Daily supplementation with vitamin D and calcium carbonate significantly reduced recurrence of benign paroxysmal positional vertigo (BPPV), especially in patients with low serum vitamin D, results of a randomized trial show.
Previously, canalith repositioning maneuvers had been the only verified treatments of BPPV. Supplementation with vitamin D and calcium may be the first medical treatment that prevents recurrence, investigators note.
Moving forward, clinicians should consider the management of vitamin D deficiency in patients with frequent attacks of BPPV, especially when serum vitamin D levels are low, they write. However, the optimal dose and duration of supplementation are still uncertain, as is the target serum vitamin D level.
Although much of the previous research on vitamin D in patients with BPPV has consisted of anecdotal reports, “this is the first randomized controlled trial of a large number of patients,” assessing these issues, coinvestigator Ji-Soo Kim, MD, PhD, head of neurology at Seoul National University College of Medicine in South Korea, told Medscape Medical News.
The findings were published online August 5 in Neurology.
BPPV is characterized by attacks of dizziness that are caused by a change in head position with respect to gravity. The dislodgment of particles in the ears called otoconia is thought to initiate these attacks. Recurrence of BPPV is common, and the disorder interrupts work and other daily activities for most patients, the researchers note.
Results from previous studies have shown a higher prevalence of vitamin D deficiency or insufficiency in patients with BPPV compared with healthy control groups. Investigators have indicated that vitamin D supplementation prevents recurrences of BPPV, but their studies have not been prospective or controlled.
For this report, researchers conducted a randomized controlled trial to determine whether supplementation with vitamin D and calcium prevents recurrence of BPPV.
They enrolled patients from eight university hospitals in South Korea. Eligible participants were age 18 years or older and had confirmed BPPV that had been treated successfully with canalith repositioning maneuvers. Patients who planned to use vitamin D or calcium therapy were excluded, as were women who were pregnant.
From December 2013 to May 2016, 1491 patients were screened for eligibility and 1050 patients were included in the study. The participants were randomly assigned in equal groups to oral vitamin D at doses of 400 IU twice daily plus 500 mg of calcium carbonate twice daily, or to observation.
Patients in the intervention group underwent evaluation of serum 25-hydroxyvitamin D [25(OH)D], calcium, phosphorus, and parathyroid hormone levels. Patients in the observation group underwent follow-up without blood tests. They were not allowed to take vitamin D or calcium supplements during follow-up, which lasted for 1 year.
The primary outcome measure was total number of BPPV recurrences per patient at least 1 month after resolution of the initial attack (the annual recurrence rate of BPPV). Proportion of patients with recurrences during follow-up, changes in serum vitamin D level, annual fall rate, annual fracture rate, and quality of life as measured by the UCLA Dizziness Questionnaire were secondary outcome measures.
Patients were asked to call the study center and visit the nearest clinic if they suspected a recurrence of BPPV. They underwent monthly phone interviews about episodes of vertigo and secondary endpoints. Investigators also measured participants’ serum calcium at 2 months and regularly recorded adverse events.
In all, 445 patients in the intervention group and 512 in the observation group completed at least 1 month of follow-up. The median follow-up duration was 365 days in the intervention group and 362 days in the observation group. The proportion of patients who completed a year of follow-up was 79.8% and 92.2%, respectively.
Results showed that supplementation with vitamin D and calcium was associated with a significant reduction in BPPV recurrences.
The number of recurrences per one-person year was 0.83 in the intervention group and 1.10 in the observation group. This yielded an incidence rate ratio (IRR) of 0.76 and a reduction in the annual recurrence rate of 0.27 with supplementation.
The preventive effect was even more pronounced among patients with decreased serum vitamin D of less than 20 ng/mL at baseline.
Subgroup analyses indicated that most clinical variables did not influence the protective effect of supplementation. The exceptions to this observation were age younger than 65 years, absence of vascular risk factors, and history of migraine.
A larger proportion of patients in the observation group had BPPV recurrences (46.7%) compared with the intervention group (37.8%). Among treated patients, serum vitamin D levels increased from 13.3 ng/mL at baseline to 24.4 ng/mL at 2 months and 24.2 ng/mL at 1 year.
The rates of unexpected falls and fractures did not differ between the groups, and both groups had a significant improvement in quality of life.
The most common adverse events in the intervention group were dyspepsia
(n = 10), constipation (n = 5), and edema (n = 3). Two patients discontinued calcium supplementation because of hypercalcemia. In addition, three deaths occurred (all in the control group) but were not related to the use of study medication.
The investigators note that BPPV and atypical or vestibular migraine have symptoms in common.
“Patients with migraine may show positional vertigo and nystagmus that may mimic BPPV. Otherwise, the mechanism of BPPV may be different,” Kim said.
Participants in this study with a diagnosis of migraine who did not benefit from supplementation may in fact have vestibular migraine, he added.
The researchers plan to conduct another randomized controlled trial that includes a placebo group to evaluate the effectiveness of higher-dose supplementation or monthly injection of vitamin D, Kim reported.
An editor’s note on the paper says this about the publication:
“We discovered, after accepting this article and well into our production process, that the randomized clinical trial was retrospectively registered by a few weeks. While this might seem like a minor detail, we think that the issue of prospective registration is crucially important to ensure unbiased reporting of clinical trials. Because of the late stage at which we discovered this oversight, we did not think that it would be fair to reject this paper, but we asked the authors to clarify the registration status of this study. We strive to identify any such irregularity earlier in the process.”
The study was funded by the Republic of Korea’s Ministry of Health and Welfare through a grant from the Korea Healthcare Technology R&D Project. The researchers have disclosed no relevant financial relationships.
Neurology. Published online August 5, 2020. Abstract