Nutritional Intervention for Age-Related Muscular Function and Strength Losses

描述（由申请人提供）：肌肉减少症，定义为与年龄相关的肌肉质量、肌肉功能和力量损失，在老年人中非常普遍。肌肉减少症是美国快速增长的老龄化人口面临的最大公共卫生问题之一，并导致福尔斯、骨折和相关疾病的发病率增加。我们实验室以及许多其他实验室的先前观察已经证明了2-羟基-2-甲基丁酸盐（HMB）单独或与其他氨基酸组合在增强年轻运动员肌肉力量和功能方面的功效。我们最近已经证明，HMB与其他两种氨基酸（精氨酸和赖氨酸）的组合在一项为期一年的前瞻性研究中有效地增加了老年男性和女性的肌肉质量。在分析数据（初步结果）时，我们证明了该人群中25-OH维生素D3水平与肌肉力量改善水平之间的密切相关性。我们注意到，血浆25-OH维生素D3水平>30 ng/ml的个体表现出补充HMB和两种氨基酸的肌肉力量增加，而血浆25- OH维生素D3 <30 ng/ml的个体则没有。这些数据构成了我们目前假设的基础，即HMB和维生素D补充剂的组合将是协同的，并将导致整体肌肉力量，功能和肌肉质量的显著增强。我们提出这些I期和II期研究来证明我们的假设。I期研究将测试HMB和维生素D组合的短期（12周）疗效，以预防和逆转老年人肌肉减少症以及肌肉力量和功能的相关损失。我们计划招募100名男性和女性，他们将被分配到四种饮食治疗之一：（1）对照;（2）HMB（钙盐），3.0 g/天;（3）2，000 IU维生素D;和（4）HMB，3.0 g/天+2，000 IU维生素D。受试者将接受每周3天的锻炼计划，并将每隔四周测量身体成分和力量。我们希望在这项简短的研究中证明HMB和维生素D之间的协同作用。II期将测试HMB和维生素D的这种协同组合对增强老年人肌肉力量和功能的长期（12个月）疗效，从而改善生活质量。第二阶段将包括一个运动手臂就像第一阶段，但也将包括一个非运动手臂，因为许多老年人不参加锻炼计划。除了身体组成和功能和力量数据外，还将获得肌肉活检，并进行肌纤维和蛋白质组学分析。我们预计，所产生的数据将导致进一步的研究，研究老年人肌肉和肌肉功能丧失的机制。在为期一年的研究中，肌肉力量和肌肉功能的改善以及身体成分的改善将用于销售含有HMB和维生素D的产品。 公共卫生相关性：目前的估计将大部分美国老年人置于福尔斯的风险之中，并有潜在的发病率。这些福尔斯中的很大一部分与肌肉力量和功能下降直接相关。由于很大一部分老年人群存在维生素D缺乏的风险，因此纠正此类缺乏并专门针对肌肉力量、功能和质量的产品可能会显著改善健康状况，提高生活质量，特别是有助于降低这一人群中福尔斯和损伤的发生率。此外，根据所有年龄段普遍存在的维生素D缺乏症的发病率，我们预计年轻人口也将受益于类似的补充。

DESCRIPTION (provided by applicant): Sarcopenia, defined as age related loss of muscle mass and muscle function and strength, is very prevalent among the elderly. Sarcopenia is one of the largest public health problems facing a rapidly increasing, aging population in the United States and leads to increased incidence of falls, fractures and associated morbidities. Previous observations from our laboratory, as well as from many other laboratories, have demonstrated the efficacy of 2-hydroxy-2-methylbutyrate (HMB) alone or in combination with other amino acids in enhancing muscle strength and function in young athletes. We have recently demonstrated that the combination of HMB with two other amino acids, arginine and lysine, was effective in increasing muscle mass in elderly men and women during a year-long prospective study. When analyzing the data (Preliminary Results), we demonstrated a close correlation between the levels of 25-OH Vitamin D3 in this population and the level of improvement in muscle strength. We noted that individuals with plasma 25-OH Vitamin D3 levels >30 ng/ml manifested muscle strength gains supplemented with HMB and two amino acids, while those with plasma 25- OH Vitamin D3 of <30 ng/ml did not. These data form the basis of our current hypothesis that the combination of HMB and Vitamin D supplementation will be synergistic and will result in significant enhancements in overall muscle strength, function and muscle mass. We propose these Phase I and Phase II studies to prove our hypothesis. The Phase I study will test the short-term (12-wk) efficacy of a combination of HMB and Vitamin D to prevent and reverse muscle sarcopenia and the associated losses of muscular strength and functionality in older adults. We plan to recruit 100 men and women who will be assigned to one of four dietary treatments: (1) Control; (2) HMB (calcium salt), 3.0 g/day; (3) 2,000 IU Vitamin D; and (4) HMB, 3.0 g/d + 2,000 IU Vitamin D. The subjects will undergo a 3-day per week exercise program, and body composition and strength will be measured at four week intervals. We expect to demonstrate the synergy between HMB and Vitamin D in this short study. Phase II will test the long-term (12-mos) efficacy of this synergistic combination of HMB and Vitamin D on the enhancement of muscle strength and functionality in the elderly, thus leading to improved quality of life. Phase II will include an exercise arm just like Phase I, but will also include a non-exercise arm because many elderly adults do not participate in an exercise program. In addition to body composition and function and strength data, muscle biopsies will be obtained and muscle fiber and proteomic analysis will be performed. We anticipate that the data generated will lead to further research looking at mechanism(s) involved in loss of muscle and muscle function in the elderly. Improvement in muscle strength and muscle function as well as improvements in body composition over the year-long study will be used to market a product containing HMB and Vitamin D. PUBLIC HEALTH RELEVANCE: Current estimates place a large portion of the older U.S. populous at risk for falls with potential morbidities. A large percentage of these falls are directly related to decreased muscle strength and function. Since a significant portion of the older population is at risk of having a Vitamin D deficiency, a product that corrects such deficiencies and specifically targets muscle strength, function, and mass is likely to produce significant improvements in health, improve the quality of life, and in particular, help to decrease the incidence of falls and injury in this group. Moreover, based upon the incidence of widespread Vitamin D deficiency in all ages, we anticipate the younger population will also benefit from similar supplementation.