COcoa Supplement and Multivitamins Outcomes Study (COSMOS): Effects on Falls and Physical Performance

摘要 福尔斯和身体功能下降随着年龄的增长而明显增加，并导致受伤、住院和 死亡需要安全、具有成本效益的初级预防战略来减少这些不良后果， 美国人口老龄化基础，临床前和临床研究表明，黄烷醇，一类营养物质存在 在可可中的高浓度，对肌肉和身体表现有良好的影响。黄烷 减少氧化应激和改善线粒体生物合成和肌肉生长的生物标志物。新兴 研究表明，补充可可黄烷醇对身体表现，包括抓地力的潜在好处 老年人的力量和行走速度。然而，目前还没有大规模、长期的随机对照试验 补充黄烷醇对福尔斯、肌肉性能和/或跌倒相关损伤影响的随机对照试验（RCT）。中 可可补充剂和多维生素结局研究（COSMOS）的辅助研究，该研究正在测试 补充可可黄烷醇和/或多种维生素对预防心血管疾病和 癌症，我们提出了第一个大的，安慰剂对照，前瞻性研究，以确定是否补充 黄烷醇可减少福尔斯，改善≥ 65岁女性和≥ 60岁男性的肌肉骨骼健康。在 建议的研究，我们将确定可可黄烷醇补充剂[600毫克/天黄烷醇，包括80毫克， (-)-表儿茶素]和/或多种维生素对以下临床有意义的结果：总体福尔斯下降 COSMOS队列（n= 21，444）和临床子队列（n=603）中的体能。我们将测试以下内容 假设：目标1：在整个COSMOS队列中，补充可可黄烷醇将降低以下风险：（a） 伤害性跌倒，导致前往医疗保健提供者或医院查看病历，以及（B）两次或 每年更多的福尔斯和（c）每年评估的伤害性跌倒（不导致医疗保健使用） 问卷调查目的2：在临床子队列中，可可黄烷醇补充剂将有益于体力 随机化后2年时的性能指标，通过握力、步行速度和短距离进行评估 体能测试组合（包括站立平衡、步行速度和椅子站立）。目标3： 在整个COSMOS队列中，可可黄烷醇补充剂可减少骨折事件， 年度问卷。我们将探讨可可黄烷醇对骨折结果的影响是否是介导的 通过福尔斯和/或骨密度变化。在探索性目标中，我们还将评估多种维生素对 这些相同的结果。测试多种维生素对福尔斯和肌肉骨骼结局影响的RCT如下 缺乏这项辅助研究最大限度地提高了成本效益，以填补有关黄烷醇影响的知识空白 一级预防福尔斯。我们希望拟议的严格的翻译研究将阐明， 补充黄烷醇可改善肌肉骨骼健康并防止福尔斯和体力下降， 美国老年人的数量不断增加，具有临床和公共卫生益处的潜力。

ABSTRACT Falls and decreased physical function increase markedly with age and result in injury, hospitalization, and death. Safe, cost-effective primary prevention strategies are needed to reduce these adverse outcomes in the aging U.S. population. Basic, preclinical, and clinical studies suggest that flavanols, a class of nutrients present in high concentrations in cocoa, have favorable effects on muscle and physical performance. Flavanols decrease oxidative stress and improve biomarkers of mitochondrial biogenesis and muscle growth. Emerging studies show potential benefits of supplemental cocoa flavanols on physical performance, including grip strength and walking speed in older adults. However, there are no large, long-term randomized controlled trials (RCTs) of the effects of supplemental flavanols on falls, muscle performance, and/or fall-related injuries. In an ancillary study to the COcoa Supplement and Multivitamins Outcomes Study (COSMOS), which is testing the effects of supplemental cocoa flavanols and/or multivitamin for the prevention of cardiovascular disease and cancer, we propose the first large, placebo-controlled, prospective study to determine whether supplemental flavanols reduce falls and improve musculoskeletal health in women aged ≥ 65 and men aged ≥ 60. In the proposed study, we will determine effects of a cocoa flavanol supplement [600 mg/d flavanols, including 80 mg (-)- epicatechins] and/or multivitamin on the following clinically meaningful outcomes: falls in the overall COSMOS cohort (n=21,444) and physical performance in a clinic sub-cohort (n=603). We will test the following hypotheses: Aim 1: In the overall COSMOS cohort, cocoa flavanol supplementation will reduce risk of: (a) injurious fall(s) resulting in a visit to a healthcare provider or hospital with medical record review and (b) two or more falls per year and (c) injurious fall(s) (not resulting in healthcare utilization) as assessed by annual questionnaires. Aim 2: In the clinic sub-cohort, cocoa flavanol supplementation will benefit physical performance measures at 2-year post randomization, as assessed by grip strength, walking speed, and Short Physical Performance Battery (a composite of standing balance, walking speed, and chair stands). Aim 3: In the overall COSMOS cohort, cocoa flavanol supplementation reduces incident fractures as assessed by annual questionnaires. We will explore whether effects of cocoa flavanols on fracture outcomes are mediated through falls and/or bone density changes. In exploratory aims we will also assess effects of multivitamins on these same outcomes. RCTs testing effects of multivitamins on falls and musculoskeletal outcomes are lacking. This ancillary study maximizes cost-efficiency to fill gaps in knowledge regarding effects of flavanols for the primary prevention of falls. We expect the proposed, rigorous translational study will elucidate whether supplemental flavanols improve musculoskeletal health and prevent falls and declining physical performance in the increasing number of older adults in the U.S. with potential for clinical and public health benefits.