Beneficial effect seen in those with subnormal vitamin D

Benign paroxysmal positional vertigo (BPPV) recurrence was reduced when subnormal vitamin D levels were supplemented, a randomized trial found.

Among patients with a serum vitamin D level below 20 ng/ml, those who took vitamin D 400 IU and 500 mg of calcium carbonate twice daily for 1 year had a lower annual recurrence rate (ARR) than those whose vitamin D level was not supplemented, reported Ji-Soo Kim, MD, PhD, of Seoul National University in Korea, and colleagues.

The ARR for the intervention group was 0.83 (95% CI 0.74-0.92), compared with 1.10 (95% CI 1.00-1.19) for the group without supplementation, they wrote in Neurology.

The incidence rate ratio was 0.76 (95% CI 0.66-0.87; P<0.001) from intention to treat analysis and the number needed to treat was 3.70 (95% CI 2.50-7.14).

“This study provides Class III evidence that for patients with BPPV, vitamin D and calcium supplementation reduces recurrences of BPPV,” Kim and co-authors wrote. “Supplementation of vitamin D and calcium may be considered in patients with frequent attacks of BPPV, especially when serum vitamin D is subnormal.”

In an accompanying editorial, Robin Bigelow, MD, and John Carey, MD, both of Johns Hopkins University, called the study “the best evidence to date in support of vitamin D and calcium supplementation to prevent recurrent BPPV.”

“Patients with BPPV should be screened for vitamin D deficiency in addition to the standard treatment of canalith repositioning maneuvers. If deficient in vitamin D, then consideration should be given to treatment with vitamin D and calcium supplementation (800 IU vitamin D and 1000 mg calcium carbonate per day),” they wrote.

BPPV has a 1-10 year recurrence rate of 15-56% and a high percentage of patients with BPPV experience disruption in daily activities. No therapy prevents recurrence, but recent research found higher prevalence of vitamin D deficiency or insufficiency and decreased bone mineral density in patients with BPPV than in normal controls.

A study of 93 adults with BPPV and vitamin D < 10 ng/ml found less recurrence for those who increased their vitamin D levels to above 10 ng/mL after supplementation. Vitamin D deficiency in the U.S. is common, with a 2011 study reporting a prevalence of about 42% when defined as < 20 ng/ml.

To explore vitamin D supplementation as a vertigo recurrence therapy, Kim and colleagues conducted a prospective, blinded-outcome-assessor, randomized controlled trial of patients with BPPV between December 2013 and May 2017. Patients were randomized to intervention (n=518) or observation (n=532) after a successful treatment with canalith repositioning maneuvers.

Both groups were followed up at 1 year. For the intervention group, serum vitamin D levels were evaluated at baseline, 2 months, and 12 months, and those with vitamin D levels <20 ng/mL were started on supplementation. The observation group had no testing after baseline and no supplementation.

Mean age was about 62 and about 64% were women. BPPV type was posterior in 66.7% of the intervention group and in 64.5% of the observation groups. The mean number of repositioning maneuvers required in both groups was 1.6.

“In this study, both vitamin D and calcium were administered since most consequences of vitamin D deficiency are the results of impaired mineral ion homeostasis, and the cost of combined vitamin D and calcium supplementation adopted in this study was lower than vitamin D supplementation alone in Korea,” the authors noted.

Mean corrected vitamin D level was 24 ng/ml. The proportion of patients with recurrence was lower in the intervention than in the observation group (37.8 vs. 46.7%, P=0.005).

The benefit appeared greater for those with lower vitamin D at the outset: those who began with vitamin D levels <10 ng/mL had a 45% reduction in annual recurrence rate, while those who began with levels of 10-20 ng/mL saw a 14% reduction (P <0.001 for both).

Annual fall and fracture rates did not significantly differ between the groups. Common adverse effects reported were dyspepsia and constipation, and of those supplemented, two patients developed hypercalcemia.

In total, 106 of the 348 patients assigned to supplementation withdrew and 19 patients were lost to follow-up. This represents “36% of those assigned to receive supplementation, whereas only 10% of those in the observational arm withdrew or were lost to follow-up,” the editorialists observed. “This raises concern about ensuring compliance with the recommended supplements.”

Another concern was “what to do with patients in the low normal vitamin D range (20-30 ng/mL), who were not treated in this study,” the editorialists noted. “Subgroup analysis reported 24% fewer recurrences (P=0.05) in those on treatment for vitamin D levels <20 ng/mL compared to those untreated with vitamin D >20 ng/ml.”

“It might seem reasonable conclude that those with vitamin D levels between 20-30 ng/mL could benefit in terms of BPPV prevention,” they added. “However, the supplementation in this study only increased the treated participants’ mean vitamin D level up to 24 ng/mL, yet that was enough to confer benefit. It seems that we can only conclude from the data that correcting a deficit (<20 ng/mL) confers benefit.

Limitations include absence of blinding and placebo control. Misclassification of vertigo, which was established by questionnaire, is possible. Generalizability beyond Korean populations may be limited. Also, the study did not determine the optimal dose of vitamin D.

  1. Benign paroxysmal positional vertigo (BPPV) recurrence was reduced when subnormal vitamin D levels were supplemented, a randomized trial found.

  2. Study data support correcting a vitamin D deficit of <20 ng/ml, the editorialists concluded.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This study was supported by a grant of the Korea Healthcare Technology R&D Project Ministry of Health and Welfare, Republic of Korea.

The authors reported no disclosures relevant to the manuscript. The editorialists reported no disclosures relevant to the manuscript.

An editor’s note in Neurology stated: “We discovered, after accepting this article and well into our production process, that the randomized clinical trial was retrospectively registered by a few weeks.”

Cat ID: 130

Topic ID: 82,130,282,494,730,130,192