Effects of Vitamin D and Marine Omega-3 Fatty Acids on Anemia in the Elderly

描述（由申请人提供）：我们建议在新启动的维生素d和omega-3试验（VITAL）中评估具有抗炎特性的维生素D3 （2,000 IU/天）和海洋omega-3脂肪酸（1gm/d二十碳五烯酸[EPA]+840mg/d二十二碳六烯酸[DHA]，比例为1.3:1）对红细胞生成细胞信号传导和老年人贫血发展的影响。任何程度的贫血都被认为是老年人发病率、死亡率和虚弱的重要独立因素。此外，种族似乎是影响贫血患病率的一个重要变量，非洲裔美国人的贫血率明显高于白人。随着21世纪老年人数量预计将达到前所未有的水平，贫血是一个新出现的全球健康问题，对老年人的生活质量产生负面影响，需要不断增加卫生保健资源的分配。老年人贫血的发病机制研究仍然很少，因此，缺乏经证实的预防治疗方法。我们最近发现，维生素D缺乏与老年人中较高的贫血患病率独立相关，特别是那些患有炎症性贫血的人。我们将利用VITAL研究，这是一项随机、双盲、安慰剂对照试验，分析维生素D3和海洋omega-3脂肪酸(？在2万名年龄分别为60岁和65岁的美国男性和女性中，研究了-3 FA)补充剂在癌症和心血管疾病一级预防中的作用，以检验这些干预措施将改善老年人贫血发展的假设。此外，使用VITAL队列的子样本，我们将调查维生素D和/或？FA通过hepcidin和/或促红细胞生成素（EPO）依赖途径影响红细胞生成。我们的目的是确定维生素D和/或w- 3fa补充剂是否通过使用医疗记录审查和由参与者的医生完成的补充问卷来降低诊断贫血的发生率。在我们的子研究中，将从900名受试者中收集干预前和干预后的新鲜样本，这些受试者将在波士顿临床和转化科学中心（CTSC）进行评估。通过对血红蛋白（HgB）、红细胞（RBC）指数、hepcidin和促红细胞生成素的一系列测量，我们将确定维生素D和/或w- 3fa是否能调节炎症介导的HgB水平和促红细胞生成途径的影响。parent VITAL试验的研究基础设施将提供一个独特且具有成本效益的框架，使我们能够检查维生素D和/或w- 3fa补充在减少老年人贫血方面的潜在益处。为了完成基线（预随机化）评估Hgb和红细胞生成途径的新鲜样本，将从波士顿CTSC站点的参与者中收集，至关重要的是，该提案与原VITAL试验（1U01CA138962）的1年入组期平行开始，该试验计划于2011年11月开始。

DESCRIPTION (provided by applicant): We propose to evaluate the impact of vitamin D3 (2,000 IU/day) and marine omega-3 fatty acids (1gm/d eicosapentaenoic acid [EPA]+840mg/d docosahexaenoic acid [DHA], in a 1.3:1 ratio), which have anti- inflammatory properties, on erythropoietic cell signaling and the development of anemia in the elderly in the setting of the newly launched VITamin D and OmegA-3 TriaL (VITAL). Anemia of any degree is recognized as a significant independent contributor to morbidity, mortality, and frailty in the elderly. Furthermore, race appears to be an important variable affecting anemia prevalence, with African-Americans displaying significantly higher rates of anemia than whites. As the number of elderly individuals is expected to reach unprecedented levels in the 21st century, anemia represents an emerging global health problem negatively impacting quality of life in the elderly population and requiring ever increasing allocation of health care resources. The pathogenesis of anemia in the elderly remains poorly studied and, as a consequence, there is a lack of proven preventive therapies. We recently showed that vitamin D deficiency is independently associated with a higher prevalence of anemia in the elderly, particularly among those with anemia of inflammation. We will take advantage of the VITAL study, a randomized, double-blind, placebo-controlled trial analyzing the role of vitamin D3 and marine omega-3 fatty acid (?-3 FA) supplements in the primary prevention of cancer and cardiovascular disease among 20,000 US men and women aged > 60 and > 65 years, respectively, to test the hypothesis that these interventions will ameliorate the development of anemia in the elderly. In addition, using a sub-sample of the VITAL cohort, we will investigate whether vitamin D and/or ?-3 FA influence erythropoiesis via hepcidin- and/or erythropoietin (EPO)-dependent pathways. We aim to determine whether vitamin D and/or w-3 FA supplements reduce the incidence of diagnosed anemia through the use of medical record review and supplementary questionnaires completed by participants' physicians. In our sub-study, fresh samples will be collected pre- and post-intervention from 900 subjects who will be evaluated at the Boston Clinical and Translational Science Center (CTSC). Using serial measurements of hemoglobin (HgB), red blood cell (RBC) indices, hepcidin, and erythropoietin, we will determine whether vitamin D and/or w-3 FA moderate inflammation-mediated effects on Hgb levels and erythropoietic pathways. The research infrastructure of the parent VITAL trial will provide a unique and cost-effective framework that will allow us to examine the potential benefits of vitamin D and/or w-3 FA supplementation in decreasing anemia in an elderly population. In order to complete baseline (pre-randomization) assessments of Hgb and erythropoietic pathways on fresh samples that will be collected from participants at the Boston CTSC site, it is critically important that this proposl begin in parallel to the 1-year enrollment period for the parent VITAL trial (1U01CA138962), scheduled to begin November 2011.