Parkinson Disease

Parkinson disease is another progressive neurodegenerative disease and involves dopaminergic neuronal loss.1 Motor symptoms include bradykinesia, rigidity, tremor, gait disorders, and postural instability.15 Although human studies examining the relationship between vitamin D and PD have shown inconsistent and often conflicting findings, one of the most consistent findings is an inverse relationship between vitamin D levels and severity of motor symptoms.15 Other consistent findings are that serum levels of vitamin D are significantly lower in patients with overt PD than in patients without PD, and that serum vitamin D levels progressively decrease with increasing severity of PD.16,17 However, it is unclear whether these associations are linked to reduced mobility and decreased sun exposure as Parkinson disease progresses.15

Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis is a fatal disease of neurodegeneration, with a prognosis of a 3- to 5-year life expectancy after diagnosis.18 The disease is characterized by a progressive loss of motor neurons and is linked to glutamate neurotransmitter abnormalities.18 Although several proteins linking vitamin D to ALS pathology have been identified in genetic studies, evidence supporting a causative role is weak.18,19

In a systematic review and meta-analysis of 24 studies, Lanznaster et al found that ALS patients had slightly lower levels of vitamin D than healthy patients in the control group but could not find evidence supporting the role of vitamin D on ALS diagnosis, prognosis, or treatment.”18 Key limitations of studies on this topic are a lack of consideration of confounding factors.18

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Establishing a clinical correlation between vitamin D deficiency and neurologic disorders is difficult given the lack of longitudinal randomized controlled trials. It is unclear whether low vitamin D levels found in patients with these disorders are causative or are the result of confounding factors linked to underlying disease processes and associated disability.20 However, current evidence supports a link between MS and areas with higher rates of vitamin D deficiency, and the use of vitamin D supplementation to help slow cognitive decline in AD and reduce PD symptom severity.1,3

Researchers point to the need for rigorous clinical studies on vitamin D supplementation targeting disease-relevant endpoints. For disorders that do show improvement with vitamin D supplementation, alleviating symptoms or reducing the severity or disease expression can provide improvement in patient comfort and outcomes. Thus, treating vitamin D deficiency in patients with neurocognitive disorders to an endpoint of 50 ng/mL may be considered.1

Dana S. Miles, MS, PA-C, CAQ-EM, has been working in emergency medicine as a PA since 2005 and is currently in the Doctor of Medical Science (DMSc) program at A.T. Still University-Arizona School of Health Sciences.


1. Di Somma C, Scarano E, Barrea L, et al. Vitamin D and neurological diseases: an endocrine view. Int J Mol Sci. 2017;18(11):2482. doi:10.3390/ijms18112482

2. Bouillon R, Pike JW, Feldman D. Vitamin D. Volume 1: Biochemistry, Physiology and Diagnostics. 4th ed. Academic Press; 2018. Accessed February 17, 2022.

3. Pierrot-Deseilligny C, Souberbielle JC. Is hypovitaminosis D one of the environmental risk factors for multiple sclerosis? Brain. 2010;133(Pt 7):1869-88. doi:10.1093/brain/awq147

4. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53-58. doi:10.1210/jc.2010-2704

5. Feige J, Moser T, Bieler L, Schwenker K, Hauer L, Sellner J. Vitamin D supplementation in multiple sclerosis: a critical analysis of potentials and threats. Nutrients. 2020;12(3):783. doi:10.3390/nu12030783

6. Landel V, Annweiler C, Millet P, Morello M, Féron F. Vitamin D, cognition and Alzheimer disease: the therapeutic benefit is in the D-tails. J Alzheimers Dis. 2016;53(2):419-44. doi:10.3233/JAD-150943

7. Croll PH, Boelens M, Vernooij MW, et al. Associations of vitamin D deficiency with MRI markers of brain health in a community sample. Clin Nutr. 2021;40(1):72-78. doi:10.1016/j.clnu.2020.04.027.

8. Navale SS, Mulugeta A, Zhou A, Llewellyn DJ, Hyppönen E. Vitamin D and brain health: an observational and Mendelian randomization study. Am J Clin Nutr. 2022;116(2):531-540. doi:10.1093/ajcn/nqac107

9. 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. doi:10.1097/WNN.0b013e31826df647

10. Masoumi A, Goldenson B, Ghirmai S, et al. 1alpha,25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimer’s disease patients. J Alzheimers Dis. 2009;17(3):703-17. doi:10.3233/JAD-2009-1080

11. Mizwicki MT, Menegaz D, Zhang J, et al. Genomic and nongenomic signaling induced by 1α,25(OH)2-vitamin D3 promotes the recovery of amyloid-β phagocytosis by Alzheimer’s disease macrophages. J Alzheimers Dis. 2012;29(1):51-62. doi:10.3233/JAD-2012-110560

12. 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):1347-1352. doi:10.1136/jnnp-2018-320199

13. Laughlin GA, Kritz-Silverstein D, Bergstrom J, et al. Vitamin D insufficiency and cognitive function trajectories in older adults: the Rancho Bernardo Study. J Alzheimers Dis. 2017;58(3):871-883. doi:10.3233/JAD-161295

14. Mayne PE, Burne THJ. Vitamin D in synaptic plasticity, cognitive function, and neuropsychiatric illness. Trends Neurosci. 2019;42(4):293-306. doi:10.1016/j.tins.2019.01.003

15. Fullard ME, Duda JE. A review of the relationship between vitamin D and Parkinson disease symptoms. Front Neurol. 2020;11:454. doi:10.3389/fneur.2020.00454

16. Rimmelzwaan LM, van Schoor NM, Lips P, Berendse HW, Eekhoff EM. Systematic review of the relationship between vitamin D and Parkinson’s disease. J Parkinsons Dis. 2016;6(1):29-37. doi:10.3233/JPD-150615

17. Lv L, Tan X, Peng X, Bai R, Xiao Q, Zou T, Tan J, Zhang H, Wang C. The relationships of vitamin D, vitamin D receptor gene polymorphisms, and vitamin D supplementation with Parkinson’s disease. Transl Neurodegener. 2020;9(1):34. doi:10.1186/s40035-020-00213-2

18. Lanznaster D, Bejan-Angoulvant T, Gandía J, Blasco H, Corcia P. Is there a role for vitamin D in amyotrophic lateral sclerosis? A systematic review and meta-analysis. Front Neurol. 2020;11:697. doi:10.3389/fneur.2020.00697

19. Long Kv, Nguyễn LT. Roles of vitamin D in amyotrophic lateral sclerosis: possible genetic and cellular signaling mechanisms. Mol Brain. 2013 9;6:16. doi:10.1186/1756-6606-6-16.

20. Smolders J, Hiller A, Camu W. Editorial: vitamin D in neurological diseases: from pathophysiology to therapy. Front Neurol. 2021;12:614900. doi:10.3389/fneur.2021.614900