Journal of Neurology Research, ISSN 1923-2845 print, 1923-2853 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Neurol Res and Elmer Press Inc
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Original Article

Volume 16, Number 1, March 2026, pages 30-39


The Role of Calcitriol (Vitamin D) as Neuroprotection and Prognostic Biomarker in Patients With Ischemic and Hemorrhagic Stroke

Figures

↓  ↓  Figure 1. Flow diagram of the study selection process for articles included in the systematic review and meta-analysis.
Figure 1.
↓  ↓  Figure 2. Risk of bias analysis. (a) Traffic-light plot of the risk of bias assessment using ROB-2, illustrating the bias risk results for the effect of vitamin D supplementation on neurological function improvement across each domain. (b) Overall risk of bias conclusion using ROB-2, summarizing the risk of bias regarding the effect of vitamin D supplementation on neurological function improvement. (c) Overall risk of bias conclusion using ROBINS-I, indicating the risk of bias for vitamin D levels as a prognostic biomarker in stroke severity. (d) Traffic-light plot of the risk of bias assessment using ROBINS-I, depicting the risk of bias for the analysis of vitamin D levels in stroke severity as a prognostic biomarker across each domain. ROB-2: risk of bias 2; ROBINS-I: risk of bias in non-randomized studies of interventions.
Figure 2.
↓  ↓  Figure 3. Analysis results. (a) Forest plot showing the effect of vitamin D supplementation on neurological function improvement compared to the control group. (b) Forest plot analyzing vitamin D levels in relation to stroke severity as a prognostic biomarker.
Figure 3.

Tables

↓  Table 1. Characteristics of Study Data on Primary Outcome (Effect of Vitamin D Supplementation on Neurological Function Improvement)
 
No. Author Location Sample size Study design Diagnosis Intervention regimen Control regimen Outcome measurement tools
1. Acharya et al, 2022 India 325 Randomized controlled trial Ischemic stroke and hemorrhagic stroke Single intramuscular dose of 600,000 International Units (IU) of vitamin D Vitamin D not administered Scandinavian Stroke Scale (SSS) score
2. Hesami et al, 2022 Iran 570 Randomized controlled trial Ischemic stroke Single intramuscular dose of 600,000 IU of vitamin D3 Vitamin D not administered The Neuron-Specific Enolase (NSE) level, the National Institutes of Health Stroke Scale (NIHSS), and Barthel Index (BI)
3. Karasu et al, 2021 Turkey 76 Retrospective Ischemic stroke and hemorrhagic stroke Weekly oral dose of 50,000 IU for 4–12 weeks, with a total dose ranging from 200,000 to 600,000 IU Vitamin D not administered Brunnstrom Recovery Stage and Functional Ambulation Classification (FAC) score
4. Rezaei et al, 2021 Iran 60 Randomized controlled trial Ischemic stroke Single intramuscular dose of 300,000 IU of vitamin D Vitamin D not administered NIHSS, modified Rankin Scale (mRS), and the Mini-Mental State Examination (MMSE)
5. Torrisi et al, 2021 Italy 40 Randomized controlled trial Ischemic stroke and hemorrhagic stroke Daily oral dose of 2,000 IU/day of vitamin D3 for 12 weeks Vitamin D not administered Montgomery-Aasberg Depression Rating Scale (MADRS) and Functional Independent Measures (FIM)
6. Narasimhan et al, 2017 India 60 Randomized controlled trial Ischemic stroke Single intramuscular dose of 600,000 IU of vitamin D3 Vitamin D not administered SSS score
7. Sari et al, 2018 Turkey 64 Randomized controlled trial Ischemic stroke Single intramuscular dose of 300,000 IU of vitamin D Vitamin D not administered Brunnstrom Recovery Staging (BRS), Functional Ambulation Scale (FAS), Modified Barthel Index (MBI) scores, and Berg Balance Scale (BBS)

 

↓  Table 2. Characteristics of Study Data on Secondary Outcome (Analysis of Vitamin D Levels in Stroke Severity as a Prognostic Biomarker)
 
No. Author Location Sample size Study design Diagnosis Assessment of stroke severity Assessment of serum vitamin D levels
8. Afshari et al, 2015 Iran 72 Case-control Ischemic stroke Brain computed tomography Enzyme-linked immunosorbent assay (ELISA)
9. Aggarwal et al, 2022 India 200 One-year prospective observational Ischemic stroke The National Institutes of Health Stroke scale (NIHSS) and modified Rankin scale (mRS) Electrochemiluminescence (ECL) method
10. Alfieri et al, 2017 Brazil 286 Case-control Ischemic stroke mRS Chemiluminescent microparticle immunoassay (CMIA)
11. Borowicz et al, 2023 Poland 80 Randomized controlled trial Ischemic stroke NIHSS, mRS, and Barthel index (BI) CMIA
12. Rad et al, 2021 Iran 140 Bi-center cross-sectional Ischemic stroke and hemorrhagic Stroke NIHSS and mRS ECL
13. Samarakoon et al, 2024 Sri Lanka 60 Prospective case-control Ischemic stroke NIHSS and mRS ELISA
14. Selim et al, 2019 Egypt 138 Case-control Ischemic stroke and hemorrhagic stroke NIHSS and mRS ELISA
15. Simon et al, 2024 India 86 Prospective observational Ischemic stroke NIHSS Chemiluminescence immunoassay (CLIA)
16. Turetsky et al, 2015 United States 96 Retrospectively analyze prospective Ischemic stroke NIHSS and mRS CLIA
17. Wajda et al, 2019 Poland 240 Retrospective cohort study Ischemic stroke NIHSS and mRS ECL
18. Daubail et al, 2012 France 386 Observational cohort study Ischemic stroke and hemorrhagic stroke NIHSS and mRS High pressure liquid chromatography coupled with UV detection
19. Fahmy et al, 2019 Egypt 96 Case-control Ischemic stroke NIHSS and mRS ELISA
20. Kim et al, 2020 South Korea 328 Single-center retrospective study Ischemic stroke NIHSS Radioimmunoassay kit
21. Park et al, 2015 South Korea 818 Observational cohort retrospective Ischemic stroke NIHSS and mRS Liquid chromatography tandem mass spectrometry
22. Tu et al, 2014 China 364 Prospective cohort Ischemic stroke NIHSS and mRS Competitive chemiluminescent immunoassay on a calibrated Elecsys 2010
23. Wang et al, 2014 New York 326 Prospective cohort Ischemic stroke NIHSS and mRS The E601 modular (Roche Diagnostics, Mannheim, Germany) with a calibration range from 3 to 70 ng/mL