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

摘要 跌倒和身体机能下降随着年龄的增长而显著增加，并导致受伤、住院和 死亡。需要安全、成本效益高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，黄烷醇是一种存在的营养物质。 在高浓度的可可中，对肌肉和身体表现有良好的影响。黄烷醇 减少氧化应激，改善线粒体生物发生和肌肉生长的生物标志物。新兴 研究表明，补充可可黄烷醇对包括握力在内的身体表现有潜在的好处 老年人的力量和步行速度。然而，目前还没有大规模的长期随机对照试验。 (RCT)补充黄烷醇对跌倒、肌肉表现和/或跌倒相关伤害的影响。在一个 可可补充剂和多种维生素结果研究(COSMOS)的辅助研究，该研究正在测试 补充可可黄烷醇和/或复合维生素对预防心血管疾病和 癌症，我们提出了第一项大型、安慰剂对照的前瞻性研究，以确定补充 在≥65岁的女性和≥60岁的男性中，黄烷醇可以减少跌倒并改善肌肉骨骼健康。在 拟议的研究，我们将确定可可黄醇补充剂的效果[600毫克/天黄烷醇，包括80毫克 (-)-表儿茶素]和/或复合维生素对以下临床有意义的结果的影响：总体下降 COSMOS队列(n=21,444)和临床亚队列中的体能(n=603)。我们将测试以下内容 假设：目标1：在整个宇宙队列中，补充可可黄醇将降低以下风险：(A) 伤害性跌倒(S)导致就诊医疗保健提供者或医院并进行病历审查，以及(B)两次或 每年更多的跌倒和(C)损伤性跌倒(S)(不导致医疗保健利用) 问卷调查。目的2：在临床亚队列中，补充可可黄醇将有益于身体健康 随机化后2年的绩效测量，通过握力、步行速度和短小进行评估 物理性能电池(由站立平衡、行走速度和椅子站立组成)。目标3：向内 在整个宇宙队列中，补充可可黄醇可减少骨折事件的发生，根据以下评估 年度问卷调查。我们将探索可可黄烷醇对骨折预后的影响是否是中介的。 通过跌倒和/或骨密度的变化。在探索性目标中，我们还将评估复合维生素对 这些结果都是一样的。RCTS测试复合维生素对跌倒和肌肉骨骼结果的影响 缺乏。这项辅助研究最大限度地提高了成本效益，填补了有关黄烷醇影响的知识空白。 用于初级预防跌倒。我们预计，拟议中的严格翻译研究将阐明 补充黄烷醇改善肌肉骨骼健康，预防摔倒和体能下降 美国越来越多的老年人具有潜在的临床和公共健康益处。

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.