Clinical Outcomes in Patients With Benign Paroxysmal Positional Vertigo and Vitamin D Deficiency: A Singaporean Perspective

Introduction: Benign paroxysmal positional vertigo (BPPV) is the primary vestibular disorder causing peripheral vertigo. Given the role of vitamin D in maintaining otoconia homeostasis, its deficiency may elevate the risk of BPPV. Our study seeks to evaluate the correlation between vitamin D deficiency and clinical outcomes of patients with BPPV in the local Asian population. Methodology: We performed a retrospective analysis of 149 consecutive adult patients referred to a tertiary center's Otolaryngology dizziness clinic between 2018 and 2021. All of these patients had both BPPV and vitamin D deficiency. Results: The mean serum vitamin D level was 19.4 ± 5.5 ng/mol. Approximately 51.7% (77/149) of patients experienced recurrent episodes of BPPV. Univariate Chi-square analyses demonstrated vitamin D levels (P < 0.001) and history of migraine (P = 0.04) were related to BPPV recurrence. On multivariate analyses, patients with higher serum vitamin D levels were 16.7% less likely to develop recurrent BPPV (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.76-0.90, P < 0.001). However, migraine history was not significantly related to BPPV recurrence (OR 0.38, 95% CI 0.14-1.00, P = 0.050). There was no statistically significant difference in the duration of BPPV episodes based on vitamin D levels (P = 0.327). Conclusions: Patients with vitamin D deficiency are at higher risk of recurrent BPPV. Future research directions that would be beneficial include conducting a randomized controlled trial to evaluate both the effectiveness of vitamin D supplementation and its optimal dosage.


Introduction
Benign paroxysmal positional vertigo (BPPV) affects up to 0.6% of the general population every year [1].It is the primary vestibular disorder causing peripheral vertigo, comprising up to 20% to 30% of cases [2,3].Individuals with BPPV typically report episodic positional vertigo, which lasts for a few seconds to several minutes.On positioning maneuvers, nystagmus is observed in the plane corresponding to the affected canal.The pathophysiology of BPPV involves canalolithiasis or cupulolithiasis, wherein displaced otoconia migrate from the macula to the semicircular canals [4,5].
In 80% of patients, BPPV is idiopathic.Risk factors in the remaining 20% include head trauma, vestibular neuronitis, and otologic surgery [6].Recent literature indicates a potential link between vitamin D deficiency and an elevated risk of developing BPPV; however, this is yet to be evaluated in the local Asian population [7].
Otoconia contain calcium carbonate on an organic collagen matrix (otolin).It is postulated that vitamin D is a key regulator of epithelial calcium channels and calcium-binding proteins, helping to maintain endolymphatic calcium levels.As a result of vitamin D deficiency, calcium metabolism is disrupted, leading to the development of abnormal otoconia.This, in turn, contributes to the onset of BPPV [8,9].Vitamin D deficiency is especially prevalent in Singapore, despite its equatorial location [10].Cross-sectional studies have reported vitamin D deficiency rates of up to 42% [11].The consequences of this deficiency include osteoporosis, muscle pain, and weakness.
Our retrospective cohort study seeks to evaluate the correlation between vitamin D deficiency and clinical outcomes of patients with BPPV in the local Asian population.

Study design and participants
This retrospective cohort study was carried out at a tertiary referral center.Approval from the SingHealth Institutional Review Board (IRB) was obtained for waiver of informed consent (IRB reference number 2021/2376).All data retrospectively collected from the medical records were de-identified to ensure anonymity.

Inclusion criteria
We identified 149 consecutive adult patients (21 years old and above), who were referred to Singapore General Hospital's Otolaryngology dizziness clinic, between 2018 and 2021.All of the patients in this retrospective cohort study had both BPPV and vitamin D deficiency.
On initial presentation to the dizziness clinic, patients were diagnosed with BPPV if they had a classical history (positional vertigo related to head movements, lasting seconds to minutes), positive clinical examination findings (positional nystagmus with Dix-Hallpike or supine roll maneuvers, with latency and fatiguability), or both.
A history of previous BPPV was determined based on clinical documentation review, if the patient had a prior documented episode of BPPV diagnosed by an otolaryngologist, or a classical history with complete resolution of symptoms in between the previous episode and the current one for which they presented.
The diagnosis of migraine was established through a clinical documentation review, which involved confirming that the patient had either a documented medical history of migraine or, in cases where they had not previously sought treatment, had reported symptoms consistent with the diagnostic criteria for migraine with or without aura as outlined by the International Headache Society.These criteria include experiencing at least five headaches along with at least two of the following features: unilateral pain, pulsating quality, at least moderate intensity, exacerbation with routine activities, with either nausea/vomiting and/or photophobia and phonophobia.
Serum vitamin D levels were measured at initial clinical presentation, and levels below 30 ng/mL were considered deficient.

Exclusion criteria
Patients with a history of head or ear trauma, surgery, or a history of active inner ear disease were excluded.Those who had incomplete data were excluded as well.

Statistical analysis
Variables were summarized using descriptive statistics.Tests of normality for each scale variable were performed using the Shapiro-Wilk test.The effect of various factors on BPPV recurrence was evaluated using binomial logistic regression through odds ratios (ORs) and 95% confidence interval (CI).The suitability of the model was assessed using the Hosmer-Lemeshow goodness-of-fit test.To determine statistical significance, an alpha level of 0.05 was established.IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY) was used for analyses.

Factors affecting BPPV recurrence
The factors affecting BPPV recurrence are shown in  Subsequent multivariate binomial logistic regression showed patients with higher serum vitamin D levels are 16.7% less likely to develop recurrent BPPV (OR 0.83, 95% CI 0.76-0.90,P < 0.001).However, this analysis showed no significant association between migraine and BPPV recurrence (OR 0.83, 95% CI 0.76-0.90,P = 0.050).

Effect of vitamin D deficiency on the duration of BPPV episodes
The characteristics of BPPV episodes are shown in Table 3.A Kruskall Wallis test showed no significant association between the duration of BPPV episodes and serum vitamin D levels (H = 6.88,P = 0.327).

Factors affecting serum vitamin D levels
The factors affecting serum vitamin D levels are presented in

Discussion
Our study demonstrated patients with vitamin D deficiency are more likely to experience BPPV recurrence.There was, however, no direct association between serum vitamin D levels (0-30 ng/mol) and duration of BPPV exacerbations.
In countries that experience seasonal variations, vitamin D deficiency is prevalent, especially in winter months [12].Surprisingly, even in tropical Singapore, there is a significant prevalence of vitamin D deficiency.This may be related to working long hours in indoor environments.Even among those whose offices have windows, the glass filters out UVB.As such, exposure to indoor sunlight does not result in vitamin D production [13].Moreover, a fair complexion tends to be viewed as desirable in East Asian societies [14].There is thus an increased propensity to engage in sun avoidance measures, such as hatwearing, utilization of long-sleeved clothing, and application of sunscreen [15].
Our study identified a correlation between lower vitamin D levels and younger age.Possible underlying factors include increased time spent indoors during daytime hours, leading to less exposure to sunlight and UVB absorption [13].Older adults on follow-up with primary care services for comorbidities such as osteoporosis are started on vitamin D supplementation [16].Generally, the prevalence of BPPV rises as individuals age.However, in younger individuals, the occurrence of recurrent BPPV is uncommon, and low vitamin D levels might be a contributory factor.
Because of the link between vitamin D deficiency and recurrent BPPV, there is potential to increase vitamin D levels to reduce the risk of recurrent BPPV.Vitamin D can be derived from environmental sources such as sunlight exposure; however, it is fraught with challenges.Prolonged exposure may result in DNA damage and cutaneous malignancies; thus, exposure should be limited to low levels [17].Equatorial nations like Singapore are subjected to intense sunlight at midday.While less intense, the morning sun contains UVA, which can cause skin reddening without vitamin D synthesis.In the context of Southeast Asia, in order to sustain adequate vitamin D levels, Nimitphong and Holick suggested a regimen of exposing the face and both arms to sunlight for 25 minutes, three times a week, starting at 9 AM [15].Additionally, for the vitamin D deficient, there is potential for vitamin D supplementation to augment dietary sources.Future research directions that would be beneficial include conducting a randomized controlled trial to evaluate both the effectiveness of vitamin D supplementation and its optimal dosage.
The role of migraine as a risk factor for recurrent BPPV is uncertain.Zhu et al. demonstrated patients with migraine had an increased risk of developing recurrent BPPV; however, Hilton et al. showed there was no relationship [18,19].It is postulated that migraine may result in labyrinthine artery vasospam and ischemia, causing oxidative stress and otoconia detachment from otolith organs [20].Our study showed no significant association; however, the proportion of patients in our study population with migraine was low (n = 33, 22.1%).Further studies would need to be carried out to assess this relationship in our local Singaporean context.
A meta-analysis by Chen et al. in 2021 suggested that in addition to vitamin D deficiency, patients with hypertension, hyperlipidemia, and diabetes mellitus were more likely to develop recurrent BPPV [21].However, our study did not demonstrate such a relationship.Of note, there was significant heterogeneity among the included studies.It would be beneficial to assess this correlation in larger scale cohorts.
It is interesting to note that the incidence of anterior canal BPPV in our study was 6.6%, higher than the frequency in literature of 1% to 3% [22].The incidence of lateral canal BPPV in our center was also higher at 22.4%, compared to most reports of 10% to 12% [23].
The strength of this study is uniform documentation of patient records in a single dizziness clinic.To the best of our knowledge, our study is the first to explore the relationship between vitamin D deficiency and BPPV in the local Singaporean and South East Asian context.Given the incidence of vitamin D deficiency and dizziness, this is an important springboard for further clinical trials.
Limitations of this study include retrospective data collection from our cohort.Additionally, all patients had their serum vitamin D levels assessed on first presentation to the otolaryngology dizziness clinic, but not all had a repeat serum vitamin D level tested.As such, our analysis only utilized the first vitamin D reading.

Conclusions
In conclusion, BPPV and vitamin D deficiency are especially prevalent in Singapore, causing economic burden and loss of quality of life.This is the first study on vitamin D deficiency and BPPV in the local Singaporean and South East Asian context.Our analysis demonstrated patients with vitamin D deficiency are at higher risk of recurrent BPPV.These findings serve as a springboard for future clinical trials, which include evaluating both the effectiveness of vitamin D supplementation and its optimal dosage.not involve animal subjects or tissue.Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work.Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

FIGURE 3 :
FIGURE 3: Frequency distribution of patients' total symptom duration.