The Association between Serum Vitamin D Levels and Benign Paroxysmal Positional Vertigo

The Association Between Serum Vitamin D Levels and Benign Paroxysmal Positional Vertigo
Kanokporn Sarsitthithum, MD^1,2

, Tosapohn Wisupagan, MD¹, Sivaporn Kiatthanabumrung, MD¹, and Chanchai Jariengprasert, MD¹Ear, Nose & Throat Journal
2023, Vol. 102(7) 473–477
© The Author(s) 2021
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DOI: 10.1177/01455613211008561
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AbstractObjective: This study aimed to evaluate the association between serum vitamin D levels and benign paroxysmal positional vertigo (BPPV). Participants and Methods: This prospective study consisted of 137 participants. There were 69 participants in the BPPV group compared with 68 healthy participants. Blood samples from both groups were collected from all participants to assess serum vitamin D levels. Results: No significant difference in demographic data between BPPV and control groups. The results showed that the mean serum vitamin D levels in the BPPV group was lower than that of the control group (P value = .001). Among BPPV participants, there was no statistically significant difference between mean serum vitamin D levels of participants with recurrent BPPV, and that of newly diagnosed BPPV participants (P value = .313). Conclusion: A statistically significant association between lower mean serum vitamin D levels in the BPPV group compared with that of the control group. Therefore, low serum vitamin D levels may be one of the risk factors for BPPV.Keywordsbenign paroxysmal positional vertigo, BPPV, vitamin D, 25-hydroxyvitamin D, recurrenceIntroductionBenign paroxysmal positional vertigo (BPPV) is one of the most common peripheral vestibular diseases in vestibular clinics. The cumulative incidence is approximately 10% of the general population. Benign paroxysmal positional vertigo is characterized by transient vertigo or positional nystagmus provoked by head position change. The main treatment of this disease is rehabilitation therapy using canalith repositioning procedure, with a recurrent rate of approximately 50%.¹ Patients with BPPV have a lower quality of life compared to the general population.² A widely accepted cause of BPPV is the dislodgement of otoconia from the utricle into the semicircular canals. Several predisposing factors for BPPV have been reported, such as head trauma, advanced age, and gender being female.³ The definite cause of otoconia dislodgement in patients with idiopathic BPPV is not obviously known.Many studies have been reported about the relationship of low bone mineral density and patients with BPPV,^4-9 because bone and otoconia may degenerate in the same direction.^10,11 The primary function of vitamin D is directly related to calcium homeostasis and bone formation. Several studies of the relationship between calcium homeostasis or serum vitamin D levels and BPPV have concluded that low serum vitamin D levels are related to the BPPV or recurrent BPPV.^6,12-14 There are also a number of studies regarding the treatment of vitamin D deficiency in patients with BPPV. These studies have concluded that normalization of serum vitamin D levels can reduce the recurrent rate of BPPV.^15,16However, some studies showed no significant relationship between BPPV and vitamin D deficiency.^17-19 Past studies have not been able to conclude that serum vitamin D levels and the pathogenesis of BPPV are associated. That is probably due to the limitations of those studies. There are many factors that can affect serum vitamin D levels, such as gender, ethnicity, latitude, habitat, weather seasons, body weight, or even different dietary characteristics. The objective of this study is to study the relationship between serum vitamin D levels in patients with BPPV, which have not been studied in Thailand with latitude, season, and dietary characteristics that are different from previous studies. Therefore, there may be differences in serum vitamin D levels in the study population. This study is to examine the relationship between serum vitamin D levels and BPPV in Thai patients, which may be useful for preventing the occurrence of BPPV or recurrent BPPV in the future.Materials and MethodsParticipantsThis study was a prospective cross-sectional study conducted in the otolaryngology department of Ramathibodi hospital between May 1, 2018, to April 30, 2019. The research had been conducted after being approved by the Human Ethics Committees at Ramathibodi hospital. A total of 137 participants were divided into a BPPV group and a control group.The BPPV group included 69 patients. The inclusion criteria of the BPPV group were (1) patients diagnosed with idiopathic BPPV according to the criteria of von Brevern et al,¹ (2) patients aged 18 years or above, (3) patients who agree to participate in the research project by signing the informed consent after receiving the detailed explanation of the research project. The exclusion criteria were (1) patients with factors affecting the occurrence of BPPV disease, such as having a history of head injury or having a history of inner ear surgery, (2) patients with conditions that affect the calcium metabolism, such as endocrine disorder, parathyroid hormone-related disease, malignancy-related disease, chronic kidney disease, on medication-related calcium metabolism, and so on.The BPPV group was divided into 2 subgroups which were the first diagnosis of BPPV group and the recurrent BPPV group. The definition of recurrent BPPV was the occurrence of vertigo after a complete recovery 1 month or more.¹² We confirm complete recovery when patients exhibit no clinical symptoms of vertigo and no positional nystagmus in the follow-up.The control group included 68 volunteers. Inclusion criteria of the control group were (1) people aged 18 years or above, (2) people who agree to participate in the research project by signing the informed consent after receiving the detailed explanation of the research project, and (3) people with no history of dizziness or vertigo within 2 years.MethodsMeasurement of serum vitamin D levels. All participants’ blood was collected to measure 25-OH vitamin D total levels by using chemiluminescent immunoassay technology (LIAISON1 25-OH vitamin D total assay). For the BPPV group, a blood test was done within 7 days after diagnosed with BPPV or recurrent BPPV. If hemolysis occured more than+3, a new blood test was done because it affects vitamin D measurement.Tab1To analyze the data of the participants from the comparison of mean 25-OH vitamin D total in blood between patients with BPPV and volunteers by defining vitamin D deficiency is a 25-OH vitamin D total level < 20 ng/mL, vitamin D insufficiency is defined as a 25-OH vitamin D total level 21 to 29 ng/mL, and vitamin D sufficiency is defined as a 25-OH vitamin D total level > 30 ng/mL.²⁰Statistical analysis method. The data calculated using the STATA 15.1 with P value <.05 is considered statistically significant. The descriptive statistics included mean, standard deviation, percent (%) by using independent t test for the continuous data comparison, and ϰ² test for the group data comparison.ResultsA total of 137 participants were divided into 69 patients of the BPPV group and 68 volunteers of the control group. Within the BPPV group, it was divided into subgroups which were the first diagnosis of BPPV group in the number of 28 patients and the recurrent BPPV group in the number of 41 patients.The BPPV group consisted of 10 males (14.5%) and 59 females (85.5%). The age of this group was between 39 and 89 years with the mean age of 61.4 ± 11.5 years. The mean body mass index (BMI) of this group was 26.3 ± 4.0 kg/m². The participants in this group were diagnosed with 54 posterior canals (78%), 9 multiple canals (14%), 5 lateral canals (7%), and 1 anterior canal (1%).The control group consisted of 17 males (25%) and 51 females (75%). Ages were between 36 and 80 years with the mean age of 60.0 ± 11.6 years. The mean BMI of this group was 25.3 ± 3.9 kg/m². There was no statistically significant difference in age, sex, or BMI between the 2 groups, as shown in Table 1.The mean serum vitamin D levels of the BPPV group were significantly lower than the control group (P value = .001), as shown in Table 2 (21.5 ± 5.3 ng/mL compared to 26.3 ± 6.8 ng/mL). However, there was no statistically significant difference between the first diagnosis of BPPV group and the recurrent BPPV group (P value = .313), as shown in Table 3 (21.0 ± 5.9 ng/mL compared to 21.9 ± 4.9 ng/mL). Moreover, the prevalence of vitamin D deficiency in patients with BPPV was higher than volunteers (44% compared to 19%, Figure 1).DiscussionOtoconia consists of CaCO3 or calcite crystal as the main component. The core of otoconia is composed of glycoprotein. Bones, teeth, and otoconia contain similar minerals.^21-23 The mechanism of calcium storage in otoconia is similar to bone. Calcium ions can be collected and released from otoconia according to the amount of calcium concentration in the vestibule of the inner ear.²⁴ The study of the structure of otoconia in animals, using immunogold techniques via electron microscopy, found that if the surface layer of the otoconia is demineralized, there would be a weakening of the fibrils interconnecting otoconia. As a result, detached otoconia may be easier released into the endolymphatic space.²⁵ The ability of calcium resorption as a component in the production of otoconia decreases with increasing age,²² which is consistent with the incidence of BPPV that is more common in people older than 60 years.²⁶ Previously, some animal studies have found that vitamin D regulates the expression of certain calcium-binding proteins through the vitamin D receptor at epithelial cells in the inner ear.²⁷ Furthermore, mice with vitamin D receptor-deficiency showed some balance problems.²⁸ Therefore, serum vitamin D levels and BPPV might be associated with each other.Tab2Tab3Jeong et al found that the prevalence of osteopenia and osteoporosis were higher in both women and men with BPPV than those in the controls.⁹ This finding was consistent with many studies that reported on the relationship of low bone mineral density and patients with BPPV.^4-9 So, it might be suggested that there is some abnormal calcium metabolism in patients with BPPV.Currently, studies on the relationship between low serum vitamin D levels and the occurrence of BPPV remain inconclusive. This study is to examine serum vitamin D levels in patients with BPPV compared to the controls. We found that (1) patients in the BPPV group had significantly lower serum vitamin D levels than those in the control group. (2) There was no difference in serum vitamin D levels between patients in the first diagnosis of BPPV group and the recurrent BPPV group. (3) The prevalence of vitamin D deficiency in the BPPV group was higher than that of the control group.Fig1This study consisted of women and men aged between 36 and 89 years. We found that the BPPV group had significantly lower serum vitamin D levels compared to the control group (21.5 ± 5.3 ng/mL compared to 26.3 ± 6.8 ng/mL, P value = .001). Furthermore, the prevalence of vitamin D deficiency in patients with BPPV was higher than the control group (44% compared to 19%) which was consistent with many previous studies.^8,10,14 Yang et al found the relationship between low serum vitamin D levels in men and the occurrence of BPPV,¹⁰ and Lee et al found that osteoporosis and vitamin D deficiency was linked to the occurrence of BPPV.⁸ Moreover, Han et al studied the vitamin D levels in postmenopausal women with BPPV and found that low serum vitamin D levels were associated with the occurrence of BPPV in postmenopausal women.¹⁴ Other studies have also concluded the same direction as the above.^12,13,29,30However, some studies have shown no relationship between BPPV and vitamin D deficiency.^17-19 They concluded that vitamin D deficiency in patients with BPPV is only a coincidence. Two of them were conducted in Turkey that had a higher prevalence of vitamin D deficiency than Thailand (74.9%³¹ compared to 5.7% to 31.8%^32,33). The mean serum vitamin D levels in Turkey is 16.9 ± 13.09 ng/mL³¹, whereas the mean vitamin D levels in Thailand is 27.1 ± 6.3 ng/mL³³ to 31.8 ± 8.5 ng/mL.³² In our study, the prevalence of vitamin D deficiency was 31.4%. This may result in different findings between studies.In the current study, there was no statistically significant difference in the levels of the serum vitamin D levels between the recurrent BPPV group and the first diagnosis of the BPPV group (21.9 ± 4.9 ng/mL compared to 21.0 ± 5.9 ng/mL). Serum vitamin D levels in both subgroups were lower than the control group. This finding was in accordance with the result of Jeong et al.¹³ Nonetheless, there are some controversies regarding the relationship of vitamin D levels between the first diagnosis of the BPPV group and the recurrent BPPV group. The study of Ding et al showed the serum vitamin D levels were lower in the recurrent BPPV group than in the first diagnosis of the BPPV group.³⁰Talaat et al¹⁶ studied the treatment of vitamin D deficiency in patients with BPPV combined with canalith repositioning procedure and monitored serum vitamin D levels for 18 months. As a result, they concluded that the recurrences might possibly be prevented with supplementary vitamin D, especially in those with recurrent idiopathic BPPV. In addition, Sheikhzaden et al¹⁵ divided patients with BPPV with vitamin D deficiency into 2 groups as follows: the treatment group and the control group. Both groups received canalith reposition therapy but the treatment group received an additional supplement of vitamin D to achieve a normal level. The findings of this study indicate that the normalization of serum vitamin D significantly reduces BPPV recurrences.This study may still have limitations in summarizing the relationship between low serum vitamin D levels and the occurrence of BPPV, due to the small number of studies. But according to data from this study, we found that low serum vitamin D levels were associated with the occurrence of BPPV, both in patients with the first diagnosis of BPPV group and the recurrent BPPV group. Therefore, the treatment of vitamin D deficiency may prevent the occurrence of BPPV or the recurrent BPPV. Further longitudinal studies with larger samples are warranted to evaluate the efficacy of vitamin D deficiency’s treatment for preventing the occurrence of BPPV or recurrent BPPV.ConclusionThis study revealed the relationship between low serum vitamin D levels and BPPV. This relationship was found in both patients with the recurrent BPPV and patients with the first diagnosis of BPPV. Therefore, low serum vitamin D levels may be one of the risk factors for BPPV. This research suggests that vitamin D normalization may be a therapeutic approach to BPPV, and further research should be performed to understand the effect of vitamin D supplements on the occurrence or the recurrence of BPPV.Authors’ NoteThis study was approved by Ethical Clearance Committee on Human Rights Related to Research Involving Human Subjects, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand.AcknowledgmentsThe authors thank Sukanya Siriyotha in the Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University for contributions to the statistical analysis performed in this manuscript.Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.FundingThe author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by ‘‘Research Funding from Faculty of Medicine, Ramathibodi Hospital, Mahidol University.’’ORCID iDKanokporn Sarsitthithum, MD

https://orcid.org/0000-0001-9843-2706
References

von Brevern M, Bertholon P, Brandt T, et al. Benign paroxysmal positional vertigo: diagnostic criteria consensus document of the Committee for the Classification of Vestibular Disorders of the Barany Society. Acta Otorrinolaringol Esp. 2017;68(6):349-360. doi:10.1016/j.otorri.2017.02.007

Lopez-Escamez JA, Gamiz MJ, Fernandez-Perez A, Gomez-Finana M, Sanchez-Canet I. Impact of treatment on healthrelated quality of life in patients with posterior canal benign paroxysmal positional vertigo. Otol Neurotol. 2003;24(4):637-641.

De Stefano A, Dispenza F, Suarez H, et al. A multicenter observational study on the role of comorbidities in the recurrent episodes of benign paroxysmal positional vertigo. Auris Nasus Larynx. 2014;41(1):31-36. doi:10.1016/j.anl.2013.07.007

Kim SY, Han SH, Kim YH, Park MH. Clinical features of recurrence and osteoporotic changes in benign paroxysmal positional vertigo. Auris Nasus Larynx. 2017;44(2):156-161 doi:10.1016/j.anl.2016.06.006

Parham K, Leonard G, Feinn RS, Lafreniere D, Kenny AM. Prospective clinical investigation of the relationship between idiopathic benign paroxysmal positional vertigo and bone turnover: a pilot study. Laryngoscope. 2013;123(11):2834-2839. doi:10.1002/lary.24162

Talaat HS, Abuhadied G, Talaat AS, Abdelaal MS. Low bone mineral density and vitamin D deficiency in patients with benign positional paroxysmal vertigo. Eur Arch Otorhinolaryngol. 2015; 272(9):2249-2253. doi:10.1007/s00405-014-3175-3

Yu S, Liu F, Cheng Z, Wang Q. Association between osteoporosis and benign paroxysmal positional vertigo: a systematic review. BMC Neurol. 2014;14:110. doi:10.1186/1471-2377-14-110

Lee SB, Lee CH, Kim YJ, Kim HM. Biochemical markers of bone turnover in benign paroxysmal positional vertigo. PLoS One. 2017;12(5):e0176011. doi:10.1371/journal.pone.0176011

Jeong SH, Choi SH, Kim JY, Koo JW, Kim HJ, Kim JS. Osteopenia and osteoporosis in idiopathic benign positional vertigo. Neurology. 2009;72(12):1069-1076. doi:10.1212/01.wnl.0000345016.33983.e0

Chan KC, Tsai YT, Yang YH, Chen PC, Chang PH. Osteoporosis is associated with increased risk for benign paroxysmal positional vertigo: a nationwide population-based study. Arch Osteoporos. 2017;12(1):106. doi:10.1007/s11657-017-0403-7

Yamanaka T, Shirota S, Sawai Y, Murai T, Fujita N, Hosoi H. Osteoporosis as a risk factor for the recurrence of benign paroxysmal positional vertigo. Laryngoscope. 2013;123(11): 2813-2816. doi:10.1002/lary.24099

Rhim GI. Serum vitamin D and recurrent benign paroxysmal positional vertigo. Laryngoscope Investig Otolaryngol. 2016; 1(6):150-153. doi:10.1002/lio2.35

Jeong SH, Kim JS, Shin JW, et al. Decreased serum vitamin D in idiopathic benign paroxysmal positional vertigo. J Neurol. 2013; 260(3):832-838. doi:10.1007/s00415-012-6712-2

Han W, Fan Z, Zhou M, et al. Low 25-hydroxyvitamin D levels in postmenopausal female patients with benign paroxysmal positional vertigo. Acta Otolaryngol. 2018;138(5):443-446. doi:10.1080/00016489.2017.1416168

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):173-177.

Talaat HS, Kabel AM, Khaliel LH, Abuhadied G, El-Naga HA, Talaat AS. Reduction of recurrence rate of benign paroxysmal positional vertigo by treatment of severe vitamin D deficiency. Auris Nasus Larynx. 2016;43(3):237-241. doi:10.1016/j.anl.2015.08.009

Karatas A, Acar Yuceant G, Yuce T, Haci C, Cebi IT, Salviz M. Association of benign paroxysmal positional vertigo with osteoporosis and vitamin D deficiency: a case controlled study. J Int Adv Otol. 2017;13(2):259-265. doi:10.5152/iao.2016.2640

Maslovara S, Butkovic Soldo S, Sestak A, Milinkovic K, Rogic-Namacinski J, Soldo A. 25 (OH) D3 levels, incidence and recurrence of different clinical forms of benig paroxysmal positional vertigo. Braz J Otorhinolaryngol. 2018;84(4):453-459. doi:10.1016/j.bjorl.2017.05.007

Cikrikci Isik G, Cevik Y, Emektar E, Corbacioglu S. Analysis of vitamin D and calcium levels in benign paroxysmal positional vertigo. Eurasian J Emerg Med. 2017;16(3):128-132.

Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96(7):1911-1930 doi:10.1210/jc.2011-0385

Ross MD, Pote KG, Rarey KE, Verma LM. Microdisc gel electrophoresis in sodium dodecyl sulfate of organic material from rat otoconial complexes. Ann N Y Acad Sci. 1981;374:808-819 doi: 10.1111/j.1749-6632.1981.tb30921.x

Johnsson LG, Rouse RC, Wright CG, Henry PJ, Hawkins JEJr. Pathology of neuroepithelial suprastructures of the human inner ear. Am J Otolaryngol. 1982;3(2):77-90.

Lins U, Farina M, Kurc M, et al. The otoconia of the guinea pig utricle: internal structure, surface exposure, and interactions with the filament matrix. J Struct Biol. 2000;131(1):67-78. doi:10.1006/jsbi.2000.4260

Hughes I, Thalmann I, Thalmann R, Ornitz D.Mixing model systems: using zebrafish and mouse inner ear mutants and other organ systems to unravel the mystery of otoconial development. Brain Res. 2006;1091(1):58-74. doi:10.1016/j.brainres.2006.01.074

Andrade LR, Lins U, Farina M, Kachar B, Thalmann R. Immunogold TEM of otoconin 90 and otolin—relevance to mineralization of otoconia, and pathogenesis of benign positional vertigo. Hear Res. 2012;292(1-2):14-25. doi:10.1016/j.heares.2012.07.003

von Brevern M, Radtke A, Lezius F, et al. Epidemiology of benign paroxysmal positional vertigo: a population based study. J Neurol Neurosurg Psychiatry. 2007;78(7):710-715. doi:10.1136/jnnp.2006.100420

Yamauchi D, Raveendran NN, Pondugula SR, et al. Vitamin D upregulates expression of ECaC1 mRNA in semicircular canal. Biochem Biophys Res Commun. 2005;331(4):1353-1357. doi:10.1016/j.bbrc.2005.04.053

Minasyan A, Keisala T, Zou J, et al. Vestibular dysfunction in vitamin D receptor mutant mice. J Steroid Biochem Mol Biol. 2009;114(3-5):161-166. doi:10.1016/j.jsbmb.2009.01.020

Wu Y, Gu C, Han W, Lu X, Chen C, Fan Z. Reduction of bone mineral density in native Chinese female idiopathic benign paroxysmal positional vertigo patients. Am J Otolaryngol. 2018; 39(1):31-33. doi:10.1016/j.amjoto.2017.09.004

Ding J, Liu L, Kong WK, Chen XB, Liu X. Serum levels of 25-hydroxy vitamin D correlate with idiopathic benign paroxysmal positional vertigo. Biosci Rep. 2019;39(4). doi:10.1042/bsr20190142

Hekimsoy Z, Dinc G, Kafesciler S, et al. Vitamin D status among adults in the Aegean region of Turkey. BMC Public Health. 2010; 10. doi:10.1186/1471-2458-10-782

Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B. Regional variation and determinants of vitamin D status in sunshineabundant Thailand. BMC Public Health. 2011;11:853 doi:10.1186/1471-2458-11-853

Chailurkit LO, Kruavit A, Rajatanavin R. Vitamin D status and bone health in healthy Thai elderly women. Nutrition. 2011;27(2): 160-164. doi:10.1016/j.nut.2009.12.001

¹ Department of Otolaryngology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand² Department of Otolaryngology, Queen Savang Vadhana Memorial Hospital, Chonburi, ThailandReceived: February 22, 2021; revised: February 22, 2021; accepted: March 18, 2021Corresponding Author:Tosapohn Wisupagan, MD, Department of Otolaryngology, Ramathibodi Hospital, 270 Rama VI road, Thung Phaya Thai, Ratchathewi, Bangkok 10400, Thailand.Email: twisupagan@gmail.comJournal CoverPeer ReviewersXlearEditorial Board 1EoseraEditorial Board 2VA Northeast OhioSAGE VideoVanderbilt University Medical CenterConnect with Sage JournalsIntraosseous Hemangioma of the Ethmoid SinusA “terrible” headache in a HIV patientBlastomyces induced otomastoiditis with local soft tissue invasion: A case reportCholesteatoma surgery with a dehiscent high jugular bulb treated with surgery assisted withLaryngeal obstruction due to Blue rubber bleb nevus syndromeFrontal angle: a new predictor of difficulty in endoscopic frontal sinus surgeryRole of bilateral inferior turbinoplasty as an adjunct to septoplasty in improvingOlfactory Cleft Opacification in COVID-19 Related Smell Loss: CTEffects of Supine and Prone Positions on Nasal Patency in Healthy IndividualsRelative humidity affects acute otitis media visits of preschoolThe Association between Serum Vitamin D Levels and Benign Paroxysmal Positional VertigoOnline Article Cover PagePresentation of External Ear Rosai-Dorfman Disease with Laryngeal InvolvementVersoMcKeon