Document Type : Original Article


1 Skull Base Research Center, Loghman Hakim Hospital Complex, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Brain Mapping Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Anesthesiology Research Center, Loghman Hakim Hospital Complex, Shahid Beheshti University of Medical Sciences, Tehran, Iran


Background: Clinical studies have reported improved neurological outcomes in patients who were taking vitamin D supplements. This study investigates the effect of intramuscular (IM) vitamin D supplementation in patients with acute ischemic stroke (AIS) on neurological outcomes and inflammatory marker levels.
Methods: This study included patients diagnosed with AIS (n = 60) from the Neurology Unit of Loghman Hakim Hospital, Tehran, Iran, during the year 2019. Patients with AIS were allocated randomly into two groups who received a single dose of 300000 IU IM vitamin D and a control group that did not receive vitamin D supplementation. Serum vitamin D concentration, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels, as primary outcomes, and the Modified Rankin Scale (MRS), the National Institute of Health Stroke Scale (NIHSS), and the Mini-Mental State Examination (MMSE), as secondary outcomes, were measured at the baseline and the end of the study (6 weeks).
Results: Eventually, 59 patients with AIS completed the intervention study. A single dose of 300000 IU increased vitamin D level; moreover, vitamin D supplementation improved MRS and IL-6 levels significantly (P = 0.01, P = 0.02, respectively). There were reverse correlations between serum vitamin D and NIHSS and TNF-α after vitamin D administration. However, no statistically significant effect of vitamin D on the TNF-α or NIHSS and MMSE was seen compared to the control group.
Conclusion: Vitamin D probably due to a single dose and short duration of administration, as well as a short follow-up period, had no favorable effects on TNF-α level and NIHSS score.


  1. Qiu H, Wang M, Mi D, Zhao J, Tu W, Liu Q. Vitamin D status and the risk of recurrent stroke and mortality in ischemic stroke patients: Data from a 24-month follow-up study in China. J Nutr Health Aging 2017; 21(7): 766-71.
  2. Liu H, Wang J, Xu Z. Prognostic utility of serum 25-hydroxyvitamin D in patients with stroke: A meta-analysis. J Neurol 2020; 267(11): 3177-86.
  3. Nie Z, Ji XC, Wang J, Zhang HX. Serum levels of 25-hydroxyvitamin D predicts infarct volume and mortality in ischemic stroke patients. J Neuroimmunol 2017; 313: 41-5.
  4. Wajda J, Swiat M, Owczarek AJ, Brzozowska A, Olszanecka-Glinianowicz M, Chudek J. Severity of vitamin D deficiency predicts mortality in ischemic stroke patients. Dis Markers 2019; 2019: 3652894.
  5. Park KY, Chung PW, Kim YB, Moon HS, Suh BC, Won YS, et al. Serum vitamin D status as a predictor of prognosis in patients with acute ischemic stroke. Cerebrovasc Dis 2015; 40(1-2): 73-80.
  6. Calton EK, Keane KN, Newsholme P, Soares MJ. The impact of vitamin D levels on inflammatory status: A systematic review of immune cell studies. PLoS One 2015; 10(11): e0141770.
  7. Wang Y, Chiang YH, Su TP, Hayashi T, Morales M, Hoffer BJ, et al. Vitamin D(3) attenuates cortical infarction induced by middle cerebral arterial ligation in rats. Neuropharmacology 2000; 39(5): 873-80.
  8. Grant WB. Does vitamin D reduce the risk of dementia? J Alzheimers Dis 2009; 17(1): 151-9.
  9. Chen H, Liu Y, Huang G, Zhu J, Feng W, He J. Association between vitamin D status and cognitive impairment in acute ischemic stroke patients: A prospective cohort study. Clin Interv Aging 2018; 13: 2503-9.
  10. Zhou R, Wang M, Huang H, Li W, Hu Y, Wu T. Lower vitamin D status is associated with an increased risk of ischemic stroke: A systematic review and meta-analysis. Nutrients 2018; 10(3): 277.
  11. Narasimhan S, Balasubramanian P. Role of vitamin D in the outcome of ischemic stroke- a randomized controlled trial. J Clin Diagn Res 2017; 11(2): CC06-CC10.
  12. Momosaki R, Abo M, Urashima M. Vitamin D Supplementation and post-stroke rehabilitation: A randomized, double-blind, placebo-controlled trial. Nutrients 2019; 11(6): 1295.
  13. Dawson-Hughes B. Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment. UpToDate [Online]. [cited Feb 2021]; Available from: URL:
  14. Marniemi J, Alanen E, Impivaara O, Seppanen R, Hakala P, Rajala T, et al. Dietary and serum vitamins and minerals as predictors of myocardial infarction and stroke in elderly subjects. Nutr Metab Cardiovasc Dis 2005; 15(3): 188-97.
  15. Daubail B, Jacquin A, Guilland JC, Hervieu M, Osseby GV, Rouaud O, et al. Serum 25-hydroxyvitamin D predicts severity and prognosis in stroke patients. Eur J Neurol 2013; 20(1): 57-61.
  16. Mpandzou G, Ait 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.
  17. Wang Q, Zhu Z, Liu Y, Tu X, He J. Relationship between serum vitamin D levels and inflammatory markers in acute stroke patients. Brain Behav 2018; 8(2): e00885.
  18. Kim K, Cho KH, Im SH, Choi J, Yu J, Kim M. Decrement of serum vitamin D level after stroke. Ann Rehabil Med 2017; 41(6): 944-50.
  19. Kajta M, Makarewicz D, Zieminska E, Jantas D, Domin H, Lason W, et al. Neuroprotection by co-treatment and post-treating with calcitriol following the ischemic and excitotoxic insult in vivo and in vitro. Neurochem Int 2009; 55(5): 265-74.
  20. Oermann E, Bidmon HJ, Witte OW, Zilles K. Effects of 1alpha,25 dihydroxyvitamin D3 on the expression of HO-1 and GFAP in glial cells of the photothrombotically lesioned cerebral cortex. J Chem Neuroanat 2004; 28(4): 225-38.
  21. Losem-Heinrichs E, Gorg B, Redecker C, Schleicher A, Witte OW, Zilles K, et al. 1alpha,25-dihydroxy-vitamin D3 in combination with 17beta-estradiol lowers the cortical expression of heat shock protein-27 following experimentally induced focal cortical ischemia in rats. Arch Biochem Biophys 2005; 439(1): 70-9.
  22. Pilz S, Tomaschitz A, Drechsler C, Zittermann A, Dekker JM, Marz W. Vitamin D supplementation: A promising approach for the prevention and treatment of strokes. Curr Drug Targets 2011; 12(1): 88-96.
  23. Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: A double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2006; 83(4): 754-9.
  24. Matthews LR, Ahmed Y, Wilson KL, Griggs DD, Danner OK. Worsening severity of vitamin D deficiency is associated with increased length of stay, surgical intensive care unit cost, and mortality rate in surgical intensive care unit patients. Am J Surg 2012; 204(1): 37-43.
  25. Witham MD, Dove FJ, Sugden JA, Doney AS, Struthers AD. The effect of vitamin D replacement on markers of vascular health in stroke patients - a randomised controlled trial. Nutr Metab Cardiovasc Dis 2012; 22(10): 864-70.
  26. Thomas T, Briot K. Vitamin D: Skeletal and muscular effects. Presse Med 2013; 42(10): 1351-7.
  27. Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P, et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation 2007; 115(7): 846-54.
  28. Wang Y, Ji H, Tong Y, Zhang ZB. Prognostic value of serum 25-hydroxyvitamin D in patients with stroke. Neurochem Res 2014; 39(7): 1332-7.