A small number of observational epidemiologic studies indicate that vitamin D insufficiency is associated with increased prevalence and incidence of urinary incontinence (UI) and overactive bladder (OAB) in men but limited clinical trial data are available regarding supplementation with vitamin D and UI or OAB [1-2]. We leveraged a unique opportunity to test vitamin D supplementation as a possible preventive treatment to reduce UI and OAB among older men, in an ancillary study of men enrolled in a nationwide vitamin D and omega-3 prevention trial for cancer and cardiovascular disease, the VITamin D and omegA-3 TriaL (VITAL) [3]. Our objectives were to evaluate the effects of vitamin D supplementation on UI and OAB prevalence after 2 and 5 years of supplementation, including secondary analysis of men with low serum vitamin D levels prior to randomization. We hypothesized that older men assigned to vitamin D would have lower prevalence of UI and OAB than men assigned to placebo after 2 and 5 years.

We performed a pre-specified ancillary study to VITAL, a 2 x 2 factorial randomized trial conducted among 25,871 men and women recruited between November 2011 and March 2014 from all 50 US states. Follow-up was completed in January 2018. Randomized vitamin D treatments included: 1) vitamin D3 (cholecalciferol) at a dose of 2000 IU/day, and 2) placebo. Validated UI questions (frequency and type) and OAB questions (urgency, frequency, and nocturia) were assessed in year 2 and year 5 at the trial close. The pre-specified outcomes were the prevalence of UI at year 2 and year 5, along with OAB assessed only at year 5, with subgroup analysis for men with low pre-randomization serum levels of vitamin D (25OHD<30 ng/mL). Among the 12,786 men randomized, UI data were available from 11,486 at year 2, 10,474 men at year 5; with OAB data on 5,732 at year 5 (OAB items were added late in the questionnaire follow-up). For the primary analyses, men were analyzed according to their randomization to vitamin D supplementation or placebo using the intention-to-treat principle, along with similar analyses among men with 25OHD biosamples at baseline.

As expected, no sociodemographic differences were seen between men randomized to vitamin D versus placebo (mean age = 68 years, 24% racial/ethnic minority), including the subset with low plasma 25OHD. At year 5, 41% reported UI and 35% reported OAB. Supplementation with vitamin D compared to placebo was not associated with lower odds of prevalent UI at year 2 and year 5 or prevalent OAB at year 5 (Table). In men with low 25OHD, no differences were found in prevalent UI, although there was a borderline significant decrease in OAB prevalence (OR 0.83, 95% CI 0.69-1.01, p=0.06, Table). For all men and men with low 25OHD, UI type (urge, stress, mixed, or other) did not differ between randomization groups, and prevalence of OAB combined with UI did not differ either (data not shown).

Vitamin D supplementation of 2,000 IU daily in men was not associated with decreased prevalence of any UI, weekly UI or OAB symptoms. Among men with low 25OHD levels, there was no decrease in prevalence of any UI and weekly UI. However, among men with low 25OHD, we found a non-significant trend toward decreased odds of OAB symptoms at 5 years, which deserves further evaluation.

This study provides novel clinical trial data that vitamin D supplementation compared to placebo does not substantially affect UI or OAB in older men after 2 and 5 years of treatment.

Vaughan CP, Johnson TM, II, Goode PS, Redden DT, Burgio KL, Markland AD. Vitamin D, Urinary Incontinence, and Lower Urinary Tract Symptoms among US Men: Results from the National Health and Nutrition Examination Survey.  Urology. 2011 Dec;78(6):1292-7.
Vaughan CP, Tangpricha V, Motahar-Ford N, Goode PS, Burgio KL, Allman RM, Daigle SG, Redden DT, Markland AD. Vitamin D and incident urinary incontinence in older adults. Eur J Clin Nutr 2016.
Manson JE, Cook NR, Lee IM, et al. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med. 2019;380(1):33–44