Effects of Combined Vestibular Rehabilitation and 25-Hydroxyvitamin D Supplementation on Vestibular Function in Patients with Vestibular Neuritis: A Randomized Controlled Trial
-
Mohammad Akbar Fayaz
,
Mansoureh Adel Ghahraman
,
Elham Tavanai
,
Kazem Malmir
,
Nasrin Yazdani
,
Akram Farahani
,
Mohammad Amin Safari
Abstract
Background and Aim: Inflammatory processes play a key role in vestibular neuritis (VN) pathogenesis, and recent research has associated vitamin D deficiency with various audio-vestibular conditions, including reduced serum 25-hydroxyvitamin D [25(OH)D] concentrations in individuals with acute VN. Given its notable immunomodulatory and anti-inflammatory actions, vitamin D may serve as an adjunct to enhance VRT outcomes. The present study examined the impact of combining 25(OH)D supplementation with VRT on vestibular function among patients with VN.
Methods: In this randomized controlled trial, 41 patients with VN were allocated into two groups. The VRT group (n=20) received individualized vestibular rehabilitation for 30 minutes, three times daily for 12 weeks. The VRT+VitD group (n=21) received the same VRT protocol plus a weekly oral dose of 50,000 IU of 25(OH)D for 12 weeks. Outcomes were assessed pre- and post-intervention using the Dizziness Handicap Inventory (DHI), Vertigo Symptom Scale-short form (VSS-sf), and affected canal vestibulo-ocular reflex gains with video head impulse test, within- and between-groups.
Results: Both groups improved significantly across all measurements. The VRT+VitD group showed a normal serum level of vitamin D post-intervention (39.36±3.06; p<0.001) and greater improvements in subjective symptom reduction (DHI; p=0.023; partial η²=0.126), and VOR gains (p<0.001 with partial η²=0.459, 0.576, and 0.197 for lateral, anterior, and posterior canals, respectively) compared to the VRT group.
Conclusion: Correcting vitamin D deficiency supports and potentially enhances the effects of vestibular rehabilitation in patients with vestibular neuritis, although these outcomes should be interpreted with caution due to the study’s limitations.
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7. Heinrichs N, Edler C, Eskens S, Mielczarek MM, Moschner C. Predicting continued dizziness after an acute peripheral vestibular disorder. Psychosom Med. 2007;69(7):700-7. [DOI:10.1097/PSY.0b013e318151a4dd]
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11. Tokle G, Mørkved S, Bråthen G, Goplen FK, Salvesen Ø, Arnesen H, et al. Efficacy of Vestibular Rehabilitation Following Acute Vestibular Neuritis: A Randomized Controlled Trial. Otol Neurotol. 2020;41(1):78-85. [DOI:10.1097/MAO.0000000000002443]
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13. Yoo MH, Yang CJ, Kim SA, Park MJ, Ahn JH, Chung JW, et al. Efficacy of steroid therapy based on symptomatic and functional improvement in patients with vestibular neuritis: a prospective randomized controlled trial. Eur Arch Otorhinolaryngol. 2017;274(6):2443-51. [DOI:10.1007/s00405-017-4556-1]
14. Greco A, Macri GF, Gallo A, Fusconi M, De Virgilio A, Pagliuca G, et al. Is vestibular neuritis an immune related vestibular neuropathy inducing vertigo? J Immunol Res. 2014;2014:459048. [DOI:10.1155/2014/459048]
15. Klokman VW, Verhagen MJJ, Sanders MS, Jellema K, de Kleijn DPV, Jie KE. Blood Biomarkers for the Diagnosis of Peripheral Causes of Vestibular Syndrome: A Systematic Review and Meta-Analysis. Otol Neurotol. 2025;46(9):e359-69. [DOI:10.1097/MAO.0000000000004608]
16. Wu Y, Hu Z, Cai M, Fan Z, Han W, Guan Q, et al. Decreased 25-Hydroxyvitamin D Levels in Patients With Vestibular Neuritis. Front Neurol. 2019;10:863. [DOI:10.3389/fneur.2019.00863]
17. Xiong S, Chen G, Chen Y, Xu T, Zhou L, Zhang H. [Serum 25-hydroxyvitamin D expression and its correlation in patients with vestibular neuritis]. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2022;36(8):607-12. Chinese. [DOI:10.13201/j.issn.2096-7993.2022.08.008]
18. Chen J, Zhang S, Cui K, Liu C. Risk factors for benign paroxysmal positional vertigo recurrence: a systematic review and meta-analysis. J Neurol. 2021;268(11):4117-27. [DOI:10.1007/s00415-020-10175-0]
19. Yang B, Lu Y, Xing D, Zhong W, Tang Q, Liu J, et al. Association between serum vitamin D levels and benign paroxysmal positional vertigo: a systematic review and meta-analysis of observational studies. Eur Arch Otorhinolaryngol. 2020;277(1):169-77. [DOI:10.1007/s00405-019-05694-0]
20. Bakhshaee M, Moradi S, Mohebi M, Ghayour-Mobarhan M, Sharifan P, Yousefi R, et al. Association Between Serum Vitamin D Level and Ménière's Disease. Otolaryngol Head Neck Surg. 2022;166(1):146-50. [DOI:10.1177/01945998211000395]
21. Huang X, Chua KW, Moh SPS, Yuen HW, Low DYM, Anaikatti P, et al. Falls and physical function in older patients with Benign Paroxysmal Positional Vertigo (BPPV): findings from a placebo controlled, double blinded randomized control trial (RCT) investigating efficacy of vitamin D treatment in lowering the recurrence rate of BPPV. Aging Clin Exp Res. 2025;37(1):43. [DOI:10.1007/s40520-025-02938-4]
22. Sheikhzadeh M, Lotfi Y, Mousavi A, Heidari B, Bakhshi E. The effect of serum vitamin D normalization in preventing recurrences of benign paroxysmal positional vertigo: A case-control study. Caspian J Intern Med. 2016;7(3):173-7.
23. Büki B, Jünger H, Lundberg YW. Vitamin D supplementation may improve symptoms in Meniere's disease. Med Hypotheses. 2018;116:44-6. [DOI:10.1016/j.mehy.2018.04.019]
24. Schwalfenberg GK. A review of the critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D deficiency. Mol Nutr Food Res. 2011;55(1):96-108.
25. Wei R, Christakos S. Mechanisms Underlying the Regulation of Innate and Adaptive Immunity by Vitamin D. Nutrients. 2015;7(10):8251-60. [DOI:10.3390/nu7105392]
26. Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc. 2010;85(8):752-7; quiz 757-8. [DOI:10.4065/mcp.2010.0138]
27. Jafarzadeh S, Bahrami E, Pourbakht A, Jalaie S, Daneshi A. Validity and reliability of the Persian version of the dizziness handicap inventory. J Res Med Sci. 2014;19(8):769-75.
28. Kamalvand A, Ghahraman MA, Jalaie S. Development of the Persian version of the Vertigo Symptom Scale: Validity and reliability. J Res Med Sci. 2017;22:58. [DOI:10.4103/jrms.JRMS_996_16]
29. McGarvie LA, MacDougall HG, Halmagyi GM, Burgess AM, Weber KP, Curthoys IS. The Video Head Impulse Test (vHIT) of Semicircular Canal Function - Age-Dependent Normative Values of VOR Gain in Healthy Subjects. Front Neurol. 2015;6:154. [DOI:10.3389/fneur.2015.00154]
30. Colotta F, Jansson B, Bonelli F. Modulation of inflammatory and immune responses by vitamin D. J Autoimmun. 2017;85:78-97. [DOI:10.1016/j.jaut.2017.07.007]
31. Di Rosa M, Malaguarnera G, De Gregorio C, Palumbo M, Nunnari G, Malaguarnera L. Immuno-modulatory effects of vitamin D3 in human monocyte and macrophages. Cell Immunol. 2012;280(1):36-43. [DOI:10.1016/j.cellimm.2012.10.009]
32. Khoo AL, Chai LY, Koenen HJ, Sweep FC, Joosten I, Netea MG, et al. Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals. Clin Exp Immunol. 2011;164(1):72-9.
33. Calton EK, Keane KN, Soares MJ. The potential regulatory role of vitamin D in the bioenergetics of inflammation. Curr Opin Clin Nutr Metab Care. 2015;18(4):367-73.
34. Yamamoto E, Jørgensen TN. Immunological effects of vitamin D and their relations to autoimmunity. J Autoimmun. 2019;100:7-16. [DOI:10.1016/j.jaut.2019.03.002]
35. Minasyan A, Keisala T, Zou J, Zhang Y, Toppila E, Syvälä H, et al. Vestibular dysfunction in vitamin D receptor mutant mice. J Steroid Biochem Mol Biol. 2009;114(3-5):161-6. [DOI:10.1016/j.jsbmb.2009.01.020]
36. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014;21(3):319-29. [DOI:10.1016/j.chembiol.2013.12.016]
37. Fishman JM, Burgess C, Waddell A. Corticosteroids for the treatment of idiopathic acute vestibular dysfunction (vestibular neuritis). Cochrane Database Syst Rev. 2011;2011(5):CD008607. [DOI:10.1002/14651858.CD008607.pub2]
38. Neve A, Corrado A, Cantatore FP. Immunomodulatory effects of vitamin D in peripheral blood monocyte-derived macrophages from patients with rheumatoid arthritis. Clin Exp Med. 2014;14(3):275-83. [DOI:10.1007/s10238-013-0249-2]
2. Sekitani T, Imate Y, Noguchi T, Inokuma T. Vestibular neuronitis: epidemiological survey by questionnaire in Japan. Acta Otolaryngol Suppl. 1993;503:9-12. [DOI:10.3109/00016489309128061]
3. Hülse R, Biesdorf A, Hörmann K, Stuck B, Erhart M, Hülse M, et al. Peripheral Vestibular Disorders: An Epidemiologic Survey in 70 Million Individuals. Otol Neurotol. 2019;40(1):88-95.
4. Adamec I, Krbot Skorić M, Handžić J, Habek M. Incidence, seasonality and comorbidity in vestibular neuritis. Neurol Sci. 2015;36(1):91-5. [DOI:10.1007/s10072-014-1912-4]
5. Bisdorff AR, Staab JP, Newman-Toker DE. Overview of the International Classification of Vestibular Disorders. Neurol Clin. 2015;33(3):541-50, vii. [DOI:10.1016/j.ncl.2015.04.010]
6. Bergenius J, Perols O. Vestibular neuritis: a follow-up study. Acta Otolaryngol. 1999;119(8):895-9. [DOI:10.1080/00016489950180243]
7. Heinrichs N, Edler C, Eskens S, Mielczarek MM, Moschner C. Predicting continued dizziness after an acute peripheral vestibular disorder. Psychosom Med. 2007;69(7):700-7. [DOI:10.1097/PSY.0b013e318151a4dd]
8. Bae CH, Na HG, Choi YS. Current diagnosis and treatment of vestibular neuritis: a narrative review. J Yeungnam Med Sci. 2022;39(2):81-8. [DOI:10.12701/yujm.2021.01228]
9. Huang HH, Chen CC, Lee HH, Chen HC, Lee TY, Tam KW, et al. Efficacy of Vestibular Rehabilitation in Vestibular Neuritis: A Systematic Review and Meta-analysis. Am J Phys Med Rehabil. 2024;103(1):38-46. [DOI:10.1097/PHM.0000000000002301]
10. McDonnell MN, Hillier SL. Vestibular rehabilitation for unilateral peripheral vestibular dysfunction. Cochrane Database Syst Rev. 2015;1(1):CD005397. [DOI:10.1002/14651858.CD005397.pub4]
11. Tokle G, Mørkved S, Bråthen G, Goplen FK, Salvesen Ø, Arnesen H, et al. Efficacy of Vestibular Rehabilitation Following Acute Vestibular Neuritis: A Randomized Controlled Trial. Otol Neurotol. 2020;41(1):78-85. [DOI:10.1097/MAO.0000000000002443]
12. Goudakos JK, Markou KD, Psillas G, Vital V, Tsaligopoulos M. Corticosteroids and vestibular exercises in vestibular neuritis. Single-blind randomized clinical trial. JAMA Otolaryngol Head Neck Surg. 2014;140(5):434-40. [DOI:10.1001/jamaoto.2014.48]
13. Yoo MH, Yang CJ, Kim SA, Park MJ, Ahn JH, Chung JW, et al. Efficacy of steroid therapy based on symptomatic and functional improvement in patients with vestibular neuritis: a prospective randomized controlled trial. Eur Arch Otorhinolaryngol. 2017;274(6):2443-51. [DOI:10.1007/s00405-017-4556-1]
14. Greco A, Macri GF, Gallo A, Fusconi M, De Virgilio A, Pagliuca G, et al. Is vestibular neuritis an immune related vestibular neuropathy inducing vertigo? J Immunol Res. 2014;2014:459048. [DOI:10.1155/2014/459048]
15. Klokman VW, Verhagen MJJ, Sanders MS, Jellema K, de Kleijn DPV, Jie KE. Blood Biomarkers for the Diagnosis of Peripheral Causes of Vestibular Syndrome: A Systematic Review and Meta-Analysis. Otol Neurotol. 2025;46(9):e359-69. [DOI:10.1097/MAO.0000000000004608]
16. Wu Y, Hu Z, Cai M, Fan Z, Han W, Guan Q, et al. Decreased 25-Hydroxyvitamin D Levels in Patients With Vestibular Neuritis. Front Neurol. 2019;10:863. [DOI:10.3389/fneur.2019.00863]
17. Xiong S, Chen G, Chen Y, Xu T, Zhou L, Zhang H. [Serum 25-hydroxyvitamin D expression and its correlation in patients with vestibular neuritis]. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2022;36(8):607-12. Chinese. [DOI:10.13201/j.issn.2096-7993.2022.08.008]
18. Chen J, Zhang S, Cui K, Liu C. Risk factors for benign paroxysmal positional vertigo recurrence: a systematic review and meta-analysis. J Neurol. 2021;268(11):4117-27. [DOI:10.1007/s00415-020-10175-0]
19. Yang B, Lu Y, Xing D, Zhong W, Tang Q, Liu J, et al. Association between serum vitamin D levels and benign paroxysmal positional vertigo: a systematic review and meta-analysis of observational studies. Eur Arch Otorhinolaryngol. 2020;277(1):169-77. [DOI:10.1007/s00405-019-05694-0]
20. Bakhshaee M, Moradi S, Mohebi M, Ghayour-Mobarhan M, Sharifan P, Yousefi R, et al. Association Between Serum Vitamin D Level and Ménière's Disease. Otolaryngol Head Neck Surg. 2022;166(1):146-50. [DOI:10.1177/01945998211000395]
21. Huang X, Chua KW, Moh SPS, Yuen HW, Low DYM, Anaikatti P, et al. Falls and physical function in older patients with Benign Paroxysmal Positional Vertigo (BPPV): findings from a placebo controlled, double blinded randomized control trial (RCT) investigating efficacy of vitamin D treatment in lowering the recurrence rate of BPPV. Aging Clin Exp Res. 2025;37(1):43. [DOI:10.1007/s40520-025-02938-4]
22. Sheikhzadeh M, Lotfi Y, Mousavi A, Heidari B, Bakhshi E. The effect of serum vitamin D normalization in preventing recurrences of benign paroxysmal positional vertigo: A case-control study. Caspian J Intern Med. 2016;7(3):173-7.
23. Büki B, Jünger H, Lundberg YW. Vitamin D supplementation may improve symptoms in Meniere's disease. Med Hypotheses. 2018;116:44-6. [DOI:10.1016/j.mehy.2018.04.019]
24. Schwalfenberg GK. A review of the critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D deficiency. Mol Nutr Food Res. 2011;55(1):96-108.
25. Wei R, Christakos S. Mechanisms Underlying the Regulation of Innate and Adaptive Immunity by Vitamin D. Nutrients. 2015;7(10):8251-60. [DOI:10.3390/nu7105392]
26. Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc. 2010;85(8):752-7; quiz 757-8. [DOI:10.4065/mcp.2010.0138]
27. Jafarzadeh S, Bahrami E, Pourbakht A, Jalaie S, Daneshi A. Validity and reliability of the Persian version of the dizziness handicap inventory. J Res Med Sci. 2014;19(8):769-75.
28. Kamalvand A, Ghahraman MA, Jalaie S. Development of the Persian version of the Vertigo Symptom Scale: Validity and reliability. J Res Med Sci. 2017;22:58. [DOI:10.4103/jrms.JRMS_996_16]
29. McGarvie LA, MacDougall HG, Halmagyi GM, Burgess AM, Weber KP, Curthoys IS. The Video Head Impulse Test (vHIT) of Semicircular Canal Function - Age-Dependent Normative Values of VOR Gain in Healthy Subjects. Front Neurol. 2015;6:154. [DOI:10.3389/fneur.2015.00154]
30. Colotta F, Jansson B, Bonelli F. Modulation of inflammatory and immune responses by vitamin D. J Autoimmun. 2017;85:78-97. [DOI:10.1016/j.jaut.2017.07.007]
31. Di Rosa M, Malaguarnera G, De Gregorio C, Palumbo M, Nunnari G, Malaguarnera L. Immuno-modulatory effects of vitamin D3 in human monocyte and macrophages. Cell Immunol. 2012;280(1):36-43. [DOI:10.1016/j.cellimm.2012.10.009]
32. Khoo AL, Chai LY, Koenen HJ, Sweep FC, Joosten I, Netea MG, et al. Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals. Clin Exp Immunol. 2011;164(1):72-9.
33. Calton EK, Keane KN, Soares MJ. The potential regulatory role of vitamin D in the bioenergetics of inflammation. Curr Opin Clin Nutr Metab Care. 2015;18(4):367-73.
34. Yamamoto E, Jørgensen TN. Immunological effects of vitamin D and their relations to autoimmunity. J Autoimmun. 2019;100:7-16. [DOI:10.1016/j.jaut.2019.03.002]
35. Minasyan A, Keisala T, Zou J, Zhang Y, Toppila E, Syvälä H, et al. Vestibular dysfunction in vitamin D receptor mutant mice. J Steroid Biochem Mol Biol. 2009;114(3-5):161-6. [DOI:10.1016/j.jsbmb.2009.01.020]
36. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014;21(3):319-29. [DOI:10.1016/j.chembiol.2013.12.016]
37. Fishman JM, Burgess C, Waddell A. Corticosteroids for the treatment of idiopathic acute vestibular dysfunction (vestibular neuritis). Cochrane Database Syst Rev. 2011;2011(5):CD008607. [DOI:10.1002/14651858.CD008607.pub2]
38. Neve A, Corrado A, Cantatore FP. Immunomodulatory effects of vitamin D in peripheral blood monocyte-derived macrophages from patients with rheumatoid arthritis. Clin Exp Med. 2014;14(3):275-83. [DOI:10.1007/s10238-013-0249-2]
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How to Cite
1.
Fayaz MA, Adel Ghahraman M, Tavanai E, Malmir K, Yazdani N, Farahani A, Safari MA. Effects of Combined Vestibular Rehabilitation and 25-Hydroxyvitamin D Supplementation on Vestibular Function in Patients with Vestibular Neuritis: A Randomized Controlled Trial. Aud Vestib Res. 2026;.
