BODY PROTEIN METABOLISM AND NUTRITION IN AIDS-WASTING

体重下降，尤其是瘦体质量，是HIV感染的主要表现。瘦体质量（LBM）的丧失是艾滋病患者消瘦综合征的最早表现。科学证据还表明，很大比例的死亡与营养不良和消瘦有关。我们最近证明，结合使用两种氨基酸（精氨酸和谷氨酰胺）和亮氨酸的代谢物- β -羟基- β -甲基丁酸酯（HMB）进行有针对性的营养干预，在促进瘦体重、增加肌肉质量和功能以及改善免疫功能的一些基本参数方面具有显著的积极作用。拟议的研究旨在确定这种氨基酸营养混合物增加艾滋病患者瘦体重和逆转消瘦综合征的机制。10名在前一年体重减轻10%或以上的艾滋病患者将被招募参加这项研究。在患者的饮食中添加含有HMB、精氨酸和谷氨酰胺的营养混合物，持续8周。利用稳定同位素技术，在补充8周前后评估全身蛋白质周转、肌肉蛋白质合成和分解率。我们假设HMB/精氨酸/谷氨酰胺组合将导致蛋白质合成增加和蛋白质水解减少，从而显著逆转这些患者的消瘦综合征，最终提高寿命和生活质量。建议的商业应用：这种营养组合已被证明可以增强消瘦的艾滋病患者的免疫功能和瘦体重。这种组合将有可能在各种产品中销售。很高比例的艾滋病患者会出现与该疾病相关的意外体重减轻，从而导致该营养产品的巨大市场潜力。最初的产品在即饮配方中含有营养素组合。一种含有高质量蛋白质和其他营养素的均衡营养产品可能会随之而来。这些产品将在市场上脱颖而出，因为它们将基于强有力的临床数据。

Weight loss, especially lean body mass, is a major manifestation of HIV infection. Loss of lean body mass (LBM) is the earliest manifestation of the wasting syndrome seen in AIDS patients. Scientific evidence also suggests that a high percentage of deaths is related to malnutrition and wasting. We have recently demonstrated that targeted nutritional intervention using a combination of two amino acids (arginine and glutamine) and a metabolite of leucine, beta-hydroxy-beta-methyl-butyrate (HMB), had marked positive effects in promoting lean body mass, increasing muscle mass and function and improving some essential parameters of immune functions. the proposed study is designed to determine the mechanism(s) by which this amino acid nutrient mixture increased lean body mass and reversed the wasting syndrome in AIDS patients. Ten patients with AIDS who have demonstrated weight loss of 10% or greater in the previous year will be recruited for the study. Patients's diets will be supplemented with the nutrient mixture containing HMB, arginine, and glutamine for 8 weeks. Using stable isotope techniques, whole body protein turnover and muscle protein synthesis and breakdown rates will be assessed prior to and after 8 weeks of supplementation. We hypothesize that the HMB/arginine/glutamine combination will result in an increase in protein synthesis and a decrease in proteolysis leading to a significant reversal in the wasting syndrome seen in these patients, ultimately leading improved longevity and quality of life. PROPOSED COMMERCIAL APPLICATION: This nutritional combination has been shown to enhance immune function and lean mass in wasting AIDS patients. It will be possible to market this combination in a variety of products. A high percent of patients with AIDS will have unintentional weight loss associated with the disease, resulting in a large market potential for the nutritional product. The initial product contains the nutrient combination in a ready-to-drink formulation. A balanced nutritional product containing high quality protein and other nutrients would likely follow. The products will distinguish themselves in the market because they will be based on strong clinical data.