Effects of GSH +/- Arginine on Markers of Inflammation Among Adults with CVD Risk

GSH /-精氨酸对有 CVD 风险的成年人炎症标志物的影响

• 批准号: 7739875
• 负责人: CHRISTOPHER D GARDNER
• 金额: $ 31.4万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7739875
• 关键词: Adherence; Adult; Adverse effects; Amino Acids; Antioxidants; Area; Arginine; Atherosclerosis; Beta Carotene; Biological; Blood; Blood Pressure; Blood Vessels; Cardiovascular system; Cell Adhesion; Characteristics; Cholesterol; Clinical Trials; Data; Double-Blind Method; Effectiveness; Endothelium; Environment; Epidemic; Event; Evolution; Fasting; Feasibility Studies; Functional disorder; Future; General Population; Glutathione; Half-Life; Health; Incidence; Individual; Inflammation; Inflammatory; Inflammatory Response; Injury; Insulin; Insulin Resistance; Intercellular adhesion molecule 1; Interleukin-6; Intervention; Intravenous infusion procedures; Investigation; Isoprostanes; Lead; Liposomes; Measures; Metabolic; Metabolic syndrome; Metabolism; Monitor; Monocyte Chemoattractant Protein-1; Nitric Oxide; Nutrient; Oral; Outcome Assessment; Outcome Measure; Outcome Study; Oxidative Stress; Participant; Pathologic; Physiological; Placebo Control; Placebos; Population Study; Preventive; Process; Protocols documentation; Randomized; Reduced Glutathione; Reproducibility; Research; Research Design; Risk; Risk Factors; Role; Serum; Serum Markers; Source; Supplementation; Therapeutic Agents; Treatment Protocols; Tumor Necrosis Factor-alpha; United States National Institutes of Health; Upper arm; Vascular Diseases; Vasodilation; Vitamin E; Work; cardiovascular disorder risk; cardiovascular disorder therapy; control trial; cytokine; design; dietary supplements; follow-up; inflammatory marker; innovation; interest; meetings; novel; nutrition; public health priorities; public health relevance; research study; response; secondary outcome; vascular inflammation

DESCRIPTION (provided by applicant): A number of observational and experimental studies have shown that an inflammatory oxidative environment in the cardiovascular system can lead to pathologic changes in the endothelium and contribute to atherosclerosis. Antioxidant nutrients are presumed likely to contribute to a decrease of endothelial dysfunction and to diminish the incidence of cardiovascular events. However, the previous use of antioxidant supplements in clinical trials (e.g., Vitamins E and C, beta-carotene) has yielded disappointing and controversial results. Despite the null findings from recent trials, the biological plausibility of potential benefits from antioxidants remains strong. Continued work is needed in trying to identify specific antioxidants that are effective therapeutic agents. OBJECTIVE: This study will determine whether a dietary supplement containing glutathione will lower levels of inflammatory markers, and whether the presence or absence of supplemental arginine will add to the effectiveness of the glutathione therapy. DESIGN: This is a randomized, double-blind, placebo-controlled, parallel-arm, feasibility study. Ninety adults with Metabolic Syndrome will be randomly assigned for 8 weeks to either: 1) glutathione (GSH, n=30), 2) glutathione + arginine (GSH+Arg, n=30) or placebo (Plac, n=30). Data will be collected at baseline, 2, 4, and 8 weeks. Primary study outcomes are serum markers of inflammation including monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-1) and soluble intercellular adhesion molecule-1 (sICAM-1). Secondary outcomes include blood pressure, blood cholesterol, fasting insulin, serum isoprostanes (a measure of oxidative stress) and s-nitrosyl glutathione (a stable, nitric oxide containing compound). IMPLICATIONS: If glutathione, +/- arginine, can effectively lower inflammatory markers, this would suggest a safe and relatively inexpensive therapy to reduce the risk of cardiovascular disease. Recent studies have shown that oxidative stress and the inflammation associated with it are very common in the general population, and so any beneficial therapies found in this area would have widespread benefits. PUBLIC HEALTH RELEVANCE: The major purpose of this study is to examine the effects of an antioxidant dietary supplement (glutathione) with or without an amino acid dietary supplement (arginine) on markers of inflammation among adults with elevated cardiovascular disease risk factors. If the glutathione, or its combination with arginine, can successfully decrease the levels of these inflammatory blood markers, this would suggest a possible preventive therapy for cardiovascular disease that would be relatively safe and inexpensive with widespread availability for the general public.

描述（由申请人提供）：许多观察性和实验研究表明，心血管系统中的炎症性氧化环境可导致内皮的病理变化，并导致动脉粥样硬化。假定抗氧化剂的营养可能导致内皮功能障碍降低并减少心血管事件的发生率。但是，先前在临床试验中使用抗氧化剂补充剂（例如，维生素E和C，β-胡萝卜素）产生了令人失望和有争议的结果。尽管最近的试验发现了无效的发现，但抗氧化剂潜在益处的生物学合理性仍然很强。尝试确定有效治疗剂的特定抗氧化剂需要继续工作。目的：这项研究将确定含有谷胱甘肽的饮食补充剂是否会降低炎症标志物的水平，以及是否存在或不存在补充精氨酸会增加谷胱甘肽治疗的有效性。设计：这是一项随机，双盲，安慰剂对照，并行臂，可行性研究。患有代谢综合征的90名成年人将被随机分配8周，要么：1）谷胱甘肽（GSH，n = 30），2）谷胱甘肽 +精氨酸（GSH + ARG，n = 30）或安慰剂（Plac，n = 30）。数据将在基线，2、4和8周时收集。主要的研究结果是炎症的血清标志物，包括单核细胞化学吸引蛋白1（MCP-1），白介素6（IL-6），肿瘤坏死因子 - α（TNF-1）和可溶性细胞间粘附分子分子1（SICAM-1）。次要结局包括血压，血液胆固醇，空腹胰岛素，血清异丙烷（氧化应激的量度）和S-硝基基谷胱甘肽（一种稳定的，含有一氧化氮的化合物）。含义：如果谷胱甘肽+/-精氨酸可以有效地降低炎症标记，这将表明一种安全且相对便宜的疗法以降低心血管疾病的风险。最近的研究表明，氧化应激及其相关的炎症在一般人群中非常普遍，因此在该领域发现的任何有益疗法都将具有广泛的益处。 公共卫生相关性：这项研究的主要目的是检查具有或没有氨基酸饮食补充剂（精氨酸）抗氧化剂饮食补充剂（谷胱甘肽）对心血管疾病危险因素升高的成年人炎症标志物的影响。如果谷胱甘肽或其与精氨酸的结合可以成功降低这些炎性血液标记的水平，这将表明对心血管疾病的预防疗法可能会相对安全且廉价，并且对普通公众的可用性广泛。