A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis

Abstract

Objective: Low serum vitamin D levels have been associated with increased prevalence of the reproductive tract condition bacterial vaginosis (BV). The objective of this trial was to evaluate the effect of high-dose vitamin D supplementation on BV recurrence.

Study design: This randomized, placebo-controlled, double-blinded trial enrolled 118 women with symptomatic BV from an urban sexually transmitted disease clinic (clinicaltrials.gov registration NCT01450462). All participants received 500 mg of oral metronidazole twice daily for 7 days. Intervention participants (n = 59) also received 9 doses of 50,000 IU of cholecalciferol (vitamin D3) over 24 weeks; control women (n = 59) received matching placebo. Recurrent BV was assessed via Nugent scoring after 4, 12, and 24 weeks. We assessed the effect of the intervention using an intention-to-treat approach, fitting Cox proportional hazards models to evaluate recurrent BV over the follow-up period.

Results: Most participants (74%) were black, with a median age of 26 years. Median presupplementation serum 25-hydroxyvitamin D [25(OH)D] was similar across randomization arms: 16.6 ng/mL in the vitamin D arm and 15.8 ng/mL in the control arm. At trial completion, median 25(OH)D among women receiving vitamin D was 30.5 ng/mL, vs 17.8 ng/mL in control women; 16% of women receiving vitamin D and 57% receiving placebo remained vitamin D deficient (<20 ng/mL). BV prevalence among women randomized to vitamin D was very similar to those randomized to placebo at the 4- and 12-week visits, but by the 24-week visit, BV prevalence was 65% among women in the vitamin D arm and 48% among control women. BV recurrence was not reduced by vitamin D supplementation (intention-to-treat hazard ratio, 1.11; 95% confidence interval, 0.68-1.81). Among women experiencing recurrent BV, median time to recurrence was 13.7 weeks in the vitamin D arm and 14.3 weeks in the control arm.

Conclusion: Women receiving vitamin D experienced significant increases in serum 25(OH)D, but this increase was not associated with decreased BV recurrence in this high-risk sexually transmitted disease clinic population.

Keywords: bacterial vaginosis; randomized controlled trial; sexually transmitted disease clinic; vitamin D.

Conflict of interest statement

Disclosure statement of any potential conflicts of interest:

Bio-Tech Pharmacal (Fayetteville, AR) donated both the vitamin D and placebo products used in this trial. Bio-Tech Pharmacal had no involvement in any other aspect of the research, including protocol development, data collection, analysis, manuscript writing or any other component of trial implementation or interpretation. ANT, PCR, KSF, JA, ME, JAD, RNF, MWR, MAK and RDJ have otherwise no commercial or other association that might pose a conflict of interest.

Copyright © 2014 Elsevier Inc. All rights reserved.

Figures

Figure 1

Flow diagram of the screening, enrollment, follow-up, and analysis of study participants.

Figure 2

Median and interquartile range of serum vitamin D levels over the follow-up period, by randomization group.

Figure 3

Prevalence and 95% confidence intervals of bacterial vaginosis over the follow-up period, by randomization group.

Figure 4

Kaplan-Meier survival curve of time to BV recurrence, by randomization group.