Vitamin D and Fish Oil for Autoimmune Disease and Inflammation

维生素 D 和鱼油治疗自身免疫性疾病和炎症

• 批准号: 10172848
• 负责人: Karen H Costenbader
• 金额: $ 61.35万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-07 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10172848
• 关键词: Acids; Address; Affect; African American; Anti-Inflammatory Agents; Attention; Autoantibodies; Autoimmune; Autoimmune Diseases; Autoimmunity; Award; Biological; Biological Assay; Biological Markers; Blood; Blood Banks; Blood specimen; CD59 Antigen; Cholecalciferol; Chronic; Clinical Data; Cohort Studies; Data; Dinoprostone; Disease; Docosahexaenoic Acids; Docosahexaenoic acid supplement; Double-Blind Method; Eicosanoid Production; Eicosanoids; Eicosapentaenoic Acid; Enrollment; Ensure; Exposure to; Fish Oils; Funding; Generations; Grant; Health Benefit; Health Care Costs; Heterogeneity; Human; Incidence; Individual; Inflammation; Inflammation Mediators; Inflammatory; Infrastructure; Intake; Interdisciplinary Study; Interleukin-6; Investigation; Laboratories; Laboratory Study; Leukotriene B4; Lipids; Liquid Chromatography; Literature; Long-Term Effects; Mass Spectrum Analysis; Mediator of activation protein; Medical; Medical Records; Medicare claim; Modification; Morbidity - disease rate; Nutritional; Nutritive Value; Obesity; Omega-3 Fatty Acids; Onset of illness; Parents; Participant; Pathogenesis; Peptides; Physicians; Placebos; Plasma; Population; Premature Mortality; Prevention; Prevention trial; Preventive; Public Health; Randomized; Randomized Clinical Trials; Receptors, Tumor Necrosis Factor, Type II; Reporting; Resolution; Risk; Running; Smoker; Smoking; Specific qualifier value; Subgroup; Supplementation; TNFRSF1B gene; Testing; Time; United States National Institutes of Health; Vitamin D; Woman; Work; aged; autoimmune inflammation; base; case finding; cohort; design; dietary supplements; disability; disorder prevention; double-blind placebo controlled trial; eligible participant; epidemiology study; exhaust; fatty acid supplementation; follow-up; four-arm trial; improved; innovation; knee pain; lipid mediator; lipidomics; liquid chromatography mass spectroscopy; men; novel; pill; premature; prevent; protective effect; randomized placebo controlled trial; recruit; side effect; success; systemic inflammatory response; treatment group

ABSTRACT Autoimmune diseases affect ~ 5% of the U.S. population and carry a high burden of morbidity, health care costs, disability, and premature mortality. In the first cycle of this award, we leveraged an innovative nationwide NIH-funded double-blind, placebo-controlled randomized trial, VITAL, to test the effects of vitamin D (vitamin D3 [cholecalciferol]) and marine omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements upon the risk of incident autoimmune disease and changes in biomarkers of systemic inflammation. Data from laboratory studies, observational epidemiologic research, and small prevention trials strongly suggest that these nutritional agents have anti-inflammatory and immunomodulating benefits. Popular enthusiasm for vitamin D and fish oil supplements underscores the urgent need for rigorous testing. We have recruited, randomized, and are following 25,874 VITAL participants, men aged ≥50 and women aged ≥55 nationwide, including 20% African Americans. Following a 3 month run-in, eligible participants were randomly assigned to one of four treatment groups: vitamin D3 (2000 IU/d) and fish oil (EPA+DHA, 1 g/d); vitamin D3 and fish oil placebo; placebo vitamin D3 and fish oil; and placebo vitamin D3 and placebo fish oil. At yearly intervals, all participants receive a new pill supply, are asked about compliance and side effects, and report incident autoimmune diseases. A physician endpoints committee has confirmed 444 incident autoimmune disease cases by medical record review to date. In a randomly selected subcohort of 1634 VITAL participants, blood samples have been assayed for changes in C-reactive peptide, interleukin-6, and tumor necrosis factor- receptor 2 in all four trial arms. With this renewal grant, we will complete the 5 pre-specified years and a 2 year observational extension, critically important given the long latency of autoimmune disease onset. Continued follow-up will improve statistical power for detecting preventive effects on autoimmune disease incidence, and will enable investigations of effects over time and effect modification by baseline factors and biomarkers. We hypothesize that there will be a delayed reduction in autoimmune disease, and that the largest preventive effects will be among those with high systemic inflammation, including the obese and those with elevated baseline biomarkers of inflammation. In this renewal, we also will test for changes in “Specialized Pro- Resolving Mediators” (SPM), novel omega-3 fatty acid-dependent lipids responsible for inflammation resolution. We will employ cutting-edge quantitative liquid chromatography-tandem mass spectroscopy to extend understanding of the biological mechanisms by which omega-3 fatty acids influence inflammation resolution and potentially autoimmune disease pathogenesis. Given the ongoing NIH-funded VITAL trial infrastructure, our strong multidisciplinary research team, and success with prior large mail-based trials and cohort studies, with continued funding these investigations will furnish robust and definitive results with important public health ramifications.

摘要 自身免疫性疾病影响约5%的美国人口，并带来很高的发病率、医疗保健负担 费用、残疾和过早死亡。在这个奖项的第一个周期中，我们利用了全国范围内的创新 NIH资助的双盲、安慰剂对照随机试验，VITAL，以测试维生素D(维生素)的效果 D3[胆钙化醇])和海洋欧米茄-3脂肪酸(二十碳五烯酸[EPA]+二十二碳六烯酸 [DHA])补充剂对发生自身免疫性疾病的风险和系统性疾病生物标记物的变化 发炎。来自实验室研究、观察性流行病学研究和小型预防试验的数据 强烈表明这些营养剂具有抗炎和免疫调节的好处。受欢迎 对维生素D和鱼油补充剂的热情突显了严格检测的迫切需要。我们有 招募、随机并跟踪25,874名重要参与者，其中男性年龄为≥50岁，女性年龄为≥55岁 全国范围内，包括20%的非裔美国人。经过3个月的磨合，合格的参与者被随机 分配到四个治疗组之一：维生素D3(2000IU/d)和鱼油(EPA+DHA，1g/d)； 鱼油安慰剂；安慰剂维生素D3和鱼油；以及安慰剂维生素D3和安慰剂鱼油。每隔一年， 所有参与者都会收到新的药片供应，被问及遵从性和副作用，并报告事件 自身免疫性疾病。医生终结点委员会已确认444例自身免疫性疾病 到目前为止通过病历审查的病例。在随机选择的1634名重要参与者中，血液 对样本进行了C反应肽、白介素6和肿瘤坏死因子的变化检测。 在所有四个试验臂中都有受体2。有了这笔续期拨款，我们将完成预先指定的5年和2年 鉴于自身免疫性疾病的发病潜伏期较长，观察范围的扩大至关重要。续 后续行动将提高检测自身免疫性疾病发病率预防效果的统计能力，以及 将能够调查随时间变化的影响以及通过基线因素和生物标志物进行的影响修正。我们 假设自身免疫性疾病会延迟减少，最大的预防 影响将发生在那些全身炎症程度较高的人中，包括肥胖者和增高者。 炎症的基线生物标志物。在此次续订中，我们还将测试“专业专业人员- 与炎症有关的新型omega-3脂肪酸依赖脂类--“分解介质”(SPM) 决议。我们将使用尖端的定量液相色谱-串联质谱学来 加深对omega-3脂肪酸影响炎症的生物学机制的理解 解决和潜在的自身免疫性疾病的发病机制。鉴于正在进行的由NIH资助的VITAL试验 基础设施，我们强大的多学科研究团队，以及之前基于邮件的大型试验和 队列研究，在继续资助的情况下，这些调查将提供强有力的和明确的结果 对公共卫生的重要影响。

项目成果

Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer.

海洋N-3脂肪酸和心血管疾病和癌症的预防。

• DOI: 10.1056/nejmoa1811403
• 发表时间: 2019-01-03
• 期刊: The New England journal of medicine
• 作者: Manson JE;Cook NR;Lee IM;Christen W;Bassuk SS;Mora S;Gibson H;Albert CM;Gordon D;Copeland T;D'Agostino D;Friedenberg G;Ridge C;Bubes V;Giovannucci EL;Willett WC;Buring JE;VITAL Research Group
• 通讯作者: VITAL Research Group

Disclosure of Personalized Rheumatoid Arthritis Risk Using Genetics, Biomarkers, and Lifestyle Factors to Motivate Health Behavior Improvements: A Randomized Controlled Trial.

• DOI: 10.1002/acr.23411
• 发表时间: 2018-06
• 期刊: Arthritis care & research
• 影响因子: 4.7
• 作者: Sparks JA;Iversen MD;Yu Z;Triedman NA;Prado MG;Miller Kroouze R;Kalia SS;Atkinson ML;Mody EA;Helfgott SM;Todd DJ;Dellaripa PF;Bermas BL;Costenbader KH;Deane KD;Lu B;Green RC;Karlson EW
• 通讯作者: Karlson EW

Geographic Region, Racial/Ethnic Disparities, and Late-Life Depression: Results From a Large US Cohort of Older Adults.

地理区域，种族/种族差异和晚期抑郁症：来自美国大批老年人的大量抑郁症。

• DOI: 10.1016/j.jagp.2021.11.010
• 发表时间: 2022-06
• 期刊: The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry
• 作者: Vyas CM;Reynolds CF 3rd;Donneyong M;Mischoulon D;Chang G;Cook NR;Manson JE;Okereke OI
• 通讯作者: Okereke OI

Association of Race and Ethnicity With Late-Life Depression Severity, Symptom Burden, and Care.

种族和民族与晚年抑郁症严重程度、症状负担和护理的关系。

• DOI: 10.1001/jamanetworkopen.2020.1606
• 发表时间: 2020
• 期刊: JAMA network open
• 影响因子: 13.8
• 作者: Vyas,ChiragM;Donneyong,Macarius;Mischoulon,David;Chang,Grace;Gibson,Heike;Cook,NancyR;Manson,JoAnnE;Reynolds3rd,CharlesF;Okereke,OliviaI
• 通讯作者: Okereke,OliviaI

Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial.

• DOI: 10.1136/bmj-2021-066452
• 发表时间: 2022-01-26
• 期刊: BMJ (Clinical research ed.)
• 作者: Hahn J;Cook NR;Alexander EK;Friedman S;Walter J;Bubes V;Kotler G;Lee IM;Manson JE;Costenbader KH
• 通讯作者: Costenbader KH