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CNS & Neurological Disorders - Drug Targets

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ISSN (Online): 1996-3181

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Systematic Review Article

The Potential Role of Vitamin D Supplementation in Cognitive Impairment Prevention

Author(s): Iris Zeqaj, Roberto Piffero*, Elisa Calzaducca, Mario Pirisi and Mattia Bellan

Volume 23, Issue 5, 2024

Published on: 04 May, 2023

Page: [628 - 637] Pages: 10

DOI: 10.2174/1871527322666230328130417

Price: $65

Abstract

Background: Vitamin D is implicated in many processes in the central nervous system (CNS), such as neurogenesis, neurotransmitter synthesis, synaptogenesis and protection against oxidative stress, thereby exerting a neuroprotective effect.

Objective: In the present review, we aimed to evaluate the potential benefit(s) of vitamin D supplementation for CNS aging in different clinical contexts.

Methods: We performed a literature search, looking for clinical trials and randomized clinical trials evaluating the effect of vitamin D supplementation on different endpoints related to cognitive outcomes.

Results: Firstly, we identified 16 papers dealing with the impact of vitamin D supplementation on cognitive function in healthy subjects; the current literature suggests a real role for vitamin D supplementation in the prevention of cognitive decay in this clinical setting. Conversely, two papers suggest that vitamin D supplementation may be beneficial in patients with mild cognitive impairment (MCI). Finally, current data on vitamin D in Alzheimer’s disease are contradictory.

Conclusion: Vitamin D supplementation may improve the cognitive outcomes of patients with MCI, whereas there is no evidence that it may prevent dementia or modulate the course of Alzheimer’s disease.

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[1]
Kumar R. Vitamin D metabolism and mechanisms of calcium transport. J Am Soc Nephrol 1990; 1: 30 LP-42.
[2]
Tripkovic L, Lambert H, Hart K, et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr 2012; 95(6): 1357-64.
[http://dx.doi.org/10.3945/ajcn.111.031070] [PMID: 22552031]
[3]
Heaney RP, Recker RR, Grote J, Horst RL, Armas LAG. Vitamin D(3) is more potent than vitamin D(2) in humans. J Clin Endocrinol Metab 2011; 96(3): E447-52.
[http://dx.doi.org/10.1210/jc.2010-2230] [PMID: 21177785]
[4]
Lips P. Relative value of 25(OH)D and 1,25(OH)2D measurements. J Bone Miner Res 2007; 22(11): 1668-71.
[http://dx.doi.org/10.1359/jbmr.070716] [PMID: 17645404]
[5]
Deluca HF. History of the discovery of vitamin D and its active metabolites. Bonekey Rep 2014; 3: 479.
[http://dx.doi.org/10.1038/bonekey.2013.213]
[6]
Fleet JC. The role of vitamin D in the endocrinology controlling calcium homeostasis. Mol Cell Endocrinol 2017; 453: 36-45.
[http://dx.doi.org/10.1016/j.mce.2017.04.008] [PMID: 28400273]
[7]
Hii CS, Ferrante A. The non-genomic actions of vitamin D. Nutrients 2016; 8: 135.
[http://dx.doi.org/10.3390/nu8030135]
[8]
Bikle DD. Vitamin D and bone. Curr Osteoporos Rep 2012; 10(2): 151-9.
[http://dx.doi.org/10.1007/s11914-012-0098-z] [PMID: 22544628]
[9]
Zehnder D, Bland R, Williams MC, et al. Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab 2001; 86(2): 888-94.
[PMID: 11158062]
[10]
Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006; 311(5768): 1770-3.
[http://dx.doi.org/10.1126/science.1123933] [PMID: 16497887]
[11]
Schauber J, Dorschner RA, Coda AB, et al. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D–dependent mechanism. J Clin Invest 2007; 117(3): 803-11.
[http://dx.doi.org/10.1172/JCI30142] [PMID: 17290304]
[12]
Wang TT, Nestel FP, Bourdeau V, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 2004; 173(5): 2909-12.
[http://dx.doi.org/10.4049/jimmunol.173.5.2909] [PMID: 15322146]
[13]
Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol 2007; 179(3): 1634-47.
[http://dx.doi.org/10.4049/jimmunol.179.3.1634] [PMID: 17641030]
[14]
Lemire JM, Archer DC, Beck L, Spiegelberg HL. Immunosuppressive actions of 1,25-dihydroxyvitamin D3: Preferential inhibition of Th1 functions. J Nutr 1995; 125(6): 1704S-8S.
[PMID: 7782931]
[15]
Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HFJ, O’Garra A. 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 2001; 167(9): 4974-80.
[http://dx.doi.org/10.4049/jimmunol.167.9.4974] [PMID: 11673504]
[16]
Hawker NP, Pennypacker SD, Chang SM, Bikle DD. Regulation of human epidermal keratinocyte differentiation by the vitamin D receptor and its coactivators DRIP205, SRC2, and SRC3. J Invest Dermatol 2007; 127(4): 874-80.
[http://dx.doi.org/10.1038/sj.jid.5700624] [PMID: 17082781]
[17]
Bikle DD, Pillai S. Vitamin D, calcium, and epidermal differentiation. Endocr Rev 1993; 14(1): 3-19.
[PMID: 8491153]
[18]
Peehl DM, Skowronski RJ, Leung GK, Wong ST, Stamey TA, Feldman D. Antiproliferative effects of 1,25-dihydroxyvitamin D3 on primary cultures of human prostatic cells. Cancer Res 1994; 54(3): 805-10.
[PMID: 7508338]
[19]
Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab 2009; 94(1): 26-34.
[http://dx.doi.org/10.1210/jc.2008-1454] [PMID: 18854395]
[20]
Demay MB, Kiernan MS, DeLuca HF, Kronenberg HM. Sequences in the human parathyroid hormone gene that bind the 1,25-dihydroxyvitamin D3 receptor and mediate transcriptional repression in response to 1,25-dihydroxyvitamin D3. Proc Natl Acad Sci 1992; 89: 8097-80101. Available from: https://www.pnas.org/doi/epdf/10.1073/pnas.89.17.8097
[21]
Lee S, Clark SA, Gill RK, Christakos S. 1,25-Dihydroxyvitamin D3 and pancreatic beta-cell function: vitamin D receptors, gene expression, and insulin secretion. Endocrinology 1994; 134(4): 1602-10.
[http://dx.doi.org/10.1210/endo.134.4.8137721] [PMID: 8137721]
[22]
Bellan M, Andreoli L, Mele C, et al. Pathophysiological role and therapeutic implications of vitamin D in autoimmunity: focus on chronic autoimmune diseases. Nutrients 2020; 12: 789.
[http://dx.doi.org/10.3390/nu12030789]
[23]
Bellan M, Sainaghi PP, Pirisi M. Role of vitamin D in rheumatoid arthritis. Adv Exp Med Biol 2017; 996: 155-68.
[http://dx.doi.org/10.1007/978-3-319-56017-5_13] [PMID: 29124698]
[24]
Bellan M, Pirisi M, Sainaghi PP. Osteoporose na artrite reumatoide: Papel do sistema vitamina D/hormônio paratireóideo. Rev Bras Reumatol 2015; 55: 256-63.
[http://dx.doi.org/10.1016/j.rbr.2014.10.007]
[25]
Sainaghi PP, Bellan M, Antonini G, Bellomo G, Pirisi M. Unsuppressed parathyroid hormone in patients with autoimmune/inflammatory rheumatic diseases: Implications for vitamin D supplementation. Rheumatology 2011; 50(12): 2290-6.
[http://dx.doi.org/10.1093/rheumatology/ker314] [PMID: 22019806]
[26]
Sainaghi PP, Bellan M, Carda S, et al. Hypovitaminosis D and response to cholecalciferol supplementation in patients with autoimmune and non-autoimmune rheumatic diseases. Rheumatol Int 2012; 32(11): 3365-72.
[http://dx.doi.org/10.1007/s00296-011-2170-x] [PMID: 22045518]
[27]
Bellan M, Andreoli L, Nerviani A, et al. Is cholecalciferol a potential disease-modifying anti-rheumatic drug for the management of rheumatoid arthritis? Clin Exp Rheumatol 2020; 38(2): 343-9.
[http://dx.doi.org/10.55563/clinexprheumatol/tdf172] [PMID: 31573472]
[28]
Berridge MJ. Vitamin D deficiency accelerates ageing and age-related diseases: A novel hypothesis. J Physiol 2017; 595(22): 6825-36.
[http://dx.doi.org/10.1113/JP274887] [PMID: 28949008]
[29]
Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ. Distribution of the Vitamin D receptor and 1α-hydroxylase in human brain. J Chem Neuroanat 2005; 29(1): 21-30.
[http://dx.doi.org/10.1016/j.jchemneu.2004.08.006] [PMID: 15589699]
[30]
Brown J, Bianco JI, McGrath JJ, Eyles DW. 1,25-dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neurosci Lett 2003; 343(2): 139-43.
[http://dx.doi.org/10.1016/S0304-3940(03)00303-3] [PMID: 12759183]
[31]
Brouwer-Brolsma EM, de Groot LCPGM. Vitamin D and cognition in older adults. Curr Opin Clin Nutr Metab Care 2015; 18(1): 11-6.
[http://dx.doi.org/10.1097/MCO.0000000000000114] [PMID: 25225898]
[32]
Sultan S, Taimuri U, Basnan SA, et al. Low vitamin D and its association with cognitive impairment and dementia. J Aging Res 2020; 2020: 6097820.
[http://dx.doi.org/10.1155/2020/6097820]
[33]
Latimer CS, Brewer LD, Searcy JL, et al. Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats. Proc Natl Acad Sci 2014; 111: E4359-66.
[http://dx.doi.org/10.1073/pnas.1404477111] [PMID: 25267625]
[34]
Mokhtari-Zaer A, Hosseini M, Salmani H, Arab Z, Zareian P. Vitamin D3 attenuates lipopolysaccharide-induced cognitive impairment in rats by inhibiting inflammation and oxidative stress. Life Sci 2020; 253: 117703.
[http://dx.doi.org/10.1016/j.lfs.2020.117703] [PMID: 32334010]
[35]
de Oliveira LRC, Mimura LAN, Fraga-Silva TF de C, et al. Calcitriol prevents neuroinflammation and reduces blood-brain barrier disruption and local macrophage/microglia activation. Front Pharmacol 2020; 11: 161.
[http://dx.doi.org/10.3389/fphar.2020.00161] [PMID: 32226379]
[36]
Calvello R, Cianciulli A, Nicolardi G, et al. Vitamin D treatment attenuates neuroinflammation and dopaminergic neurodegeneration in an animal model of Parkinson’s disease, shifting M1 to M2 microglia responses. J Neuroimmune Pharmacol 2017; 12(2): 327-39.
[http://dx.doi.org/10.1007/s11481-016-9720-7] [PMID: 27987058]
[37]
Bao Z, Wang X, Li Y, Feng F. Vitamin D alleviates cognitive dysfunction by activating the VDR/ERK1/2 signaling pathway in an Alzheimer’s disease mouse model. Neuroimmunomodulation 2020; 27(4): 178-85.
[http://dx.doi.org/10.1159/000510400] [PMID: 33601398]
[38]
Landel V, Millet P, Baranger K, Loriod B, Féron F. Vitamin D interacts with Esr1 and Igf1 to regulate molecular pathways relevant to Alzheimer’s disease. Mol Neurodegener 2016; 11: 22.
[http://dx.doi.org/10.1186/s13024-016-0087-2] [PMID: 26932723]
[39]
Mizwicki MT, Menegaz D, Zhang J, et al. Genomic and nongenomic signaling induced by 1α25(OH)2-vitamin D3 promotes the recovery of amyloid-β phagocytosis by Alzheimer’s disease macrophages. J Alzheimers Dis 2012; 29(1): 51-62.
[http://dx.doi.org/10.3233/JAD-2012-110560] [PMID: 22207005]
[40]
Rossom RC, Espeland MA, Manson JE, et al. Calcium and vitamin D supplementation and cognitive impairment in the women’s health initiative. J Am Geriatr Soc 2012; 60(12): 2197-205.
[http://dx.doi.org/10.1111/jgs.12032] [PMID: 23176129]
[41]
Bischoff-Ferrari HA, Vellas B, Rizzoli R, et al. Effect of vitamin D supplementation, omega-3 fatty acid supplementation, or a strength-training exercise program on clinical outcomes in older adults: the DO-HEALTH randomized clinical trial. JAMA 2020; 324(18): 1855-68.
[http://dx.doi.org/10.1001/jama.2020.16909] [PMID: 33170239]
[42]
Moran C, Scotto di Palumbo A, Bramham J, et al. Effects of a six-month multi-ingredient nutrition supplement intervention of omega-3 polyunsaturated fatty acids, vitamin D, resveratrol, and Whey protein on cognitive function in older adults: a randomised, double-blind, controlled trial. J Prev Alzheimers Dis 2018; 5: 175-83.
[43]
Schietzel S, Fischer K, Brugger P, et al. Effect of 2000 IU compared with 800 IU vitamin D on cognitive performance among adults age 60 years and older: A randomized controlled trial. Am J Clin Nutr 2019; 110(1): 246-53.
[http://dx.doi.org/10.1093/ajcn/nqz081] [PMID: 31152541]
[44]
Zajac IT, Barnes M, Cavuoto P, Wittert G, Noakes M. The effects of vitamin D-enriched mushrooms and vitamin D3 on cognitive performance and mood in healthy elderly adults: A randomised, double-blinded, placebo-controlled trial. Nutrients 2020; 12(12): 3847.
[45]
Beauchet O, Launay CP, Galery K, et al. Effects of vitamin D and calcium fortified yogurts on gait, cognitive performances, and serum 25-hydroxyvitamin D concentrations in older community-dwelling females: Results from the gait, memory, dietary and vitamin D (GAME-D2) randomized controlled trial. Nutrients 2019; 11(12): 2880.
[http://dx.doi.org/10.3390/nu11122880] [PMID: 31779179]
[46]
Castle M, Fiedler N, Pop LC, et al. Three doses of vitamin D and cognitive outcomes in older women: a double-blind randomized controlled trial. J Gerontol A Biol Sci Med Sci 2020; 75(5): 835-42.
[http://dx.doi.org/10.1093/gerona/glz041] [PMID: 30951148]
[47]
Owusu JE, Islam S, Katumuluwa SS, et al. Cognition and vitamin D in older african-american women- physical performance and osteoporosis prevention with vitamin D in older african americans trial and dementia. J Am Geriatr Soc 2019; 67(1): 81-6.
[http://dx.doi.org/10.1111/jgs.15607] [PMID: 30359476]
[48]
Jorde R, Kubiak J, Svartberg J, et al. Vitamin D supplementation has no effect on cognitive performance after four months in mid-aged and older subjects. J Neurol Sci 2019; 396: 165-71.
[http://dx.doi.org/10.1016/j.jns.2018.11.020] [PMID: 30472553]
[49]
Przybelski R, Agrawal S, Krueger D, Engelke JA, Walbrun F, Binkley N. Rapid correction of low vitamin D status in nursing home residents. Osteoporos Int 2008; 19(11): 1621-8.
[http://dx.doi.org/10.1007/s00198-008-0619-x] [PMID: 18421544]
[50]
Pettersen JA. Does high dose vitamin D supplementation enhance cognition: A randomized trial in healthy adults. Exp Gerontol 2017; 90: 90-7.
[http://dx.doi.org/10.1016/j.exger.2017.01.019] [PMID: 28167237]
[51]
Byrn MA, Adams W, Penckofer S, Emanuele MA. Vitamin D supplementation and cognition in people with type 2 diabetes: A randomized control trial. J Diabetes Res 2019; 2019: 5696391.
[http://dx.doi.org/10.1155/2019/5696391] [PMID: 31781666]
[52]
Kang JH, Vyas CM, Okereke OI, et al. Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial. Sci Rep 2021; 11: 23253.
[http://dx.doi.org/10.1038/s41598-021-02485-8]
[53]
Dean AJ, Bellgrove MA, Hall T, et al. Effects of vitamin D supplementation on cognitive and emotional functioning in young adults-a randomised controlled trial. PLoS One 2011; 6: e25966.
[http://dx.doi.org/10.1371/journal.pone.0025966]
[54]
Abe S, Ezaki O, Suzuki M. Medium-chain triglycerides in combination with leucine and vitamin D benefit cognition in frail elderly adults: a randomized controlled trial. J Nutr Sci Vitaminol 2017; 63(2): 133-40.
[http://dx.doi.org/10.3177/jnsv.63.133] [PMID: 28552878]
[55]
Pham H, Waterhouse M, Rahman S, et al. Vitamin D supplementation and cognition-Results from analyses of the D-Health trial. J Am Geriatr Soc 2023.
[http://dx.doi.org/10.1111/jgs.18247]
[56]
Nasreddine ZS, Phillips NA, Bédirian V, et al. The montreal cognitive assessment, MoCA: A brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005; 53(4): 695-9.
[http://dx.doi.org/10.1111/j.1532-5415.2005.53221.x] [PMID: 15817019]
[57]
Yang T, Wang H, Xiong Y, et al. Vitamin D supplementation improves cognitive function through reducing oxidative stress regulated by telomere length in older adults with mild cognitive impairment: A 12-month randomized controlled trial. J Alzheimers Dis 2020; 78(4): 1509-18.
[http://dx.doi.org/10.3233/JAD-200926] [PMID: 33164936]
[58]
Hu J, Jia J, Zhang Y, Miao R, Huo X, Ma F. Effects of vitamin D3 supplementation on cognition and blood lipids: 12-month randomised, double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry 2018; 89(12): 1341-7.
[http://dx.doi.org/10.1136/jnnp-2018-318594] [PMID: 30279212]
[59]
Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004; 256(3): 183-94.
[http://dx.doi.org/10.1111/j.1365-2796.2004.01388.x] [PMID: 15324362]
[60]
Arvanitakis Z, Capuano AW, Bennett DA, Barnes LL. Body mass index and decline in cognitive function in older black and white persons. J Gerontol A Biol Sci Med Sci 2018; 73(2): 198-203.
[http://dx.doi.org/10.1093/gerona/glx152] [PMID: 28961897]
[61]
Tadic M, Cuspidi C, Hering D. Hypertension and cognitive dysfunction in elderly: blood pressure management for this global burden. BMC Cardiovasc Disord 2016; 16: 208.
[http://dx.doi.org/10.1186/s12872-016-0386-0]
[62]
Koch M, Fitzpatrick AL, Rapp SR, et al. Alcohol consumption and risk of dementia and cognitive decline among older adults with or without mild cognitive impairment. JAMA Netw Open 2019; 2: e1910319.
[http://dx.doi.org/10.1001/jamanetworkopen.2019.10319]
[63]
Montero-Odasso M, Almeida QJ, Burhan AM, et al. SYNERGIC TRIAL (Synchronizing Exercises, Remedies in Gait and Cognition) a multi-Centre randomized controlled double blind trial to improve gait and cognition in mild cognitive impairment. BMC Geriatr 2018; 18: 93.
[http://dx.doi.org/10.1186/s12877-018-0782-7]
[64]
Jia J, Hu J, Huo X, Miao R, Zhang Y, Ma F. Effects of vitamin D supplementation on cognitive function and blood Aβ-related biomarkers in older adults with Alzheimer’s disease: A randomised, double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry 2019; 90(12): jnnp-2018-320199.
[http://dx.doi.org/10.1136/jnnp-2018-320199] [PMID: 31296588]
[65]
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 Alzheimers Dis 2011; 26(3): 477-84.
[http://dx.doi.org/10.3233/JAD-2011-110149] [PMID: 21694461]
[66]
Annweiler C, Herrmann FR, Fantino B, Brugg B, Beauchet O. Effectiveness of the combination of memantine plus vitamin D on cognition in patients with Alzheimer disease: a pre-post pilot study. Cogn Behav Neurol 2012; 25(3): 121-7.
[http://dx.doi.org/10.1097/WNN.0b013e31826df647] [PMID: 22960436]
[67]
Llewellyn DJ, Lang IA, Langa KM, et al. Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med 2010; 170(13): 1135-41.
[http://dx.doi.org/10.1001/archinternmed.2010.173] [PMID: 20625021]
[68]
Etgen T, Sander D, Bickel H, Sander K, Förstl H. Vitamin D deficiency, cognitive impairment and dementia: A systematic review and meta-analysis. Dement Geriatr Cogn Disord 2012; 33(5): 297-305.
[http://dx.doi.org/10.1159/000339702] [PMID: 22759681]
[69]
Goodwill AM, Szoeke C. A systematic review and meta-analysis of the effect of low vitamin D on cognition. J Am Geriatr Soc 2017; 65(10): 2161-8.
[http://dx.doi.org/10.1111/jgs.15012] [PMID: 28758188]
[70]
Kalra A, Teixeira AL, Diniz BS. Association of vitamin D levels with incident all-cause dementia in longitudinal observational studies: A systematic review and meta-analysis. J Prev Alzheimers Dis 2020; 7: 14-20.
[71]
Sommer I, Griebler U, Kien C, et al. Vitamin D deficiency as a risk factor for dementia: a systematic review and meta-analysis. BMC Geriatr 2017; 17: 16.
[72]
Shen L, Ji H-F. Vitamin D deficiency is associated with increased risk of Alzheimer’s disease and dementia: evidence from meta-analysis. Nutr J 2015; 14: 76.
[73]
Jayedi A, Rashidy-Pour A, Shab-Bidar S. Vitamin D status and risk of dementia and Alzheimer’s disease: A meta-analysis of dose-response. Nutr Neurosci 2019; 22(11): 750-9.
[http://dx.doi.org/10.1080/1028415X.2018.1436639] [PMID: 29447107]
[74]
Karakis I, Pase MP, Beiser A, et al. Association of serum vitamin D with the risk of incident dementia and subclinical indices of brain aging: The Framingham heart study. J Alzheimers Dis 2016; 51(2): 451-61.
[http://dx.doi.org/10.3233/JAD-150991] [PMID: 26890771]
[75]
Al-Amin M, Bradford D, Sullivan RKP, et al. Vitamin D deficiency is associated with reduced hippocampal volume and disrupted structural connectivity in patients with mild cognitive impairment. Hum Brain Mapp 2019; 40(2): 394-406.
[http://dx.doi.org/10.1002/hbm.24380] [PMID: 30251770]
[76]
Rizzoli R, Stoermann C, Ammann P, Bonjour JP. Hypercalcemia and hyperosteolysis in vitamin D intoxication: Effects of clodronate therapy. Bone 1994; 15(2): 193-8.
[http://dx.doi.org/10.1016/8756-3282(94)90707-2] [PMID: 8086237]
[77]
Pilz S, März W, Cashman KD, et al. Rationale and Plan for Vitamin D Food Fortification: A review and guidance paper. Front Endocrinol 2018; 9: 373.
[78]
Rizzoli R. Vitamin D supplementation: Upper limit for safety revisited? Aging Clin Exp Res 2021; 33(1): 19-24.
[http://dx.doi.org/10.1007/s40520-020-01678-x] [PMID: 32857334]
[79]
Xu Z, Zhang D, Sit RWS, et al. Incidence of and risk factors for mild cognitive impairment in chinese older adults with multimorbidity in Hong Kong. Sci Rep 2020; 10: 4137.
[http://dx.doi.org/10.1038/s41598-020-60901-x]

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