Iranian Journal of Medical Sciences

Iranian Journal of Medical Sciences

Current Issue

By Issue

By Author

By Subject

Author Index

Keyword Index

About Journal

Aims and Scope

Journal Team

Publication Ethics

Indexing and Abstracting

Related Links

Peer Review Process

Journal Metrics

Investigating the Effect of High-Dose Vitamin D3 Administration on Inflammatory Biomarkers in Patients with Moderate to Severe Traumatic Brain Injury: A Randomized Clinical Trial

Document Type : Original Article(s)

Authors

1 Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Department of Pulmonary and Critical Care Medicine, Imam Hossein Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Department of Neurosurgery, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Department of Radiology, School of Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

5 Prevention of Cardiovascular Disease Research Center, Imam Hossein Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

6 Department of Pulmonary and Critical Care Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

7 Department of Pharmaceutical Care Unit, Imam Hossein Medical and Educational Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

10.30476/ijms.2023.99465.3156

Abstract

Background: Traumatic brain injury (TBI) is one of the most common neurological disorders worldwide. We aimed to investigate the efficacy of high-dose vitamin D3 on inflammatory biomarkers in patients with moderate to severe TBI. 
Methods: Thirty-five moderate to severe TBI patients were randomly assigned to intervention and control groups. Patients in the intervention group received a single intramuscular (IM) dose of 300,000 IU vitamin D. The primary endpoints were interleukin levels (IL-1β and IL-6), and the secondary endpoints were changes in neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), Glasgow Coma scale (GCS), and Glasgow Outcome Scale-Extended (GOS-E) scores compared between intervention and control arms of the study. The linear Generalized Estimating Equations were used for trend analysis and evaluating the association of independent factors to each outcome.
Results: The results revealed a significant decrease in IL-1β levels (-2.71±3.02, in the intervention group: P=0.001 vs. -0.14±3.70, in the control group: P=0.876) and IL-6 (-88.05±148.45, in the intervention group: P=0.0001 vs. -35.54±175.79, in the control group: P=0.325) 3 days after the intervention. The improvement in the GCS score (P=0.001), reduction in NLR (P=0.001) and PLR (P=0.002), and improvement in the GOS-E score (P=0.039) was found to be greater in the vitamin D3 arm of the study than the control group.
Conclusion: Administration of high-dose vitamin D3 in the acute phase of TBI could be effective in lowering the inflammatory markers and improving the level of consciousness and long-term performance outcomes.
Trial registration number: IRCT20180522039777N2.

Keywords

References
  1. Mollayeva T, Mollayeva S, Colantonio A. Traumatic brain injury: sex, gender and intersecting vulnerabilities. Nat Rev Neurol. 2018;14:711-22. doi: 10.1038/s41582-018-0091-y. PubMed PMID: 30397256.
  2. Peterson AB, Thomas KE, Zhou H. Surveillance Report of Traumatic Brain Injury-related Deaths by Age Group, Sex, and Mechanism of Injury—United States, 2018 and 2019. 2022.
  3. Maas AIR, Menon DK, Manley GT, Abrams M, Akerlund C, Andelic N, et al. Traumatic brain injury: progress and challenges in prevention, clinical care, and research. Lancet Neurol. 2022;21:1004-60. doi: 10.1016/S1474-4422(22)00309-X. PubMed PMID: 36183712; PubMed Central PMCID: PMCPMC10427240.
  4. Ghaith HS, Nawar AA, Gabra MD, Abdelrahman ME, Nafady MH, Bahbah EI, et al. A Literature Review of Traumatic Brain Injury Biomarkers. Mol Neurobiol. 2022;59:4141-58. doi: 10.1007/s12035-022-02822-6. PubMed PMID: 35499796; PubMed Central PMCID: PMCPMC9167167.
  5. Kadhim HJ, Duchateau J, Sebire G. Cytokines and brain injury: invited review. J Intensive Care Med. 2008;23:236-49. doi: 10.1177/0885066608318458. PubMed PMID: 18504260.
  6. Lucas SM, Rothwell NJ, Gibson RM. The role of inflammation in CNS injury and disease. Br J Pharmacol. 2006;147:S232-40. doi: 10.1038/sj.bjp.0706400. PubMed PMID: 16402109; PubMed Central PMCID: PMCPMC1760754.
  7. Lu KT, Wang YW, Yang JT, Yang YL, Chen HI. Effect of interleukin-1 on traumatic brain injury-induced damage to hippocampal neurons. J Neurotrauma. 2005;22:885-95. doi: 10.1089/neu.2005.22.885. PubMed PMID: 16083355.
  8. Sharma S, Kumar A, Choudhary A, Sharma S, Khurana L, Sharma N, et al. Neuroprotective Role of Oral Vitamin D Supplementation on Consciousness and Inflammatory Biomarkers in Determining Severity Outcome in Acute Traumatic Brain Injury Patients: A Double-Blind Randomized Clinical Trial. Clin Drug Investig. 2020;40:327-34. doi: 10.1007/s40261-020-00896-5. PubMed PMID: 32172522; PubMed Central PMCID: PMCPMC7224135.
  9. Li W, Deng W. Platelet-to-lymphocyte ratio predicts short-term mortality in patients with moderate to severe traumatic brain injury. Sci Rep. 2022;12:13976. doi: 10.1038/s41598-022-18242-4. PubMed PMID: 35978006; PubMed Central PMCID: PMCPMC9385644.
  10. Siwicka-Gieroba D, Malodobry K, Biernawska J, Robba C, Bohatyrewicz R, Rola R, et al. The Neutrophil/Lymphocyte Count Ratio Predicts Mortality in Severe Traumatic Brain Injury Patients. J Clin Med. 2019;8. doi: 10.3390/jcm8091453. PubMed PMID: 31547411; PubMed Central PMCID: PMCPMC6780814.
  11. Xu J, Li S, Lui KY, Song X, Hu X, Cao L, et al. The neutrophil-to-lymphocyte ratio: A potential predictor of poor prognosis in adult patients with trauma and traumatic brain injury. Front Surg. 2022;9:917172. doi: 10.3389/fsurg.2022.917172. PubMed PMID: 36081584; PubMed Central PMCID: PMCPMC9445209.
  12. Wilson JT, Pettigrew LE, Teasdale GM. Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma. 1998;15:573-85. doi: 10.1089/neu.1998.15.573. PubMed PMID: 9726257.
  13. Rubin ML, Yamal JM, Chan W, Robertson CS. Prognosis of Six-Month Glasgow Outcome Scale in Severe Traumatic Brain Injury Using Hospital Admission Characteristics, Injury Severity Characteristics, and Physiological Monitoring during the First Day Post-Injury. J Neurotrauma. 2019;36:2417-22. doi: 10.1089/neu.2018.6217. PubMed PMID: 30860434; PubMed Central PMCID: PMCPMC6661910.
  14. Ono J, Yamaura A, Kubota M, Okimura Y, Isobe K. Outcome prediction in severe head injury: analyses of clinical prognostic factors. J Clin Neurosci. 2001;8:120-3. doi: 10.1054/jocn.2000.0732. PubMed PMID: 11484659.
  15. Marshall LF, Marshall SB, Klauber MR, Clark MvB, Eisenberg HM, Jane JA, et al. A new classification of head injury based on computerized tomography. Journal of Neurosurgery. 1991;75:S14-S20. doi: https://doi.org/10.3171/sup.1991.75.1s.0s14.
  16. Maas AI, Hukkelhoven CW, Marshall LF, Steyerberg EW. Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and combinations of computed tomographic predictors. Neurosurgery. 2005;57:1173-82. doi: 10.1227/01.neu.0000186013.63046.6b. PubMed PMID: 16331165.
  17. Sistanizad M, Kouchek M, Miri M, Salarian S, Shojaei S, Moeini Vasegh F, et al. High dose vitamin D improves total serum antioxidant capacity and ICU outcome in critically ill patients - A randomized, double-blind clinical trial. European Journal of Integrative Medicine. 2021;42:101271. doi: https://doi.org/10.1016/j.eujim.2020.101271.
  18. Menger J, Lee ZY, Notz Q, Wallqvist J, Hasan MS, Elke G, et al. Administration of vitamin D and its metabolites in critically ill adult patients: an updated systematic review with meta-analysis of randomized controlled trials. Crit Care. 2022;26:268. doi: 10.1186/s13054-022-04139-1. PubMed PMID: 36068584; PubMed Central PMCID: PMCPMC9446655.
  19. Jamall OA, Feeney C, Zaw-Linn J, Malik A, Niemi ME, Tenorio-Jimenez C, et al. Prevalence and correlates of vitamin D deficiency in adults after traumatic brain injury. Clin Endocrinol (Oxf). 2016;85:636-44. doi: 10.1111/cen.13045. PubMed PMID: 26921561; PubMed Central PMCID: PMCPMC5053278.
  20. Viglianti EM, Zajic P, Iwashyna TJ, Amrein K. Neither vitamin D levels nor supplementation are associated with the development of persistent critical illness: a retrospective cohort analysis. Crit Care Resusc. 2019;21:39-44. PubMed PMID: 30857511; PubMed Central PMCID: PMCPMC6696918.
  21. Arabi SM, Sedaghat A, Ehsaei MR, Safarian M, Ranjbar G, Rezaee H, et al. Efficacy of high-dose versus low-dose vitamin D supplementation on serum levels of inflammatory factors and mortality rate in severe traumatic brain injury patients: study protocol for a randomized placebo-controlled trial. Trials. 2020;21:685. doi: 10.1186/s13063-020-04622-6. PubMed PMID: 32727558; PubMed Central PMCID: PMCPMC7388115.
  22. Lee JM, Jeong SW, Kim MY, Park JB, Kim MS. The Effect of Vitamin D Supplementation in Patients with Acute Traumatic Brain Injury. World Neurosurg. 2019;126:e1421-e6. doi: 10.1016/j.wneu.2019.02.244. PubMed PMID: 30904798.
  23. Cekic M, Sayeed I, Stein DG. Combination treatment with progesterone and vitamin D hormone may be more effective than monotherapy for nervous system injury and disease. Front Neuroendocrinol. 2009;30:158-72. doi: 10.1016/j.yfrne.2009.04.002. PubMed PMID: 19394357; PubMed Central PMCID: PMCPMC3025702.
  24. Hawryluk GWJ, Rubiano AM, Totten AM, O’Reilly C, Ullman JS, Bratton SL, et al. Guidelines for the Management of Severe Traumatic Brain Injury: 2020 Update of the Decompressive Craniectomy Recommendations. Neurosurgery. 2020;87:427-34. doi: 10.1093/neuros/nyaa278. PubMed PMID: 32761068; PubMed Central PMCID: PMCPMC7426189.
  25. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818-29. PubMed PMID: 3928249.
  26. Wilson L, Boase K, Nelson LD, Temkin NR, Giacino JT, Markowitz AJ, et al. A Manual for the Glasgow Outcome Scale-Extended Interview. J Neurotrauma. 2021;38:2435-46. doi: 10.1089/neu.2020.7527. PubMed PMID: 33740873; PubMed Central PMCID: PMCPMC8390784.
  27. Galea J, Ogungbenro K, Hulme S, Patel H, Scarth S, Hoadley M, et al. Reduction of inflammation after administration of interleukin-1 receptor antagonist following aneurysmal subarachnoid hemorrhage: results of the Subcutaneous Interleukin-1Ra in SAH (SCIL-SAH) study. J Neurosurg. 2018;128:515-23. doi: 10.3171/2016.9.JNS16615. PubMed PMID: 28298024.
  28. Bergold PJ. Treatment of traumatic brain injury with anti-inflammatory drugs. Exp Neurol. 2016;275:367-80. doi: 10.1016/j.expneurol.2015.05.024. PubMed PMID: 26112314; PubMed Central PMCID: PMCPMC6007860.
  29. Agh F, Mousavi SH, Aryaeian N, Amiri F, Jalilvand MR, Janani L, et al. Protective Effect of Vitamin D Supplementation on Some Hemogram Derived Inflammatory Indices in Normal and High-Fat Diet Fed Male Wistar Rats. Int J Prev Med. 2023;14:49. doi: 10.4103/ijpvm.ijpvm_505_20. PubMed PMID: 37351039; PubMed Central PMCID: PMCPMC10284218.
  30. Guan J, Karsy M, Brock AA, Eli IM, Manton GM, Ledyard HK, et al. Vitamin D status and 3-month Glasgow Outcome Scale scores in patients in neurocritical care: prospective analysis of 497 patients. J Neurosurg. 2018;128:1635-41. doi: 10.3171/2017.2.JNS163037. PubMed PMID: 28799870.
  31. Miri M, Kouchek M, Rahat Dahmardeh A, Sistanizad M. Effect of High-Dose Vitamin D on Duration of Mechanical Ventilation in ICU Patients. Iran J Pharm Res. 2019;18:1067-72. doi: 10.22037/ijpr.2019.1100647. PubMed PMID: 31531088; PubMed Central PMCID: PMCPMC6706749.
  32. Miroliaee AE, Salamzadeh J, Shokouhi S, Fatemi A, Ardehali SH, Hajiesmaeili MR, et al. Effect of Vitamin D Supplementation on Procalcitonin as Prognostic Biomarker in Patients with Ventilator Associated Pneumonia Complicated with Vitamin D Deficiency. Iran J Pharm Res. 2017;16:1254-63. PubMed PMID: 29201115; PubMed Central PMCID: PMCPMC5610782.
Iranian Journal of Medical Sciences

Articles InPress, Corrected Proof
Available Online from 24 February 2024
Files
History
  • Received: 25 July 2023
  • Revised: 19 October 2023
  • Accepted: 09 November 2023
Share
How to cite
Statistics