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

描述（由申请人提供）：大量观察和实验研究表明，心血管系统中的炎症氧化环境可导致内皮病理变化并促成动脉粥样硬化。抗氧化营养素被认为可能有助于减少内皮功能障碍和减少心血管事件的发生率。然而，以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。尽管最近的试验结果无效，但抗氧化剂的潜在益处的生物可接受性仍然很强。需要继续努力，以确定具体的抗氧化剂是有效的治疗剂。目的：这项研究将确定含有谷胱甘肽的膳食补充剂是否会降低炎症标志物的水平，以及补充精氨酸的存在与否是否会增加谷胱甘肽治疗的有效性。设计：随机、双盲、安慰剂对照、平行组、可行性研究。将90名代谢综合征成人随机分配至以下组，持续8周：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）。将在基线、第2、4和8周收集数据。主要研究结果是炎症的血清标志物，包括单核细胞趋化蛋白-1（MCP-1）、白细胞介素6（IL-6）、肿瘤坏死因子-α（TNF-1）和可溶性细胞间粘附分子-1（sICAM-1）。次要结果包括血压、血胆固醇、空腹胰岛素、血清异前列腺素（氧化应激的测量）和s-亚硝基谷胱甘肽（一种稳定的含一氧化氮的化合物）。含义：如果谷胱甘肽，+/-精氨酸，可以有效地降低炎症标志物，这将表明一个安全和相对便宜的治疗，以减少心血管疾病的风险。最近的研究表明，氧化应激和与之相关的炎症在普通人群中非常常见，因此在这一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：本研究的主要目的是检查抗氧化剂膳食补充剂（谷胱甘肽）与或不与氨基酸膳食补充剂（精氨酸）对心血管疾病风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组合可以成功地降低这些炎症性血液标志物的水平，这将表明可能的心血管疾病预防治疗，这将是相对安全和廉价的，并广泛适用于公众。

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.