Role of Vitamin D in the Prevention and Progression of Urinary Incontinence

项目总结 膀胱过度活动(OAB)，即紧迫感、频率和夜尿症的存在，在年龄增长时很常见，也是如此 急性尿失禁(UUI)。这些都是最令人烦恼的下尿路症状之一- 精神健康状况差，身体健康状况差，跌倒、骨折和护理增多 家庭安置。尽管有多种治疗方法可供选择，但许多患者并未完全摆脱症状并停止治疗。 因副作用或感觉无效而服用的药物。注意力正在转移到可能的预防和早期 治疗策略。维生素D的潜在益处可能延伸到几个相关的器官系统，以及维生素 D可以通过多个途径发挥作用，通过改善逼尿肌活动来减轻下尿路症状，并 消炎消炎。事实上，来自流行病学研究的证据表明，较高的维生素D 水平与OAB和UI的风险降低相关。 在这个修订应用中，我们将利用两个大型的、互补的流行病学研究--维生素D Omega-3试验(VITAL，n=25,000名女性和男性)和观察性护士健康研究 (N&GT；100,000女性)--对维生素D和OAB以及尿路感染进行丰富的探索。在这次修订中，我们 将研究扩展到OAB和UUI，通过扩大结果提高临床相关性(以前 仅限UI)，同时关注与逼尿肌收缩相关的症状。我们还通过有针对性地提高创新能力 研究领域：(1)非裔美国人(NHS中2300人，VITAL中n=5200人)，他们患有不成比例的OAB 和尿失禁，并有更高的维生素D缺乏患病率；以及(2)肥胖成年人(NHS中的34,000人， N=7200人)，他们患OAB和UUI的风险更高，维生素D的生物利用度更低 残留在脂肪组织中。我们的主要目标是：1)评估补充维生素D3是否能降低OAB和 VITAL中的UUI，参与者被分配到每天2000IU的维生素D或安慰剂，为期五年，以及 在NHS中，可获得大范围剂量的观测数据，从&lt；400Iu到&gt；800和&gt；1000 2)前瞻性评估基线时较高的血浆25(OH)D水平是否与 不稳定性尿失禁在国民健康保险制度中的发生和发展。在VITAL，估计有50%的参与者有 25(OH)D&lt；30 ng/毫升的基线，我们建议在第5年通过添加新的 关于试验结束时的紧迫性、频率、夜尿和尿漏的问题。国民健康保险制度已经包括 大量的UUI数据，我们将从存储的血液样本中新测量基线维生素D水平，并添加 在即将到来的后续阶段中提出的OAB问题。非洲裔美国人和肥胖成年人的大样本 这些队列独特地使重要和新颖的研究成为可能。预期结果将是提供 关于维生素D作为一种可能的方便、低成本的干预措施的令人兴奋的新知识 预防女性和男性OAB和UUI症状和进展，特别是针对 非洲裔美国人和肥胖成年人的高危亚群。

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.