Nutritional Intervention for Age-Related Muscular Function and Strength Losses

针对与年龄相关的肌肉功能和力量损失的营养干预

• 批准号: 7909359
• 负责人: John A Rathmacher
• 金额: $ 10万
• 依托单位: METABOLIC TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7909359
• 关键词: Adult; Affect; Age; American; Amino Acids; Arthritis; Back; Biochemical; Biopsy; Body Composition; Bone Density; Bone callus; Bone remodeling; Bunion; Calcium; Caliber; Censuses; Centers for Disease Control and Prevention (U.S.); Cholecalciferol; Climate; Communicable Diseases; Data; Data Analyses; Deformity; Dietary Intervention; Disease; Economics; Effectiveness; Elderly; Elderly man; Elderly woman; Equilibrium; Exercise; Experimental Designs; Fall prevention; Fast-Twitch Muscle Fibers; Fiber; Flexor; Fracture; Functional disorder; Future; Gait; General Population; Health; Incidence; Individual; Injury; Investigation; Joint Instability; Knee; Knowledge; Laboratories; Labyrinth; Lead; Legal patent; Life; Literature; Longitudinal Studies; Marketing; Measurement; Measures; Metabolic; Morbidity - disease rate; Muscle; Muscle Fibers; Muscle function; Musculoskeletal; Nutrient; Older Population; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Planet Mars; Plasma; Pneumonia; Population; Probability; Prospective Studies; Proteomics; Public Health; Publishing; Quality of life; Recruitment Activity; Relative (related person); Reporting; Research; Risk; Risk Factors; Screening procedure; Somatotype; Structure of nail of toe; Sum; Supplementation; Techniques; Testing; Time; Time Study; Toes; Training; Translating; United States; Vision; Vitamin D; Vitamin D Deficiency; Vitamin D2; Vitamins; Woman; age related; aging population; arginyllysine; arm; base; bone; bone turnover; clinically significant; combat; economic cost; fall risk; falls; foot; grasp; improved; men; metabolic abnormality assessment; muscle aging; muscle form; muscle metabolism; muscle strength; phase 1 study; phase 2 study; prevent; programs; prospective; protein degradation; public health relevance; sarcopenia; sports related nutrition; wasting

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.

描述（由申请人提供）：肌少症，定义为与年龄相关的肌肉质量、肌肉功能和力量的损失，在老年人中非常普遍。骨骼肌减少症是美国快速增长的老龄化人口面临的最大的公共卫生问题之一，导致跌倒、骨折和相关疾病的发生率增加。我们实验室以及许多其他实验室先前的观察已经证明，2-羟基-2-甲基丁酸酯（HMB）单独使用或与其他氨基酸联合使用在增强年轻运动员肌肉力量和功能方面的功效。在一项为期一年的前瞻性研究中，我们最近证明了HMB与另外两种氨基酸（精氨酸和赖氨酸）的结合对增加老年男性和女性的肌肉质量有效。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。我们注意到，血浆中25-OH维生素D3水平为bbb30 ng/ml的个体在补充HMB和两种氨基酸后，肌肉力量增加，而血浆中25-OH维生素D3水平<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着增强。我们提出这些第一阶段和第二阶段的研究来证明我们的假设。I期研究将测试HMB和维生素D联合预防和逆转老年人肌肉减少症和相关肌肉力量和功能损失的短期（12周）疗效。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中的一种：(1)控制；(2) HMB（钙盐），3.0 g/d；(3) 2000 IU维生素D；(4) HMB， 3.0 g/d + 2000 IU维生素d。受试者将进行每周3天的锻炼计划，每四周测量一次身体成分和力量。我们希望在这个简短的研究中证明HMB和维生素D之间的协同作用。II期将测试HMB和维生素D协同组合在增强老年人肌肉力量和功能方面的长期（12个月）疗效，从而提高生活质量。第二阶段将像第一阶段一样包括一个锻炼臂，但也将包括一个非锻炼臂，因为许多老年人不参加锻炼项目。除了身体成分、功能和力量数据外，还将获得肌肉活检，并进行肌肉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，着眼于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。