PROJECT SUMMARY
Overactive bladder (OAB), the presence of urgency, frequency, and nocturia, is common with aging, as is
urgency urinary incontinence (UUI). These are among the most bothersome lower urinary tract symptoms –
associated with worse mental health, poor physical well-being, and increased falls, fractures, and nursing
home placement. Despite treatment options, many patients do not become symptom-free and discontinue
medications due to side effects or perceived inefficacy. Attention is shifting to possible prevention and early
treatment strategies. Potential benefits of vitamin D may extend to several relevant organ systems, and vitamin
D could act via multiple pathways to reduce lower urinary tract symptoms by improving detrusor activity and
decreasing inflammation. Indeed, evidence emerging from epidemiologic studies indicate that higher vitamin D
levels are associated with decreased risk for OAB and UI.
In this revision application, we will leverage two large, complementary epidemiologic studies – the VITamin D
and omegA-3 TriaL (VITAL, n=25,000 women and men) and the observational Nurses’ Health Studies
(n>100,000 women) -- to conduct a rich exploration of vitamin D and OAB, as well as UUI. In this revision, we
extend research to both OAB and UUI, increasing clinical relevance by broadening the outcomes (previously
only UI) while focusing on symptoms related to detrusor contractility. We also improve innovation by targeting
research in: (1) African Americans (n=2300 in NHS, n=5200 in VITAL), who disproportionately suffer from OAB
and UUI, and have higher prevalence of vitamin D deficiency; and in (2) obese adults (n=34,000 in NHS,
n=7200 in VITAL), who are at higher risk of OAB and UUI, and have lower bioavailability of vitamin D as it is
retained in adipose tissue. Our main Aims are to: 1) assess if vitamin D3 supplementation decreases OAB and
UUI in VITAL, where participants have been assigned to 2000IU/day of vitamin D or placebo for five years, and
in NHS, where observational data are available on a large range of doses, from <400 IU to >800 and >1000
IU/day; and 2) to prospectively assess if higher plasma 25(OH)D levels at baseline are related to a decreased
incidence and progression of UUI in the NHS. In VITAL, where an estimated 50% of participants had
25(OH)D<30ng/mL at baseline, we propose to collect data on OAB and UI symptoms at year 5 by adding new
questions on urgency, frequency, nocturia and urine leakage at the close of the trial. The NHS already includes
extensive UUI data, and we will newly measure baseline vitamin D levels from stored blood samples and add
OAB questions in upcoming follow-up periods. The large samples of African American and of obese adults in
these cohorts uniquely enable important and novel research. The expected outcomes will be to provide
exciting new knowledge regarding vitamin D as a possible convenient, low-cost intervention for
preventing OAB and UUI symptoms and progression among women and men, specifically targeting
high-risk subgroups of African Americans and obese adults.