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Vitamin D Supplementation and Cognition in Adults: A Systematic Review of Randomized Controlled Trials

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Abstract

Background

The role of vitamin D supplementation in improving cognition and slowing the incidence of minor and major neurocognitive disorders is a matter of debate. To our knowledge, no systematic review of randomized controlled trials (RCTs) has examined this question in adults.

Objectives

The purpose of this systematic review is to synthesize the evidence regarding the effects of vitamin D supplementation on cognitive performance and neurocognitive disorders in adults.

Methods

A systematic search of scientific articles in English or French was conducted. The MEDLINE (PubMed), EMBASE (Ovid, EMBASE), PsychINFO, and Cochrane Central databases were searched for records without any limit on publication date in May 2021. Inclusion criteria were (1) human participants, (2) RCT, (3) participant age ≥ 18, (4) vitamin D supplementation as the intervention, and (5) cognition (i.e., cognitive performance or cognitive status such as cognitively healthy or minor and major neurocognitive disorder) as the primary outcome. Two independent reviewers both assessed all eligible studies’ full texts and the risk of bias arising from methodological issues using a standardized procedure.

Results

Of the 2137 abstracts identified, 61 (2.9%) met screening inclusion criteria. After full text examination, 41 records (67.2%) were excluded. As a result, 20 RCTs (32.8%) were included in the systematic review. The review yielded mixed findings and, thus, failed to find evidence supporting cognitive benefits from vitamin D supplementation or suggesting a causal association between vitamin D and cognitive function. Half of the RCTs reported mixed results, one quarter negative results, and the last quarter positive effects for vitamin D supplementation on cognitive performance. The variability in serum 25-dihydroxyvitamin D concentration thresholds, the cognitive tests employed, the supplementation doses, and the samples’ characteristics (i.e., ethnicity or number of participants) may explain these mixed findings.

Conclusion

This systematic review of RCTs does not support a role for vitamin D supplementation in enhancing cognition in adults.

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References

  1. Landel V, Annweiler C, Millet P, Morello M, Féron F, Vitamin D. Cognition and Alzheimer’s disease: the therapeutic benefit is in the D-tails. J Alzheimers Dis. 2016;53(2):419–44.

    Article  CAS  Google Scholar 

  2. Suh SW, Kim HS, Han JH, Bae JB, Oh DJ, Han JW, Kim KW. Efficacy of vitamins on cognitive function of non-demented people: a systematic review and meta-analysis. Nutrients. 2020;12(4):1168.

    Article  CAS  Google Scholar 

  3. Littlejohns TJ, Henley WE, Lang IA, Annweiler C, Beauchet O, Chaves PH, Fried L, Kestenbaum BR, Kuller LH, Langa KM, Lopez OL, Kos K, Soni M, Llewellyn DJ. Vitamin D and the risk of dementia and Alzheimer disease. Neurology. 2014;83(10):920–8.

    Article  CAS  Google Scholar 

  4. Annweiler C, Montero-Odasso M, Llewellyn DJ, Richard-Devantoy S, Duque G, Beauchet O. Meta-analysis of memory and executive dysfunctions in relation to vitamin D. J Alzheimers Dis. 2013;37(1):147–71.

    Article  CAS  Google Scholar 

  5. Balion C, Griffith LE, Strifler L, Henderson M, Patterson C, Heckman G, Llewellyn DJ, Raina P. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology. 2012;79(13):1397–405.

    Article  CAS  Google Scholar 

  6. Farghali M, Ruga S, Morsanuto V, Uberti F. Can brain health be supported by vitamin D-based supplements? A critical review. Brain Sci. 2020;10(9):660.

    Article  CAS  Google Scholar 

  7. Caristia S, Filigheddu N, Barone-Adesi F, Sarro A, Testa T, Magnani C, Aimaretti G, Faggiano F, Marzullo P. Vitamin D as a biomarker of ill health among the over-50s: a systematic review of cohort studies. Nutrients. 2019;11(10):2384.

    Article  CAS  Google Scholar 

  8. Annweiler C, Beauchet O. Vitamin D-mentia: randomized clinical trials should be the next step. Neuroepidemiology. 2011;37(3–4):249–58.

    Article  Google Scholar 

  9. Maddock J, Zhou A, Cavadino A, Kuźma E, Bao Y, Smart MC, Saum KU, Schöttker B, Engmann J, Kjærgaard M, Karhunen V, Zhan Y, Lehtimäki T, Rovio SP, Byberg L, Lahti J, Marques-Vidal P, Sen A, Perna L, Schirmer H, Singh-Manoux A, Auvinen J, Hutri-Kähönen N, Kähönen M, Kilander L, Räikkönen K, Melhus H, Ingelsson E, Guessous I, Petrovic KE, Schmidt H, Schmidt R, Vollenweider P, Lind L, Eriksson JG, Michaëlsson K, Raitakari OT, Hägg S, Pedersen NL, Herzig KH, Järvelin MR, Veijola J, Kivimaki M, Jorde R, Brenner H, Kumari M, Power C, Llewellyn DJ, Hyppönen E. Vitamin D and cognitive function: a Mendelian randomisation study. Sci Rep. 2017;7(1):13230.

    Article  Google Scholar 

  10. Mayer F, Remoli G, Bacigalupo I, Palazzesi I, Piscopo P, Bellomo G, Canevelli M, Corbo M, Vanacore N, Lacorte E. A systematic review of studies reporting a decreasing trend in the incidence and prevalence of dementia. Minerva Med. 2021. https://doi.org/10.23736/S0026-4806.21.07454-1.

    Article  PubMed  Google Scholar 

  11. Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, Brayne C, Burns A, Cohen-Mansfield J, Cooper C, Costafreda SG, Dias A, Fox N, Gitlin LN, Howard R, Kales HC, Kivimäki M, Larson EB, Ogunniyi A, Orgeta V, Ritchie K, Rockwood K, Sampson EL, Samus Q, Schneider LS, Selbæk G, Teri L, Mukadam N. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396(10248):413–46.

    Article  Google Scholar 

  12. Boutron I, Altman DG, Moher D, Schulz KF, Ravaud P, CONSORT NPT Group. CONSORT statement for randomized trials of nonpharmacologic treatments: a 2017 update and a CONSORT extension for nonpharmacologic trial abstracts. Ann Intern Med. 2017;167(1):40–7.

    Article  Google Scholar 

  13. Han JH, Ginde AA, Brown SM, Baughman A, Collar EM, Ely EW, Gong MN, Hope AA, Hou PC, Hough CL, Iwashyna TJ, Jackson JC, Khan A, Orun OM, Patel MB, Raman R, Rice TW, Ringwood N, Semler MW, Shapiro NI, Talmor DS, Self WH; Vitamin D to Improve Outcomes by Leveraging Early Treatment Network Investigators. Effect of early high-dose vitamin D3 repletion on cognitive outcomes in critically ill adults. Chest. 2021;160(3):909–18.

    Article  CAS  Google Scholar 

  14. Yang T, Wang H, Xiong Y, Chen C, Duan K, Jia J, Ma F. 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.

    Article  CAS  Google Scholar 

  15. Ghaderi A, Rasouli-Azad M, Farhadi MH, Mirhosseini N, Motmaen M, Pishyareh E, Omidi A, Asemi Z. Exploring the effects of vitamin D supplementation on cognitive functions and mental health status in subjects under methadone maintenance treatment. J Addict Med. 2020;14(1):18–25.

    Article  CAS  Google Scholar 

  16. 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.

    Article  CAS  Google Scholar 

  17. Castle M, Fiedler N, Pop LC, Schneider SJ, Schlussel Y, Sukumar D, Hao L, Shapses SA. 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.

    Article  CAS  Google Scholar 

  18. Beauchet O, Launay CP, Galery K, Vilcocq C, Dontot-Payen F, Rousseau B, Benoit V, Allali G. 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.

    Article  Google Scholar 

  19. 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;30(2019):5696391.

    Google Scholar 

  20. Jia J, Hu J, Huo X, Miao R, Zhang Y, Ma F. Effects of vitamin D supplementation on cognitive function and blood Abeta-related biomarkers in older adults with Alzheimer’s disease: a randomised, double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry. 2019;90(12):1347–52.

    PubMed  Google Scholar 

  21. Schietzel S, Fischer K, Brugger P, Orav EJ, Renerts K, Gagesch M, Freystaetter G, Stähelin HB, Egli A, Bischoff-Ferrari HA. 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.

    Article  Google Scholar 

  22. Jorde R, Kubiak J, Svartberg J, Fuskevåg OM, Figenschau Y, Martinaityte I, Grimnes G. Vitamin D supplementation has no effect on cognitive performance after four months in mid-aged and older subjects. J Neurol Sci. 2019;15(396):165–71.

    Article  Google Scholar 

  23. Owusu JE, Islam S, Katumuluwa SS, Stolberg AR, Usera GL, Anwarullah AA, Shieh A, Dhaliwal R, Ragolia L, Mikhail MB, Aloia JF. 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.

    Article  Google Scholar 

  24. Hu J, Jia J, Zhang Y, Miao R, Huo X, Ma F. Effects of vitamin D3 supplementation on cognition and blood lipids: a 12-month randomised, double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry. 2018;89(12):1341–7.

    Article  Google Scholar 

  25. Krivoy A, Onn R, Vilner Y, Hochman E, Weizman S, Paz A, Hess S, Sagy R, Kimhi-Nesher S, Kalter E, Friedman T, Friedman Z, Bormant G, Trommer S, Valevski A, Weizman A. Vitamin D supplementation in chronic schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled clinical trial. EBioMedicine. 2017;26:138–45.

    Article  Google Scholar 

  26. Pettersen JA. Does high dose vitamin D supplementation enhance cognition?: A randomized trial in healthy adults. Exp Gerontol. 2017;90:90–7.

    Article  CAS  Google Scholar 

  27. Suzuki M, Yoshioka M, Hashimoto M, Murakami M, Noya M, Takahashi D, Urashima M. Randomized, double-blind, placebo-controlled trial of vitamin D supplementation in Parkinson disease. Am J Clin Nutr. 2013;97(5):1004–13.

    Article  CAS  Google Scholar 

  28. Rossom RC, Espeland MA, Manson JE, Dysken MW, Johnson KC, Lane DS, LeBlanc ES, Lederle FA, Masaki KH, Margolis KL. Calcium and vitamin D supplementation and cognitive impairment in the women’s health initiative. J Am Geriatr Soc. 2012;60(12):2197–205.

    Article  Google Scholar 

  29. Dean AJ, Bellgrove MA, Hall T, Phan WM, Eyles DW, Kvaskoff D, McGrath JJ. Effects of vitamin D supplementation on cognitive and emotional functioning in young adults–a randomised controlled trial. PLoS ONE. 2011;6(11):e25966.

    Article  CAS  Google Scholar 

  30. 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.

    Article  CAS  Google Scholar 

  31. Dhesi JK, Jackson SH, Bearne LM, Moniz C, Hurley MV, Swift CG, Allain TJ. Vitamin D supplementation improves neuromuscular function in older people who fall. Age Ageing. 2004;33(6):589–95.

    Article  Google Scholar 

  32. Corless D, Dawson E, Fraser F, Ellis M, Evans SJ, Perry JD, Reisner C, Silver CP, Beer M, Boucher BJ. Do vitamin D supplements improve the physical capabilities of elderly hospital patients? Age Ageing. 1985;14(2):76–84.

    Article  CAS  Google Scholar 

  33. Spieth PM, Kubasch AS, Penzlin AI, Illigens BM, Barlinn K, Siepmann T. Randomized controlled trials—a matter of design. Neuropsychiatr Dis Treat. 2016;10(12):1341–9.

    Google Scholar 

  34. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 dietary reference intakes for calcium and vitamin D: what dietetics practitioners need to know. J Am Diet Assoc. 2011;111(4):524–7.

    Article  CAS  Google Scholar 

  35. Mazahery H, von Hurst PR. Factors affecting 25Hydroxyvitamin D concentration in response to vitamin D supplementation. Nutrients. 2015;7(7):5111–42.

    Article  CAS  Google Scholar 

  36. Powe CE, Evans MK, Wenger J, Zonderman AB, Berg AH, Nalls M, Tamez H, Zhang D, Bhan I, Karumanchi SA, Powe NR, Thadhani R. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med. 2013;369(21):1991–2000.

    Article  CAS  Google Scholar 

  37. Brown LL, Cohen B, Tabor D, Zappalà G, Maruvada P, Coates PM. The vitamin D paradox in Black Americans: a systems-based approach to investigating clinical practice, research, and public health—expert panel meeting report. BMC Proc. 2018;12(Suppl 6):6.

    Article  Google Scholar 

  38. Aloia JF, Vaswani A, Feuerman M, Mikhail M, Ma R. Differences in skeletal and muscle mass with aging in black and white women. Am J Physiol Endocrinol Metab. 2000;278(6):E1153–7.

    Article  CAS  Google Scholar 

  39. Cherniack EP, Florez H, Roos BA, Troen BR, Levis S. Hypovitaminosis D in the elderly: from bone to brain. J Nutr Health Aging. 2008;12(6):366–73.

    Article  CAS  Google Scholar 

  40. Williams S, Malatesta K, Norris K. Vitamin D and chronic kidney disease. Ethn Dis. 2009;19(4 Suppl 5):S5-8–11.

    PubMed  Google Scholar 

  41. Seldeen KL, Troen BR. Pinpointing a role for vitamin D in frailty: a time for animal models? Adv Geriatr Med Res. 2021;3(2):e210007.

    PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicine, University of Montreal, Montreal, QC, Canada

    Olivier Beauchet

  2. Research Center of the Geriatric University Institute of Montreal, Montreal, QC, Canada

    Olivier Beauchet

  3. Division of Geriatric Medicine, Department of Medicine, Sir Mortimer B. Davis Jewish General Hospital and Lady Davis Institute for Medical Research, McGill University, Montreal, QC, Canada

    Olivier Beauchet

  4. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

    Olivier Beauchet

  5. Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada

    Liam A. Cooper-Brown

  6. Leenaards Memory Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

    Gilles Allali

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  1. Olivier Beauchet
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Correspondence to Olivier Beauchet.

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Funding

The study was not financially supported.

Conflicts of interest

The authors declare that they have no potential conflicts of interest.

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Author contributions

Conceived of and designed the experiments: OB and GA. Analyzed and interpreted the data: OB, LACB, and GA. Contributed reagents, materials, analysis tools, or data: OB. Writing of the manuscript: OB. Revision of manuscript: GA and LACB. All authors approve the final version of the manuscript for submission and publication and agree to be accountable for the work presented in the article.

Data statement

Data will be made available on request sent by e-mail to Dr. Beauchet (olivier.beauchet@umontreal.ca).

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Beauchet, O., Cooper-Brown, L.A. & Allali, G. Vitamin D Supplementation and Cognition in Adults: A Systematic Review of Randomized Controlled Trials. CNS Drugs 35, 1249–1264 (2021). https://doi.org/10.1007/s40263-021-00876-z

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