Hypothesis / aims of study
Despite observational research indicating that vitamin D insufficiency is associated with increased prevalence and incidence of urinary incontinence (UI), almost no randomized trial data are available to indicate whether supplementation with vitamin D reduces UI [1-3]. Given the unique opportunity to test vitamin D supplementation as a possible preventive treatment to reduce UI among older women , we proposed an ancillary analysis of women enrolled in a nationwide vitamin D and omega-3 prevention trial for cancer and cardiovascular disease, the VITamin D and omegA-3 TriaL (VITAL) clinical trial. Our objectives were to evaluate the effects of vitamin D supplementation on UI incidence and prevalence at follow-up at 2 and 5 years after randomization (the years in which UI items were included in participant questionnaires). We hypothesized that older women assigned to vitamin D, especially those with low serum 25-hydroxyvitamin D (25OHD) levels at baseline, will have lower incidence and progression rates of UI than women assigned to placebos.
Study design, materials and methods
We performed a pre-specified ancillary study to VITAL, a 2 x 2 factorial randomized trial conducted among 25,871 participants (including 13,085 women) recruited between November 2011 and March 2014 from all 50 US states. Follow-up was completed in January 2018. Randomized treatments included: 1) vitamin D3 (cholecalciferol) at a dose of 2000 IU/day, and 2) placebo. Validated UI questions were assessed in year 2 and repeated in year 5 at the trial close. The pre-specified outcomes were the prevalence of UI at year 2 and at year 5, along with UI incidence and UI progression from year 2 to year 5, with subgroup analysis for women with low baseline serum levels of 25OHD (<30 ng/mL). Among the 13,085 women randomized, we had UI data from 11,646 women at year 2 and 10,527 at year 5. For the primary analyses, women were analyzed according to their randomization to vitamin D supplementation or placebo using the intention-to-treat principle, along with similar analyses among women with 25OHD biosamples at baseline (n=2,819).
No sociodemographic differences were seen between all women with UI data randomized to vitamin D versus placebo or between women with low serum 25OHD randomized to vitamin D versus placebo at year 2 (mean age = 70.1 years, 29% racial/ethnic minority). At year 2, 64% reported UI, and this increased to 71% at year 5. Supplementation with vitamin D compared to placebo was not associated with lower odds of prevalent UI at year 2 or at year 5 (Table). In women with low serum 25OHD, no differences were found in prevalent UI at year 2 or at year 5 (Table). No differences were found for progression of UI or incidence of UI at year 5, including among women with low serum 25OHD (Table). For all women and women with low serum 25OHD, UI type (urge, stress, mixed, or other) did not differ between randomization groups at year 2 or at year 5 (data not shown).
Interpretation of results
Vitamin D supplementation of 2,000 IU daily in older women was not associated with decreases in UI prevalence after two years or five years, or with decreased progression or incidence of UI, even among women with low 25OHD prior to randomization.