
• Kwon E, Gallagher LG, Searles Nielsen S, Franklin GM, Littell CT, Longstreth WT, Jr., et al. Parkinson’s disease and history of outdoor occupation. Parkinsonism Relat Disord 2013;19(12):1164–6.
   PubMed Web of Science ®Google Scholar
• Miyake Y, Tanaka K, Fukushima W, Sasaki S, Kiyohara C, Tsuboi Y, et al. Lack of association of dairy food, calcium, and vitamin D intake with the risk of Parkinson’s disease: a case-control study in Japan. Parkinsonism Relat Disord 2011;17(2):112–16.
   PubMed Web of Science ®Google Scholar
• Wang J, Yang D, Yu Y, Shao G, Wang Q. Vitamin D and sunlight exposure in newly-diagnosed Parkinson’s disease. Nutrients 2016;8(3):142.
   PubMed Web of Science ®Google Scholar
• Wang LY, Evatt ML, Maldonado LG, Perry WR, Ritchie JC, Beecham GW, et al. Vitamin D from different sources Is inversely associated With Parkinson disease. Movement Disord 2015;30(4):560–6.
   PubMed Web of Science ®Google Scholar
• Yu J, Gattoni-Celli M, Zhu H, Bhat NR, Sambamurti K, Gattoni-Celli S, et al. Vitamin D3-enriched diet correlates with a decrease of amyloid plaques in the brain of AbetaPP transgenic mice. J Alzheimer’s Dis JAD 2011;25(2):295–307.
   PubMed Web of Science ®Google Scholar
• Taghizadeh M, Talaei SA, Djazayeri A, Salami M. Vitamin D supplementation restores suppressed synaptic plasticity in Alzheimer’s disease. Nutr Neurosci 2014;17(4):172–7.
   PubMed Web of Science ®Google Scholar
• Taghizadeh M, Djazayery A, Salami M, Eshraghian MR, Zavareh SA. Vitamin-D-free regimen intensifies the spatial learning deficit in Alzheimer’s disease. Int J Neurosci 2011;121(1):16–24.
   PubMed Web of Science ®Google Scholar
• Bennett L, Kersaitis C, Macaulay SL, Münch G, Niedermayer G, Nigro J, et al. Vitamin D2-enriched button mushroom (agaricus bisporus) improves memory in both wild type and APPswe/PS1dE9 transgenic mice. PloS One 2013;8(10):e76362.
   Web of Science ®Google Scholar
• Afzal S, Bojesen SE, Nordestgaard BG. Reduced 25-hydroxyvitamin D and risk of Alzheimer’s disease and vascular dementia. Alzheimers Dement 2014;10(3):296–302.
   PubMed Web of Science ®Google Scholar
• Annweiler C, Rolland Y, Schott AM, Blain H, Vellas B, Herrmann FR, et al. Higher vitamin D dietary intake is associated with lower risk of Alzheimer’s disease: A 7-year follow-up. J Gerontol Ser A: Biol Sci Med Sci 2012;67A(11):1205–11.
   Google Scholar
• Gangwar AK, Rawat A, Tiwari S, Tiwari SC, Narayan J, Tiwari S. Role of vitamin-D in the prevention and treatment of Alzheimer’s disease. Indian J Physiol Pharmacol 2015;59(1):94–9.
   PubMedGoogle Scholar
• Stein MS, Scherer SC, Ladd KS, Harrison LC. A randomized controlled trial of high-dose vitamin D2 followed by intranasal insulin in Alzheimer’s disease. J Alzheimer’s Dis JAD 2011;26(3):477–84.
   PubMed Web of Science ®Google Scholar
• Moghimi E, Solomon JA, Gianforcaro A, Hamadeh MJ. Dietary vitamin D3 restriction exacerbates disease pathophysiology in the spinal cord of the G93A mouse model of amyotrophic lateral sclerosis. PloS One 2015;10(5):23.
   Web of Science ®Google Scholar
• Solomon JA, Gianforcaro A, Hamadeh MJ. Vitamin D3 deficiency differentially affects functional and disease outcomes in the G93A mouse model of amyotrophic lateral sclerosis. PloS One 2011;6(12):e29354.
   PubMed Web of Science ®Google Scholar
• Gianforcaro A, Solomon JA, Hamadeh MJ. Vitamin D(3) at 50x AI attenuates the decline in paw grip endurance, but not disease outcomes, in the G93A mouse model of ALS, and is toxic in females. PloS One 2013;8(2):e30243.
   PubMed Web of Science ®Google Scholar
• Gianforcaro A, Hamadeh MJ. Dietary vitamin D3 supplementation at 10x the adequate intake improves functional capacity in the G93A transgenic mouse model of ALS, a pilot study. CNS Neurosci Ther 2012;18(7):547–57.
   PubMed Web of Science ®Google Scholar
• Karam C, Barrett MJ, Imperato T, MacGowan DJ, Scelsa S. Vitamin D deficiency and its supplementation in patients with amyotrophic lateral sclerosis. J Clin Neurosci Off J Neurosurg Soc Aust 2013;20(11):1550–3.
   PubMed Web of Science ®Google Scholar
• Antico A, Tampoia M, Tozzoli R, Bizzaro N. Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun Rev 2012;12(2):127–36.
   PubMed Web of Science ®Google Scholar
• Garcion E, Sindji L, Montero-Menei C, Andre C, Brachet P, Darcy F. Expression of inducible nitric oxide synthase during rat brain inflammation: regulation by 1,25-dihydroxyvitamin D3. Glia 1998;22(3):282–94.
   PubMed Web of Science ®Google Scholar
• Norval M, McLoone P, Lesiak A, Narbutt J. The effect of chronic ultraviolet radiation on the human immune system. Photochem Photobiol 2008;84(1):19–28.
   PubMed Web of Science ®Google Scholar
• Gray C, Gibbons R, Larouche R, Sandseter EB, Bienenstock A, Brussoni M, et al. What Is the relationship between outdoor time and physical activity, sedentary behaviour, and physical fitness in children? A systematic review. Int J Environ Res Public Health 2015;12(6):6455–74.
   PubMed Web of Science ®Google Scholar
• Bauman A, Merom D, Bull FC, Buchner DM, Fiatarone Singh MA. Updating the evidence for physical activity: summative reviews of the epidemiological evidence, prevalence, and interventions to promote ‘active aging’. Gerontologist 2016;56 Suppl 2:S268-S280.
   PubMedGoogle Scholar
• Mead MN. Benefits of sunlight: a bright spot for human health. Environ Health Perspect 2008;116(4):A160-A167.
   PubMed Web of Science ®Google Scholar
• Paillard T, Rolland Y, De souto barreto P. protective effects of physical exercise in Alzheimer’s disease and Parkinson’s disease: A narrative review. J Clin Neurol (Seoul, Korea) 2015;11(3):212–19.
   PubMed Web of Science ®Google Scholar
• Institute of medicine standing committee on the scientific evaluation of dietary reference I. The National Academies Collection: Reports funded by National Institutes of Health. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington (DC): National Academies Press (US); National Academy of Sciences.; 1997.
   Google Scholar
• Heaney RP. Guidelines for optimizing design and analysis of clinical studies of nutrient effects. Nutr Rev 2014;72(1):48–54.
   PubMed Web of Science ®Google Scholar
• Grant WB, Boucher BJ. Randomized controlled trials of vitamin D and cancer incidence: A modeling study. PloS One 2017;12(5):e0176448.
   PubMed Web of Science ®Google Scholar
• Holick MF. Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol 2009;19(2):73–8.
   PubMed Web of Science ®Google Scholar
• Grossmann RE, Tangpricha V. Evaluation of vehicle substances on vitamin D bioavailability: a systematic review. Mol Nutr Food Res 2010;54(8):1055–61.
   PubMed Web of Science ®Google Scholar