Folic Acid, B-Vitamins and AMD: Blood and Diet-based Studies

叶酸、B 族维生素和 AMD：基于血液和饮食的研究

• 批准号: 8129563
• 负责人: WILLIAM G CHRISTEN
• 金额: $ 20.96万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8129563
• 关键词: Address; Age related macular degeneration; Animal Model; Antioxidants; Archives; Ascorbic Acid; Beta Carotene; Biological Markers; Blood; Blood specimen; C-reactive protein; Cardiovascular Diseases; Cardiovascular system; Case-Control Studies; Cataract; Cell Adhesion Molecules; Choroidal Neovascularization; Complement Factor H; Confidence Intervals; Data; Data Quality; Databases; Diagnosis; Diet; Dietary intake; Effectiveness; Evaluation; Event; Fibrinogen; Folate; Folic Acid; Functional disorder; Funding; Future; Genetic; Genetic Polymorphism; Health; Health Professional; Homocysteine; Homocystine; Human; Inflammation; Interleukin-6; Knowledge; Light; Link; Measurement; Measures; Mediating; Meta-Analysis; Methodology; Methylenetetrahydrofolate reductase (NADPH); Micronutrients; National Eye Institute; National Heart, Lung, and Blood Institute; Observational Study; Participant; Pathogenesis; Persons; Physicians; Plasma; Population; Prevention; Prospective Studies; Randomized; Relative Risks; Reporting; Research Design; Resources; Risk; Risk Factors; Risk Reduction; Specimen; Subgroup; Supplementation; Testing; Thiamine; United States National Institutes of Health; Variant; Vitamin B 12; Vitamin B Complex; Vitamin B6; Vitamin E; Vitamins; Woman; Women' s Health; active method; aged; arm; base; cardiovascular disorder risk; case control; cohort; cost; cytokine; design; double-blind placebo controlled trial; experience; follow-up; genetic variant; high risk; inflammatory marker; interest; men; prospective; randomized trial; treatment effect

DESCRIPTION (provided by applicant): This application proposes to conduct several timely and cost-efficient blood-based and diet-based studies to expand upon recent randomized trial findings for age-related macular degeneration (AMD) in the Women's Antioxidant Folic Acid Cardiovascular Study (WAFACS). WAFACS was a randomized, double-blind, placebo-controlled trial conducted among female health professionals aged 40 years or older who were at high risk of cardiovascular events. The findings for AMD in WAFACS, based on an average of 7.3 years of treatment and follow-up of 5,205 women in the folic acid arm, indicate a statistically-significant 34% reduced risk of confirmed AMD (55 cases vs. 82 cases) for those assigned to active treatment with folic acid (2.5 mg/d), vitamin B6 (50 mg/d), and vitamin B12 (1 mg/d). Supplementation with folic acid and B vitamins is known to reduce plasma levels of homocysteine. Therefore, a primary aim of this proposal is to address the causal relevance of homocysteine to AMD by conducting the first prospective studies of plasma homocysteine and AMD in women and men utilizing available data from WAFACS, the Women's Health Study, and Physicians' Health Study II. A total of 829 cases of confirmed AMD have been documented among participants with baseline blood specimens in these cohorts and are available for analysis. We will also utilize archived blood specimens collected at baseline and at follow-up for 300 participants in WAFACS to examine the effect of folic acid/B6/B12 supplementation on four biomarkers of inflammation and endothelial dysfunction found to be associated with risks of AMD in observational studies. Finally, we will explore whether the reduced risk of AMD observed in WAFACS reflects the homocysteine-lowering effect of folic acid and B vitamins by utilizing archived blood specimens collected at baseline to contrast the magnitude of risk reduction in women with baseline homocysteine level above, as compared to below, the median value. We will also explore the modifying effect of baseline levels of plasma folate, vitamin B6, and vitamin B12 on the effectiveness of folic acid/B6/B12 supplementation. This proposal represents an extraordinarily cost-efficient opportunity to extend the promising overall findings for AMD in WAFACS to important blood-based and diet-based subgroups. The information derived from these studies will address important gaps in knowledge regarding the homocysteine-AMD hypothesis, and should contribute to the efficient design of future trials in other populations to critically evaluate the possible beneficial effect of folic acid and B vitamin supplementation in AMD.

描述（由申请人提供）：本申请提议进行几项及时且具有成本效益的基于血液和饮食的研究，以扩展女性抗氧化剂心血管研究中与年龄相关的黄斑变性（AMD）的最新随机试验结果（AMD） （WAFACS）。 WAFACS是一项随机，双盲的，安慰剂对照试验，对40岁或40岁以上的女性卫生专业人员进行了高风险患心血管事件的风险。 WAFAC中AMD的发现，基于叶酸组中的5,205名妇女的平均治疗和随访，表明统计学上有34％的34％降低了确认AMD的风险（55例，82例）分配给叶酸（2.5 mg/d），维生素B6（50 mg/d）和维生素B12（1 mg/d）的活性治疗。众所周知，补充叶酸和B维生素可降低同型半胱氨酸的血浆水平。因此，该提案的主要目的是通过对妇女健康研究WAFACS的可用数据，以及医生的健康研究II进行首次对血浆同型半胱氨酸和AMD进行的前瞻性研究来解决同型半胱氨酸与AMD的因果关系。 。在这些同类中，总共有829例已确认AMD病例已记录在基线血液标本中，可用于分析。我们还将利用300名WAFAC参与者在基线和随访中收集的存档血样，以检查叶酸/B6/B12补充对四种炎症和内皮功能障碍的生物标志物的影响研究。最后，我们将探讨WAFAC中观察到的AMD风险的降低是否反映了叶酸和B族维生素的同型半胱氨酸降低的作用，该作用是利用基线收集的存档血液标本来对比上面的基线同型物体同类水平的女性的风险降低，例如与以下相比，中值。我们还将探讨血浆叶酸，维生素B6和维生素B12基线水平对补充叶酸/B6/B12的有效性的修改作用。该提案代表了一个极高的成本效益的机会，可以将WAFAC中AMD的有希望的总体发现扩展到重要的基于血液和饮食的亚组。从这些研究中得出的信息将解决有关同半胱氨酸AMD假设的知识的重要差距，并应为其他人群中未来试验的有效设计有助于认真评估AMD中叶酸和B维生素补充剂的可能有益作用。