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Relationship of vitamin D levels with clinical presentation and recurrence of BPPV in a Southeastern United States institution

      ABSTRACT

      Objective

      To examine the relationship of 25hydroxyvitamin D serum levels with BPPV incidence and recurrence rates.

      Methods

      A retrospective cross-sectional, case-controlled study with follow-up phone survey was performed on patients diagnosed with BPPV between 05/2017-05/2020, who had available 25hydroxyvitamin D serology. Patients were seen at a multidisciplinary, vestibular-focused, neurotology clinic at a tertiary referral center. Controls consisted of subjects from the National Health and Nutrition Examination Survey (NHANES), and a locoregional age, sex, and race-matched group of patients from our institution.

      Results

      Our BPPV cohort consisted of 173 patients (mean age 66.2 ± 11.8 years), who were predominately female (75.7%) and Caucasian (76.3%). Almost all age subgroups (BPPV, NHANES, and locoregional groups) ≤60 years old had insufficient levels of vitamin D. However, the overall BPPV cohort had a significantly higher vitamin D level than the NHANES control (31.4 ± 16.5 v. 26.0 ± 11.2 ng/mL, d=0.474 [0.323, 0.626]). There was no significant difference when compared to the overall locoregional control (31.4 ± 20.5 ng/mL). Migraines were significantly correlated to increased BPPV recurrence rates on univariate (beta=0.927, p=0.037, 95% CI: [0.057, 1.798]) and multiple regression analyses (beta=0.231, 95% CI: [0.024, 2.029], p=0.045). Furthermore, patients with BPPV recurrences had significantly lower levels of vitamin D at initial presentation when compared to patients with no recurrences (29.0 ± 12.0 v. 37.6 ± 18.3 ng/mL, d=0.571[0.139,1.001]).

      Conclusion

      Many BPPV patients in our cohort had insufficient vitamin D levels, and patients with BPPV recurrences had insufficient and significantly lower vitamin D levels than those without. As a readily available and affordable supplement, vitamin D may be used as an adjunct treatment but prospective studies should be done to confirm if it can prevent or reduce recurrence.

      Keywords

      Abbreviations:

      BPPV (Benign paroxysmal positional vertigo)

      1. Introduction

      An estimated one-third of Americans will have vertigo throughout their lifetime.[
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      Vestibular dysfunction: prevalence, impact and need for targeted treatment.
      ] The most common cause of this pathology is benign paroxysmal positional vertigo (BPPV), accounting for 10-27% of vertigo diagnoses.[
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      Vestibular dysfunction: prevalence, impact and need for targeted treatment.
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      ] BPPV is known for high recurrence rates, ranging from 27-37% in recent population studies.[
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      ]
      It is accepted that BPPV is caused by otoconia, or calcium carbonate crystals, that dislodge into the semicircular ducts, causing vertigo and nystagmus with changes in head position. However, the pathophysiology of this disease is unknown. BPPV has known risk factors of older age (>60), sex (female>male), osteoporosis, migraine, hypertension, hyperlipidemia, and smoking.[
      • Tirelli G
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      Repeated canalith repositioning procedure in BPPV: effects on recurrence and dizziness prevention.
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      • Oron Y
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      Treatment of horizontal canal BPPV: pathophysiology, available maneuvers, and recommended treatment.
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      • Babac S
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      Why do treatment failure and recurrences of benign paroxysmal positional vertigo occur?.
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      • Zhu CT
      • Zhao XQ
      • Ju Y
      • Wang Y
      • Chen MM
      • Cui Y.
      Clinical characteristics and risk factors for the recurrence of benign paroxysmal positional vertigo.
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      • Feldmann M
      • Ziese T
      • Lempert T
      • et al.
      Epidemiology of benign paroxysmal positional vertigo: a population based study.
      ] Furthermore, vertigo as a symptom of BPPV can increase the risk of falls 12-fold, implicating BPPV as a “gateway” for trauma-related injuries.[
      • Agrawal Y
      • Ward BK
      • Minor LB.
      Vestibular dysfunction: prevalence, impact and need for targeted treatment.
      ]
      Despite the burden of BPPV on patients’ medical and social well-being, it is considered a benign disorder. The American Academy of Otolaryngology-Head and Neck Surgery guidelines currently recommend canalith repositioning exercises, such as the Epley maneuver, or habituation exercises, such as the Brandt-Daroff exercises, as primary treatments for BPPV.[
      • Tirelli G
      • Nicastro L
      • Gatto A
      • Tofanelli M.
      Repeated canalith repositioning procedure in BPPV: effects on recurrence and dizziness prevention.
      ,
      • Oron Y
      • Cohen-Atsmoni S
      • Len A
      • Roth Y
      Treatment of horizontal canal BPPV: pathophysiology, available maneuvers, and recommended treatment.
      ,
      • Pereira AB
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      • Volpe FM.
      Effect of Epley's maneuver on the quality of life of paroxismal positional benign vertigo patients.
      ,
      • Epley JM.
      The canalith repositioning procedure: for treatment of benign paroxysmal positional vertigo.
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      • Bhattacharyya N
      • Baugh RF
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      • Cass S
      • et al.
      Clinical practice guideline: benign paroxysmal positional vertigo.
      ,
      • Azad T
      • Pan G
      • Verma R.
      Epley maneuver (Canalith Repositioning) for benign positional vertigo.
      ] While effective at resolving BPPV episodes, physical therapy does not significantly reduce BPPV recurrence rates and it is unclear why some patients are more prone to recurrences than others.[
      • Tirelli G
      • Nicastro L
      • Gatto A
      • Tofanelli M.
      Repeated canalith repositioning procedure in BPPV: effects on recurrence and dizziness prevention.
      ,
      • Oron Y
      • Cohen-Atsmoni S
      • Len A
      • Roth Y
      Treatment of horizontal canal BPPV: pathophysiology, available maneuvers, and recommended treatment.
      ]
      As otoconia are composed of calcium carbonate crystals, and vitamin D is responsible for calcium and phosphate homeostasis, vitamin D is speculated to have a role in the pathophysiology of BPPV.[
      • Oron Y
      • Cohen-Atsmoni S
      • Len A
      • Roth Y
      Treatment of horizontal canal BPPV: pathophysiology, available maneuvers, and recommended treatment.
      ,
      • Byun H
      • Chung JH
      • Lee SH
      • Park CW
      • Kim EM
      • Kim I.
      Increased risk of benign paroxysmal positional vertigo in osteoporosis: a nationwide population-based cohort study.
      ,
      • Büki B
      • Ecker M
      • Jünger H
      • Lundberg YW.
      Vitamin D deficiency and benign paroxysmal positioning vertigo.
      ,
      • Agrawal Y
      • Carey JP
      • Della Santina CC
      • Schubert MC
      • Minor LB
      Disorders of balance and vestibular function in US adults: data from the national health and nutrition examination survey, 2001-2004.
      ] Significant correlations between osteoporosis, represented by biomarkers of bone turnover, and BPPV occurrence have been reported.[
      • Babac S
      • Djeric D
      • Petrovic-Lazic M
      • Arsovic N
      • Mikic A.
      Why do treatment failure and recurrences of benign paroxysmal positional vertigo occur?.
      ,
      • Zhu CT
      • Zhao XQ
      • Ju Y
      • Wang Y
      • Chen MM
      • Cui Y.
      Clinical characteristics and risk factors for the recurrence of benign paroxysmal positional vertigo.
      ,
      • Sacks D
      • Parham K.
      Preliminary report on the investigation of the association between BPPV and osteoporosis using biomarkers.
      ,
      • Bruintjes TD
      • van der Zaag-Loonen HJ
      • Eggelmeijer F
      • van Leeuwen RB.
      The prevalence of benign paroxysmal positional vertigo in patients with osteoporosis.
      ] A study by Byun et. al. found osteoporosis patients were at a 1.75 times higher risk of BPPV development.[
      • Byun H
      • Chung JH
      • Lee SH
      • Park CW
      • Kim EM
      • Kim I.
      Increased risk of benign paroxysmal positional vertigo in osteoporosis: a nationwide population-based cohort study.
      ] As a result, vitamin D supplementation has been proposed as a preventive treatment of recurrences.[
      • Büki B
      • Ecker M
      • Jünger H
      • Lundberg YW.
      Vitamin D deficiency and benign paroxysmal positioning vertigo.
      ,
      • Il Rhim G
      Serum vitamin D and recurrent benign paroxysmal positional vertigo.
      ,
      • Jeong S-H
      • Lee S-U
      • Kim J-S.
      Prevention of recurrent benign paroxysmal positional vertigo with vitamin D supplementation: a meta-analysis.
      ] However, current literature is divided regarding the significance of vitamin D levels of patients with BPPV.[
      • Büki B
      • Ecker M
      • Jünger H
      • Lundberg YW.
      Vitamin D deficiency and benign paroxysmal positioning vertigo.
      ,
      • Meghji S
      • Murphy D
      • Nunney I
      • Phillips JS.
      The seasonal variation of benign paroxysmal positional vertigo.
      ,
      • Kahraman SS
      • Ozcan O
      • Arli C
      • Ustun I
      • Erduran R
      • Akoglu E
      • et al.
      Calcium homeostasis during attack and remission in patients with idiopathic benign paroxysmal positional vertigo.
      ,
      • Jeong SH
      • Kim JS
      • Shin JW
      • Kim S
      • Lee H
      • Lee AY
      • et al.
      Decreased serum vitamin D in idiopathic benign paroxysmal positional vertigo.
      ,
      • Talaat HS
      • Abuhadied G
      • Talaat AS
      • Abdelaal MSS.
      Low bone mineral density and vitamin D deficiency in patients with benign positional paroxysmal vertigo.
      ,
      • Talaat HS
      • Kabel AMH
      • Khaliel LH
      • Abuhadied G
      • El-Naga HAERA
      • Talaat AS.
      Reduction of recurrence rate of benign paroxysmal positional vertigo by treatment of severe vitamin D deficiency.
      ,
      • 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.
      ,
      • 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.
      ]
      In this cross-sectional study, we explored incidence of vitamin D deficiency in a single institution cohort. Two control groups were used for assessment of patient demographics and regional influences on vitamin D levels: 1) the National Health and Nutrition Examination Survey (NHANES), representative of the general United States adult population, and 2) an age, gender, and race-matched locoregional cohort from our institution.

      2. Materials and methods

      This study was approved by our Institutional Review Board (Protocol #95413). First, a retrospective cross-sectional analysis was performed by collecting data from the medical records of patients diagnosed with BPPV in our multidisciplinary, vestibular-focused, neurotology clinic between 5/2017 and 5/2020. Patients were seen by a neurotologist and a vestibular therapist, who verified resolution of BPPV in follow-up visits.
      Inclusion criteria for this study were: (i) upbeat torsional nystagmus on Dix-Hallpike maneuver (consistent with posterior canal BPPV), or horizontal geotropic/ apogeotropic nystagmus in the supine roll test for horizontal canalithiasis or cupulolithiasis (ii) 25hydroxyvitamin D serology result within six months of BPPV diagnosis, and (iii) ≥18 years of age. Patients with medical conditions affecting the ear or temporal bone (e.g. chronic otitis media) or comorbid conditions causing dizziness (e.g. Meniere's disease, especially since Meniere's disease is in itself a risk factor for BPPV) were excluded.[
      • Kutlubaev MA
      • Xu Y
      • Hornibrook J.
      Benign paroxysmal positional vertigo in Meniere's disease: systematic review and meta-analysis of frequency and clinical characteristics.
      ] We excluded patients with vestibular migraine but not those with migraine headaches. Patient charts were reviewed for vitamin D supplementation prior to BPPV diagnosis. A patient flowchart is presented in Fig. 1.
      Data relating to BPPV was extracted from medical records extra including: demographics, comorbid conditions, vitamin D levels, and BPPV recurrence. In clinical practice as well as in this paper, we used the Holick et al. definition of vitamin D sufficiency (>30 ng/mL), insufficiency (21-29 ng/mL), and deficiency (<21 ng/mL).[
      • Holick MF
      • Binkley NC
      • Bischoff-Ferrari HA
      • Gordon CM
      • Hanley DA
      • Heaney RP
      • et al.
      Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline.
      ]These are the latest guidelines from the Endocrine Society and are recommended by the American Geriatric Association.[
      Recommendations abstracted from the American Geriatrics Society Consensus statement on vitamin D for prevention of falls and their consequences.
      ]
      Second, patients were telephoned (3.02-52.21 months following their initial visit for BPPV) to determine: (i) additional episodes of BPPV, (ii) duration of episodes, (iii) severity of episodes, (iv) length of the series of episodes, (v) vitamin D dosage, and (vi) duration of vitamin D supplementation. Of note, criteria for BPPV recurrence included: (i) episodes lasting <60 seconds, (ii) consistency with previously observed induced episodes in-office, (iii) episodes induced by specific positions of the head, (iv) no other neurological signs (i.e. cerebellar/oculomotor signs) and (v) no other pertinent medical conditions attributable to the episode of vertigo (Fig. 3). Three attempts were made by phone call to reach patients. Of the n=173 patients included in this study, 108 patients were successfully contacted. Patients were occasionally unable or unwilling to answer questions within the phone survey, resulting in an individual “n” per question different than the n=108 total patients. For example, only 95 were successfully contacted for confirmation of vitamin D supplementation taken prior to diagnosis.
      To accurately analyze the influence of regional factors on the local patient cohort's 25hydroxyvitamin D levels, two control groups were utilized. The NHANES database served as the first control group, a comprehensive dataset of health and nutritional information collected and produced by the CDC. The aim of this dataset is to be representative of the general United States adult population (available at: https://www.cdc.gov/nchs/nhanes/index.htm). Of note, 25hydroxyvitamin D levels from our institution are reported in ng/mL. Thus, vitamin D levels from the NHANES database were converted from nmol/L to ng/mL using a conversion factor of 1 ng/mL=2.5 nmol/L.[
      • Yetley EA
      • Pfeiffer CM
      • Schleicher RL
      • Phinney KW
      • Lacher DA
      • Christakos S
      • et al.
      NHANES monitoring of serum 25-hydroxyvitamin D: A roundtable summary.
      ]The second control group was an age, sex, and race-matched locoregional cohort, curated by an institutional honest data broker (one of the BPPV patients was 91 years old and was not matched and later excluded from analysis when comparing the cohort to the locoregional control). These patients were treated at our institution, had a vitamin D serology in our system, were not on any vitamin D supplementation, and did not have any diagnoses pertaining to BPPV, dizziness or vitamin D deficiency, and were never seen for a main complaint of dizziness. For patients in the locoregional control group with vitamin D serology reported as <3.0 ng/mL, we used 0 ng/mL for statistical analyses.
      All data analyses were performed using SPSS® or Excel® (2013) software. For descriptive analysis of demographics, mean and standard deviations were determined. For comparison of vitamin D levels among subgroups, effect sizes were calculated using Cohen's d. Univariate and multiple regression analyses were utilized to identify potential risk factors for BPPV recurrence. Results were considered significant at p<0.05.

      3. Results

      3.1 Patient characteristics

      Of 680 BPPV patients seen in our clinic 05/2017-05/2020, 173 met inclusion criteria. A flowchart of patient selection is presented in Fig. 1. One hundred and sixty-nine patients (97.7%) had posterior canal BPPV, and 21 (12.1%) were diagnosed with bilateral BPPV. The most common comorbidities in the BPPV group were hyperlipidemia (n=67, 38.7%), hypertension (n=41, 23.7%), thyroid disease (n=33, 19.1%), asthma/allergic rhinitis (n=25, 14.5%), and diabetes mellitus (n=21, 12.1 %). Only 9.2% (n=16) of our patients had migraines despite a 13.5-15.3% prevalence of migraines in the general population in the US.[
      • Burch R
      • Rizzoli P
      • Loder E.
      The prevalence and impact of migraine and severe headache in the United States: figures and trends from government health studies.
      ,
      • Lipton RB
      • Stewart WF
      • Diamond S
      • Diamond ML
      • Reed M.
      Prevalence and burden of migraine in the United States: Data from the American Migraine Study II.
      ] The mean age of this cohort was 66.2 ± 11.8 years (Fig. 2) and 75.7% (n=131) were women. The cohort was 76.3% (n=132) Caucasian and 16.8% (n=29) African American (Table 1).
      Fig 2:
      Fig. 2Age Distribution of Patient Population
      Table 1Patient Demographics.
      BPPV cohort (n=173)NHANES (n=5962)d [95% CI]
      Mean (SD), or n%Mean (SD), or n%
      Age66.2 (11.8)46.7 (11.2)1.738 [1.584, 1.892]
      Male sex4224.3284547.70.471 [0.320, 0.622]
      Race
      White13276.3253542.50.671 [0.519, 0.823]
      Black2916.8118419.9
      Hispanic31.7137123.0
      Unknown/Other95.287214.6
      BPPV Type
      Unilateral152
      Bilateral21
      Posterior canal169
      Vitamin D supplementation (of n=95 patients with data)
      Took supplementation prior to diagnosis31
      <1000 IU13
      1001-5000 IU14
      >5000 IU4
      The NHANES control group (n=5962) had a mean age of 46.7 ± 11.62 years; 42.5% (n=2535) were Caucasian and 19.9% (n=1184) were African American. Compared to the NHANES group, the BPPV group was significantly older (66.2 ± 12.3 vs. 46.7 ± 11.2 years, d=1.738 [1.584,1.892]), had a lower proportion of males (24.3% vs. 47.7%, d=0.471 [0.320, 0.622]), and had a higher proportion of Caucasian patients than African-American patients (see Table 1,Fig. 1).

      3.2.1 Vitamin D subgroup analysis: NHANES control

      The BPPV group had a significantly higher mean vitamin D level at the time of BPPV diagnosis compared to the NHANES population (31.4 ± 16.5 vs. 26.0 ± 11.2 ng/mL, d=0.474 [0.323, 0.626]). Vitamin D level subgroup analyses by gender, age, and race are summarized in Table 2. Male, female, and Caucasian patients with BPPV had greater vitamin D levels than those of the NHANES population. Age subgroups did not reveal any significant differences, but both BPPV and NHANES patients between 30-40, 40-50, and 50-60 years of age had vitamin D levels below the upper range of normal (30 ng/mL).
      Table 2Vitamin D Levels in Subgroup Analyses. Comparison of 25hydroxyvitamin D levels between BPPV cohort and NHANES population subgroups.
      nSerum 25(OH)D (ng/mL)(mean, SD)d [95% CI]
      TotalBPPV

      NHANES
      173

      5962
      31.4 (16.5)

      26.0 (11.2)
      0.474 [0.323, 0.626]
      MaleBPPV

      NHANES
      42

      2845
      29.7 (12.9)

      24.9 (9.9)
      0.480 [0.329,0.632]
      FemaleBPPV

      NHANES
      131

      3117
      32.0 (17.5)

      27.1 (12.3)
      0.231 [0.056, 0.406]
      30-40BPPV

      NHANES
      5

      1057
      21.7 (4.5)

      23.5 (9.7)
      -0.186 [-1.065, 0.693]
      41-50BPPV

      NHANES
      11

      989
      24.5 (7.9)

      25.0 (10.0)
      -0.050 [-0.644, 0.544]
      51-60BPPV

      NHANES
      36

      909
      27.7 (17.3)

      26.6 (11.4)
      0.094 [-0.239, 0.427]
      61-70BPPV

      NHANES
      50

      860
      30.2 (18.1)

      28.5 (12.1)
      0.136 [-0.149, 0.421]
      71-80BPPV

      NHANES
      53

      786
      35.1 (14.9)

      32.9 (12.9)
      0.169 [-0.110, 0.447]
      Male ≤50BPPV

      NHANES
      1

      1631
      n/a

      23.2 (8.7)
      n/a
      Male 51-60BPPV

      NHANES
      10

      437
      22.1 (7.5)

      25.4 (10.3)
      -0.322 [-0.949, 0.305]
      Male 61-70BPPV

      NHANES
      8

      406
      24.2 (8.0)

      26.2 (9.8)
      -0.205 [-0.905, 0.495]
      Male 71-80BPPV

      NHANES
      16

      371
      34.0 (11.2)

      30.7 (11.7)
      0.283 [-0.218, 0.783]
      Female 30-40BPPV

      NHANES
      4

      552
      20.3 (3.5)

      23.8 (10.4)
      -0.377 [-1.321, 0.646]
      Female 41-50BPPV

      NHANES
      11

      531
      24.5 (7.9)

      25.5 (11.0)
      -0.091 [-0.688, 0.506]
      Female 51-60BPPV

      NHANES
      26

      471
      29.9 (19.5)

      27.7 (12.3)
      0.172 [-0.222, 0.567]
      Female 61-70BPPV

      NHANES
      42

      453
      31.3 (19.3)

      30.5 (13.5)
      0.057 [-0.259, 0.373]
      Female 71-80BPPV

      NHANES
      37

      414
      36.1 (16.5)

      34.8 (13.7)
      0.093 [-0.243, 0.430]
      CaucasianBPPV

      NHANES
      132

      2535
      33.3 (16.5)

      30.0 (11.4)
      0.282 [0.107, 0.457]
      African AmericanBPPV

      NHANES
      29

      1184
      24.6 (16.0)

      20.8 (11.0)
      -0.341 [-0.028,0.710]

      3.2.2 Vitamin D subgroup analysis: Locoregional control

      The locoregional control patients had similar vitamin D levels to that of BPPV patients overall (Table 3). However, males between 51-60 years of age with BPPV had a significantly lower vitamin D level than the locoregional control (22.1 ± 7.5 vs 33.9 ± 13.4 ng/mL). Furthermore, African-American males with BPPV had the lowest mean vitamin D levels of all subgroups (13.5 ± 1.6 ng/mL) which was significantly lower than that of the locoregional control (31.5 ± 2.3 ng/mL, d=8.950 [2.446, 15.454]).
      Table 3Vitamin D Level Analysis of BPPV Cohort and Locoregional Control Subgroups.
      nSerum 25(OH)D (ng/mL)(mean, SD)d [95% CI]
      Total
      NHANES and locoregional overall cohort numbers are not equivalent (n=173 v. 172) because we did not match the 91-year-old from the BPPV cohort, and this subject was not included in subsequent analyses.
      BPPV

      Locoregional
      17231.5 (16.5)

      32.4 (19.0)
      0.051 [-0.161, 0.262]
      MaleBPPV

      Locoregional
      4229.9 (13.0)

      31.3 (18.3)
      0.088 [-0.345, 0.521]
      FemaleBPPV

      Locoregional
      13132.0 (17.4)

      32.8 (19.2)
      0.044 [-0.199, 0.286]
      30-40BPPV

      Locoregional
      521.7 (4.4)

      22.6 (18.1)
      0.068 [-1.172, 1.308]
      41-50BPPV

      Locoregional
      1124.5 (7.9)

      32.9 (12.4)
      0.808 [-0.061, 1.677
      51-60BPPV

      Locoregional
      3627.7 (17.3)

      29.6 (13.7)
      0.122 [-0.341, 0.584]
      61-70BPPV

      Locoregional
      5030.2 (18.1)

      34.6 (19.4)
      0.235 [-0.159, 0.628]
      71-80BPPV

      Locoregional
      5335.1 (14.9)

      32.5 (22.1)
      0.138 [-0.243, 0.519]
      81-90BPPV

      Locoregional
      1739.7 (16.4)

      34.5 (21.0)
      0.276 [-0.400, 0.952]
      Male 30-40BPPV

      Locoregional
      1n/an/a
      Male 41-50BPPV

      Locoregional
      0n/an/a
      Male 51-60BPPV

      Locoregional
      1022.1 (7.5)

      33.9 (13.4)
      1.087 [0.148, 2.026]
      Male 61-70BPPV

      Locoregional
      824.2 (8.0)

      28.8 (15.2)
      0.378 [-0.610, 1.368]
      Male 71-80BPPV

      Locoregional
      1634.0 (11.2)

      33.1 (18.8)
      0.184 [-0.507, 0.882]
      Male 81-90BPPV

      Locoregional
      640.0 (20.6)

      28. 2 (29.4)
      0.465 [-0.682, 1.611
      Female 30-40BPPV

      Locoregional
      420.3 (3.5)

      24.7 (20.1)
      0.277 [-1.115, 1.670]
      Female 41-50BPPV

      Locoregional
      1124.5 (7.9)

      32.9 (12.4)
      0.808 [-0.061, 1.168]
      Female 51-60BPPV

      Locoregional
      2629.9 (19.5)

      28.0 (13.7)
      0.113 [-0.431, 0.657]
      Female 61-70BPPV

      Locoregional
      4231.3 (19.3)

      35.7 (20.1)
      0.223 [-0.206, 0.652]
      Female 71-80BPPV

      Locoregional
      3735.5 (16.4)

      32.2 (23.6)
      0.162 [-0.294, 0.619]
      Female 81-90BPPV

      Locoregional
      1139.5 (14.8)

      38.0 (15.3)
      0.100 [-0.737, 0.936]
      CaucasianBPPV

      Locoregional
      13234.8 (18.1)

      33.3 (19.4)
      0.080 [-0.223, 0.383]
      African AmericanBPPV

      Locoregional
      2918.9 (8.5)

      16.6 (8.6)
      0.269 [-0.475, 1.013]
      Caucasian maleBPPV

      Locoregional
      3731.8 (12.3)

      30.8 (16.7)
      0.068 [-0.388, 0.524]
      Caucasian femaleBPPV

      Locoregional
      9533.7 (17.6)

      34.1 (20.9)
      0.021 [-0.258, 0.299]
      African American maleBPPV

      Locoregional
      213.5 (1.6)

      31.5 (2.30)
      8.950 [2.446, 15.454]
      African American femaleBPPV

      Locoregional
      2725.5 (16.3)

      18.2 (11.5)
      0.518 [-0.025, 1.060]
      low asterisk NHANES and locoregional overall cohort numbers are not equivalent (n=173 v. 172) because we did not match the 91-year-old from the BPPV cohort, and this subject was not included in subsequent analyses.

      3.3 Vitamin D supplementation

      Of 95 patients with available data, 32.6% (n=31) took vitamin D supplementation prior to BPPV diagnosis. Of these patients, 31 were able to confirm their vitamin D dose taken prior to BPPV diagnosis: 41.9% (n=13) <1000 IU, 45.2% (n=14) 1001-5000 IU, and 12.9% (n=4) >5000 IU. Of 110 patients who took vitamin D supplementation following their BPPV diagnosis (collected by phone calls (n=108) and chart review (n=2)) 70 (63.6%) had been on vitamin D for >1 year, 19 (17.3%) had been on vitamin D for <1 year, and 21 (19.1%) were no longer on vitamin D supplementation.

      3.4 BPPV recurrence

      Follow-up telephone calls made a mean of 17.3 ± 15.6 months after initial BPPV diagnosis revealed a mean recurrence rate of 1 ± 2.75 episodes every 2.5 months, with a mean severity of 5 ± 2.7 out of 10 (a subjective measure similar to a visual analog scale, with patients instructed to select 10 as the most severe) per episode. The majority of patients attended vestibular physical therapy after being referred during their initial BPPV diagnosis (69.5%, n=121) (Table 4), which we recommend routinely. Notably, patients with no recurrences had significantly different (p=0.012) vitamin D levels compared to individuals with ≥1 recurrence (38.0 vs 29.4 ng/mL). However, there was no difference in recurrence rates between those who were on vitamin D supplementation compared to those who were not.
      Table 4Univariate Analyses of Comorbid Conditions of BPPV. The use of univariate analysis on common comorbidities within the cohort to determine their significance to BPPV incidence.
      Cohort (n)% or Mean (SD)Unstandardized coefficient95.0% Confidence Interval for BSig.Adjusted R2
      B[lower CI, upper CI]
      Hypertension41

      23.6%
      0.398[-0.080, 0.876]0.1020.02
      Hyperlipidemia67

      38.5%
      -0.000[-0.494, 0.493]0.999-0.012
      Diabetes Mellitus21

      12.1%
      0.351[-0.539, 1.241]0.435-0.004
      Asthma/allergic rhinitis26

      14.9%
      -0.055[-0.816, 0.707]0.886-0.012
      Kidney disease12

      6.9%
      -0.123[-1.081, 0.836]0.800-0.011
      Migraine16

      9.2%
      0.927[0.057, 1.798]0.0370.039
      Heart disease11

      6.3%
      -0.086[-1.045, 0.872]0.858-0.011
      Thyroid disease33

      19.0%
      0.111[-0.488, 0.710]0.713-0.01
      Hearing loss129

      74.6%
      -0.587[-1.252, 0.079]0.0830.027
      On vit. D prior to diagnosis31

      32.6%
      0.300[-0.579, 1.179]0.495-0.012
      Bilateral BPPV19

      11.0%
      -0.380[-1.420, 0.661]0.470-0.006
      Attended vestibular physical therapy121

      70.0%
      0.078[-0.429, 0.585]0.762-0.011
      Currently on vit. D88

      50.9%
      0.359[-0.288, 1.006]0.2730.003
      Severity of episodes (on a scale of 1-10, with 10 being most severe)5.0 (2.7)0.092[-0.064, 0.248]0.2400.009
      Duration of symptoms (how long before first visit had BPPV)14.3 (28.0)0.003[-0.004, 0.011]0.351-0.002
      Vit. D level (ng/mL)31.4 (16.5)-0.007[-0.023, 0.008]0.352-0.001

      3.5 Factors associated with BPPV recurrence

      Regression analyses were performed to find patient characteristics associated with BPPV recurrence rate, with episodes per month as the dependent variable. We did not find any significance with respect to the factors of comorbid diseases, hearing loss, vitamin D supplementation prior to diagnosis, bilateral BPPV, attendance of vestibular therapy, vitamin D supplementation at the time of interview, duration and severity of episodes, or vitamin D serology (Table 4). Migraine was the only independent variable found to be significant on univariate regression (odds ratio=2.53, p=0.037) (Table 4). Hearing loss, hypertension, and migraine were included in the multiple regression analyses because they are common comorbidities with BPPV. [
      • von Brevern M
      • Radtke A
      • Lezius F
      • Feldmann M
      • Ziese T
      • Lempert T
      • et al.
      Epidemiology of benign paroxysmal positional vertigo: a population based study.
      ,
      • Uneri A.
      Migraine and benign paroxysmal positional vertigo: an outcome study of 476 patients.
      ,
      • Von Brevern M
      • Neuhauser H.
      Epidemiological evidence for a link between vertigo and migraine.
      ] Multiple regression also found migraine to be a significant factor with an odds ratio of 2.79 for recurrence of BPPV (p=0.045), suggesting that those with migraines have a 2.79-fold increase in risk of recurrence of BPPV compared to those without. Hearing loss and hypertension were not significant factors on multiple regression analysis (p=0.056, p=0.158, respectively).

      4. Discussion

      Two control groups were utilized in this study. The 2017-2018 NHANES data, a large cohort with serum vitamin D data representative of the general US population, made up the first control group. Our BPPV cohort was significantly older (65.9 vs. 46.7 years) and had fewer males (23.8% vs. 47.7%) than the NHANES control. Our BPPV population demographics are consistent with those in literature, in which the female:male patient ratio can be 1.7-2.7, with mean ages of BPPV diagnosis ranging from 55-60 years.[
      • Hanley K
      • O’ Dowd T.
      Symptoms of vertigo in general practice: a prospective study of diagnosis.
      ,
      • Babac S
      • Djeric D
      • Petrovic-Lazic M
      • Arsovic N
      • Mikic A.
      Why do treatment failure and recurrences of benign paroxysmal positional vertigo occur?.
      ,
      • Agrawal Y
      • Pineault KG
      • Semenov YR.
      Health-related quality of life and economic burden of vestibular loss in older adults.
      ] The racial distribution was significantly different between the two groups (d=0.671[0.519, 0.823]). Notably, only 1.7% of our BPPV cohort were Hispanic, compared to 14.6% of the NHANES group. However, 16.8% of our cohort were African American versus 19.9% in the NHANES group. D'Silva et al. found that African Americans were 1.3 times more likely than Caucasians to have BPPV (p<0.02).[
      • D'Silva LJ
      • Staecker H
      • Lin J
      • Sykes KJ
      • Phadnis MA
      • McMahon TM
      • et al.
      Retrospective data suggests that the higher prevalence of benign paroxysmal positional vertigo in individuals with type 2 diabetes is mediated by hypertension.
      ] However, the majority of our BPPV patients were Caucasian (76.3%). Some of these differences are due to the regional variations in racial distribution but potentially to racial disparities in healthcare access.
      Previous studies have shown migraine, hypertension, hyperlipidemia, and stroke to all be independently associated with BPPV development.[
      • von Brevern M
      • Radtke A
      • Lezius F
      • Feldmann M
      • Ziese T
      • Lempert T
      • et al.
      Epidemiology of benign paroxysmal positional vertigo: a population based study.
      ,
      • Uneri A.
      Migraine and benign paroxysmal positional vertigo: an outcome study of 476 patients.
      ,
      • Von Brevern M
      • Neuhauser H.
      Epidemiological evidence for a link between vertigo and migraine.
      ,
      • D'Silva LJ
      • Staecker H
      • Lin J
      • Sykes KJ
      • Phadnis MA
      • McMahon TM
      • et al.
      Retrospective data suggests that the higher prevalence of benign paroxysmal positional vertigo in individuals with type 2 diabetes is mediated by hypertension.
      ] The common comorbidities present in our BPPV cohort, such as hyperlipidemia (38.5%), hypertension (23.6%), thyroid disease (19.0%), allergic rhinitis (14.9%), and diabetes mellitus (12.1%), were consistent with reports in literature.[
      • Zhu CT
      • Zhao XQ
      • Ju Y
      • Wang Y
      • Chen MM
      • Cui Y.
      Clinical characteristics and risk factors for the recurrence of benign paroxysmal positional vertigo.
      ,
      • Jeong SH
      • Kim JS
      • Shin JW
      • Kim S
      • Lee H
      • Lee AY
      • et al.
      Decreased serum vitamin D in idiopathic benign paroxysmal positional vertigo.
      ,
      • D'Silva LJ
      • Staecker H
      • Lin J
      • Sykes KJ
      • Phadnis MA
      • McMahon TM
      • et al.
      Retrospective data suggests that the higher prevalence of benign paroxysmal positional vertigo in individuals with type 2 diabetes is mediated by hypertension.
      ] Of our patients with migraine, 37.5% had recurrence of BPPV and our regression analysis shows an odds ratio of 2.79 for BPPV recurrence with migraine. Brevern et al. reported a higher odds ratio of 7.5 between migraines and occurence of BPPV.[
      • von Brevern M
      • Radtke A
      • Lezius F
      • Feldmann M
      • Ziese T
      • Lempert T
      • et al.
      Epidemiology of benign paroxysmal positional vertigo: a population based study.
      ] Faralli et al. also found that patients with comorbid migraines had higher BPPV recurrences rates.[
      • Faralli M
      • Cipriani L
      • Del Zompo MR
      • Panichi R
      • Calzolaro L
      • Ricci G.
      Benign paroxysmal positional vertigo and migraine: analysis of 186 cases.
      ] There is no clear pathophysiologic link between migraines and BPPV. It has been proposed that migraines may induce repetitive vasospasm of labyrinthine arteries or alter the trigeminovascular system and affect the vestibulocochlear microcirculation. This leads to dislodging of the utricular otoconia into the semicircular canal, generating BPPV.[
      • von Brevern M
      • Radtke A
      • Lezius F
      • Feldmann M
      • Ziese T
      • Lempert T
      • et al.
      Epidemiology of benign paroxysmal positional vertigo: a population based study.
      ,
      • D'Silva LJ
      • Staecker H
      • Lin J
      • Sykes KJ
      • Phadnis MA
      • McMahon TM
      • et al.
      Retrospective data suggests that the higher prevalence of benign paroxysmal positional vertigo in individuals with type 2 diabetes is mediated by hypertension.
      ,
      • Ishiyama A
      • Jacobson KM
      • Baloh RW.
      Migraine and benign positional vertigo.
      ] Of note, we excluded patients with comorbid vestibular migraine since vestibular migraine patients can have motion sensitivity and dizziness with movements of the head which would make the follow-up with the telephone survey less reliable for a true recurrence of BPPV. Migraine may be an even bigger factor of recurrence that is underestimated in our current paper, as previous studies have found a prevalence of BPPV of 42.3% among a cohort of patients with migraine. [
      • Teixido M
      • Baker A
      • Isildak H.
      Migraine and benign paroxysmal positional vertigo: a single-institution review.
      ]
      Our study found sufficient and higher vitamin D levels in the BPPV cohort compared to the NHANES population, which had insufficient levels (31.4 vs. 26.0 ng/mL). This effect (BPPV vitamin D levels > NHANES) persisted within male, female, and Caucasian (d=0.282 [0.107, 0.457]) subgroups. Interestingly males younger than 70 and females younger than 50 had insufficient levels of vitamin D and lower levels of vitamin D compared to NHANES controls but this did not reach significance. While our BPPV cohort had, on average, sufficient and higher levels of vitamin D compared to the NHANES cohort, subgroup analysis shows that male patients (< 70 years old) in our cohort had insufficient levels whereas females subjects were borderline sufficient starting at the 51-60 subgroup (29.9 ng/mL), with sufficiency in all subgroups >60 years.
      This discrepancy in when gender subgroups achieve sufficient vitamin D levels could be due to females taking supplements at earlier ages than males, as the age of 50 may mark a peri-menopausal time which is when vitamin D supplementation is typically recommended to prevent osteoporosis. Previous studies of women have shown bone mineral density to remain relatively stable through 40s, with a rapid decline starting in a woman's 50s, which further supports the phenomenon seen herein.[
      • Park EJ
      • Joo IW
      • Jang M-J
      • Kim YT
      • Oh K
      • Oh HJ.
      Prevalence of osteoporosis in the Korean population based on Korea National Health and Nutrition Examination Survey (KNHANES), 2008-2011.
      ] Women below the age of 50 are less likely to be on supplements, however the BPPV cohort female subjects aged 30-40 and 41-50 had a more insufficient levels (20.3 ± 3.5 ng/mL and 24.5 ± 7.9 ng/mL, respectively) than their NHANES counterparts (23.8 ± 10.4 ng/mL and 25.5 ± 11.0 ng/mL, respectively). Also our BPPV cohort was made of 173 subjects compared to the 5962 subjects in the NHANES cohort, so it is possible significance could have been achieved if our cohort was a larger size. Differences in racial subgroup vitamin D levels were also noted. While Caucasians had sufficient levels (33 ng/mL), African American were in the insufficient range (24.6 ng/mL) but still higher than NHANES control.
      Given the unclear relationship between vitamin D levels of the NHANES control and BPPV cohort, we repeated the analyses using a locoregional control group to reduce bias from geography, nutritional habits, and demographic variations. We did not find a significant difference in overall vitamin D level between the BPPV and locoregional control (BPPV: 31.5 ± 18.5 ng/mL, locoregional: 32.4 ± 19.0 ng/mL, d=0.051 [-0.161, 0.262]). It is noted that the vitamin D levels of the female age subgroups were increasing with age; starting as a deficient level of 20.3 ng/mL in the 30-40 age group and increasing to a sufficient level of 39.5 ng/mL in the 81-90 age group. As stated above, since women at the age of 50 usually take supplements, this can explain the increasing vitamin D levels. While the above findings were similar with this new control group, significant differences were found in the males ages 51-60 subgroup, with lower, insufficient vitamin D levels in the BPPV group compared to the control. The Institute of Medicine recommends adults up to 70 years to take 600 IU of vitamin D daily and 800 IU of vitamin D in adults older than 70 years.[
      • Lips P
      • Duong T
      • Oleksik A
      • Black D
      • Cummings S
      • Cox D
      • et al.
      A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial.
      ,
      • Meehan M
      • Penckofer S.
      The role of Vitamin D in the aging adult.
      ] This, combined with previous studies showing decline of bone density beginning around 50-60, indicates that our findings may reflect either a period of bone mineral density loss exacerbation or under supplementation.[
      • Khosla S
      • Amin S
      • Orwoll E.
      Osteoporosis in men.
      ,
      • Warming L
      • Hassager C
      • Christiansen C.
      Changes in bone mineral density with age in men and women: a longitudinal study.
      ] Low vitamin D levels within this age range can be attributed to factors not analyzed in this study, such as body habitus, level of physical activity, or diet. No matter how the vitamin D levels became insufficient, this can increase the likelihood of patients getting osteomalacia/osteoporosis or increasing the risk of falls, ultimately increasing the risk of fractures. Vitamin D could also be a specific risk factors in males whereas other factors related to osteoporosis in women may be independent risk factors diluting the effect of vitamin D deficiency in that subgroup. Finally, there is limited data on the turnover rate of otoconia in the inner ear and a vitamin D level at one point in time may not reflect previous deficiencies that were since corrected and could have contributed to BPPV pathology.
      Although a causative link cannot be established through a retrospective study, if a low vitamin D level were related to BPPV in this subgroup, it is reasonable to assume that supplementation may play a role in preventing BPPV onset. For example, Buki et al.[
      • Büki B
      • Ecker M
      • Jünger H
      • Lundberg YW.
      Vitamin D deficiency and benign paroxysmal positioning vertigo.
      ] showed a correlation between supplementation and a decrease in BPPV recurrence. A caveat to that is the fact that in our prospective follow-up, 31 out of 95 successfully contacted patients disclosed taking vitamin D supplements prior to the diagnosis of BPPV (Table 1). Forty percent of those subjects (13/31) were taking <1000 units but 13% (4/31) took > 5000 units and still developed BPPV. Oftentimes patients are unaware their over-the-counter supplements contain vitamin D and are undisclosed.
      A significant difference was also found in the African American males with BPPV, who also had a lower vitamin D level than the locoregional cohort (BPPV: 13.5 ± 1.6 ng/mL, locoregional: 31.5 ± 2.3 ng/mL, d=8.950 [2.446, 15.454]). This could be attributed to the low number of African American males within the data set, but also African Americans are known to have vitamin D deficiency due to eumelanin production. However, the clinical significance of this low vitamin D level is similar to those of the 51-60 year old male BPPV subgroup and more severe deficiency may be an independent risk factor in these subgroups. African Americans and males below the age of 60 may not see the need for vitamin D supplementation. Some studies have found a positive correlation of vitamin D levels with testosterone levels.[
      • Ciccone IM
      • Costa EM
      • Pariz JR
      • Teixeira TA
      • Drevet JR
      • Gharagozloo P
      • et al.
      Serum vitamin D content is associated with semen parameters and serum testosterone levels in men.
      ] As such, this could represent a period of the male aging process in which testosterone production begins to decrease. Another reason for the discrepancy between the two groups could be that there was a lower number of African American males within the cohort. Also, it must be noted that duration of vitamin D supplementation can't be accessed due to the cross-sectional analysis being a snapshot in time. Future studies could involve supplementing vitamin D in BPPV patients found to have low vitamin D serology, with subsequent follow-ups for a period of time to see how many recurrences they have compared to a control group with low vitamin D serology but no supplementation. Previous studies have shown that dose, frequency, and duration of Vitamin D supplementation are all factors influencing vitamin D serology and could be optimized in such a study.[
      • Chao Y-S
      • Brunel L
      • Faris P
      • Veugelers PJ.
      The importance of dose, frequency and duration of Vitamin D supplementation for plasma 25-Hydroxyvitamin D.
      ] It is also possible there are other confounders within these subgroups that are at play that we have yet to identify.
      Theories have been proposed on how vitamin D deficiency may affect the risk of developing BPPV. Otoconia can degenerate due to age, medication exposures, and changes in pH or ionic concentration.[
      • Vibert D
      • Sans A
      • Kompis M
      • Travo C
      • Mühlbauer RC
      • Tschudi I
      • et al.
      Ultrastructural changes in otoconia of osteoporotic rats.
      ,
      • Jang YS
      • Hwang CH
      • Shin JY
      • Bae WY
      • Kim LS.
      Age-related changes on the morphology of the otoconia.
      ,
      • Everett LA
      • Belyantseva IA
      • Noben-Trauth K
      • Cantos R
      • Chen A
      • Thakkar SI
      • et al.
      Targeted disruption of mouse Pds provides insight about the inner-ear defects encountered in Pendred syndrome.
      ,
      • Royaux IE
      • Wall SM
      • Karniski LP
      • Everett LA
      • Suzuki K
      • Knepper MA
      • et al.
      Pendrin, encoded by the pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion.
      ,
      • Stanković KM
      • Brown D
      • Alper SL
      • Adams JC.
      Localization of pH regulating proteins H+ATPase and Cl-/HCO3/- exchanger in the guinea pig inner ear.
      ] For example, the use of streptomycin was noted by Takumida et al. to contribute to otoconia decomposition and recrystallization in guinea pigs but streptomycin discontinuation led to otoconia restoration.[
      • Takumida M
      • De Zhang M
      • Yajin K
      • Harada Y.
      Formation and fate of giant otoconia of the guinea pig following streptomycin intoxication.
      ] Unfortunately, a prospective longitudinal study comparing the prevalence of BPPV in subjects with longstanding vitamin D deficiency versus those without it is unrealistic for logistic and ethical reasons.
      We also investigated the relationship of vitamin D levels with recurrence rates. We found that individuals with BPPV who had no recurrences had a greater vitamin D level than those with ≥1 recurrence (38.0 vs. 29.4 ng/mL). This suggests that vitamin D deficiency may play a role in the natural history/recurrence of BPPV, but we cannot conclude that vitamin D supplementation will decrease BPPV recurrences. It could be that chronic vitamin D deficiency is the major risk factor and if not detected early, supplementation can have minimal effect on otolith degeneration. Previous studies have found severe vitamin D deficiency (<10 ng/mL) to be associated with BPPV recurrence rates.[
      • Talaat HS
      • Abuhadied G
      • Talaat AS
      • Abdelaal MSS.
      Low bone mineral density and vitamin D deficiency in patients with benign positional paroxysmal vertigo.
      ,
      • Talaat HS
      • Kabel AMH
      • Khaliel LH
      • Abuhadied G
      • El-Naga HAERA
      • Talaat AS.
      Reduction of recurrence rate of benign paroxysmal positional vertigo by treatment of severe vitamin D deficiency.
      ]Talaat et al. determined that those with severe vitamin D deficiency had an odds ratio of 4.54 for BPPV recurrence, when compared to patients with vitamin D levels >10 ng/mL.[
      • Talaat HS
      • Kabel AMH
      • Khaliel LH
      • Abuhadied G
      • El-Naga HAERA
      • Talaat AS.
      Reduction of recurrence rate of benign paroxysmal positional vertigo by treatment of severe vitamin D deficiency.
      ] Another study found that vitamin D supplementation significantly lowered recurrence rates (p<0.007).[
      • Jeong S-H
      • Lee S-U
      • Kim J-S.
      Prevention of recurrent benign paroxysmal positional vertigo with vitamin D supplementation: a meta-analysis.
      ] However, we found that patients compliant with supplementation did not have a significantly different rate of BPPV recurrence compared to those who did not take supplements. Furthermore, we did not find vitamin D supplementation to be associated with BPPV recurrence on regression analyses (Table 4). As the guidelines established by Holick et al.[
      • Holick MF
      • Binkley NC
      • Bischoff-Ferrari HA
      • Gordon CM
      • Hanley DA
      • Heaney RP
      • et al.
      Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline.
      ]are based on bone health, and we have found that patients with recurrences of BPPV have insufficient and significantly different (p=0.012) levels of vitamin D (29.4 ng/mL) vs. those with no recurrences (38.0 ng/mL), it is possible that further studies on ideal vitamin D levels specifically for BPPV are warranted. These levels may be less permissive than for bone health. Also, the duration of vitamin D deficiency may play a role as postulated above.
      Within this study, we also analyzed the association of BPPV recurrence rate with the duration and severity of episodes, without any significant findings. Abdelmaksoud et al. found that the number of recurrent BPPV attacks had a negative correlation with vitamin D deficiency, with a significant decrease in recurrence rates 6 months after initiation of vitamin D supplementation with Epley maneuvers versus patients who were treated with the Epley maneuver alone.[
      • Abdelmaksoud AA
      • Fahim DFM
      • Bazeed SES
      • Alemam MF
      • Aref ZF.
      Relation between vitamin D deficiency and benign paroxysmal positional vertigo.
      ] However, we did not replicate these findings. It may reflect an inadequate period of supplementation in our patient population, or too wide a range of variation in supplementation duration, as Abdelmaksoud et al. assessed their patient's symptomatology at 6months follow-up. Or, this could represent a difference in environment as their study was conducted in Egypt and vitamin D levels are dependent on sun exposure. We also asked patients to report their perceived severity of symptoms on a scale of 1-10, with 10 being the most severe. This was also a non-significant factor in BPPV recurrence. Unfortunately, this is a poorly studied variable in BPPV literature. Sheikhzadeh et al. previously found that BPPV severity (called intensity in their study) significantly decreased after 2 months in treated (vitamin D supplemented) and non-treated vitamin D deficient groups, despite vitamin D sufficiency being reached in the groups receiving supplementation.[
      • Sheikhzadeh M
      • Lotfi Y
      • Mousavi A
      • Heidari B
      • Monadi M
      • Bakhshi E.
      Influence of supplemental vitamin D on intensity of benign paroxysmal positional vertigo: A longitudinal clinical study.
      ] However, they did not analyze the correlation of BPPV recurrence rates with perceived severity of symptoms.
      However, it can be assumed that an individual's perception of pain and disability widely varies, and is likely subject to recency bias. The cross-sectional nature of our study limits us from addressing this specific question in more depth.
      This study is limited by the biases of a retrospective review and by a small sample size, which hindered analysis power. While it does not offer definitive answers, it further confirms that the relationship of BPPV with vitamin D levels is complex and not a direct causality. Given the low risk of toxicity with vitamin D supplementation, the prevalence of vitamin D deficiency in the general population, and the physical burden of BPPV, it is reasonable to check vitamin D levels and consider supplementation in patients who have insufficient/borderline insufficient levels. Further research should be done to determine if supplementation of vitamin D could not only increase serum concentrations but also decrease the rate of BPPV episodes; the present study is unable to do so due to limitations of the study design and the shortcomings of medication reconciliation to include vitamin D supplementation in the medication list of patients since these are often over the counter products. For example, on several occasions patients endorsed taking a daily multivitamin, but could not ascertain or did not acknowledge the dose vitamin D within their multivitamin as part of their reported daily vitamin D intake. In addition, screening patients for migraines and treating them could help reduce risk of recurrence since in this study as in others it seems to be a specific risk factor. Controlling for compliance notwithstanding, it remains unclear what threshold cut-off value of vitamin D levels would be considered adequate in this patient population.

      Conflict of Interest

      There are no conflicts of interest.

      Acknowledgements

      This publication was supported by the South Carolina Clinical & Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina (NIH - NCATS Grant Number UL1 TR001450).

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