Effect of Antioxidants on Inflammatory Markers and FMVD

描述(申请人提供)：背景：许多观察和实验研究表明，公认的动脉粥样硬化的危险因素促进了血管系统的炎性氧化环境，这有利于内皮的病理变化。现在有大量证据表明，内皮功能障碍是动脉粥样硬化的先兆，也是加速动脉粥样硬化的因素。因此，抗氧化性营养素，包括维生素C、类胡萝卜素、生育酚和硒，可能有助于减少内皮功能障碍和减少心血管事件的发生。然而，以前在临床试验中使用抗氧化剂补充剂的结果令人失望和有争议。尽管试验结果无效，但在美国，饮食中抗氧化剂维生素的使用仍在继续增长。目的：在这项修订的应用中，我们的目标是确定天然富含抗氧化剂的食物与补充药丸抗氧化剂在一般健康的动脉粥样硬化风险受试者中对炎症和内皮功能标志物的短期疗效。设计：这是一项随机、单盲(饮食)/双盲(补充剂)、平行的可行性研究。90名有动脉粥样硬化和心脏病高危因素的成年人将被随机分配到以下两组：1)继续他们通常的饮食并服用安慰剂药片(n=30通常/plac)，2)继续他们通常的饮食并服用抗氧化剂补充药片(n=30通常/Supp)，或3)增加他们的抗氧化剂丰富的食物的摄入量，与补充剂药丸中的抗氧化剂含量密切匹配(n=30抗氧化剂-食品)，持续八周。数据将在基线、4周和8周收集。主要研究结果是炎症标志物，包括C-反应蛋白、纤维蛋白原、IL-6、肿瘤坏死因子-α和可溶性ICAM-1。次要结果包括血流介导的肱动脉扩张和尿异前列腺素。这项研究旨在评估动脉粥样硬化的新标记物对抗氧化剂干预的反应性。炎症标志物和内皮功能的测试可能提供一种快速可靠的方法，以低成本评估抗氧化剂干预的临床结果，并为未来更长期和更大规模的研究微调抗氧化剂的最佳组合、来源和剂量。

DESCRIPTION (provided by applicant): BACKGROUND: A number of observational and experimental studies have shown that the recognized risk factors for atherosclerosis promote an inflammatory oxidative environment in the vasculature that is conducive to pathologic changes in the endothelium. Considerable evidence now exists that endothelial dysfunction both precedes and accelerates atherosclerosis. Antioxidant nutrients, including vitamin C, carotenoids, tocopherols and selenium, may therefore be 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 has yielded disappointing and controversial results. Despite the null trial findings, the use of dietary antioxidant vitamins continues to grow in the U.S. OBJECTIVE: In this revised application, our objective is to determine the short-term efficacy of foods naturally rich in antioxidants vs. supplemental pill antioxidants on markers of inflammation and endothelial function in generally healthy subjects at risk of atherosclerosis. DESIGN: This is a randomized, single-blind (diets)/double blind (supplements), parallel, feasibility study. Ninety adults with elevated risk factors for atherosclerosis and heart disease will be randomly assigned to either: 1) continue their usual diet and receive placebo pills (n=30 Usual/Plac), 2) continue their usual diet and receive antioxidant supplement pills (n=30 Usual/Supp), or 3) increase their consumption of antioxidant rich foods closely matched to antioxidant content of the supplement pills (n=30 Antiox-Food) for eight weeks. Data will be collected at baseline, four, and eight weeks. Primary study outcomes are markers of inflammation including c-reactive protein, fibrinogen, IL-6, TNF-alpha and soluble ICAM-1. Secondary outcomes include flow mediated vasodilation of the brachial artery and urinary isoprostanes. IMPLICATIONS: This study is designed to evaluate the responsiveness of novel markers of atherosclerosis to antioxidant interventions. Tests of inflammatory markers and endothelial function may provide a rapid and reliable methodology to assess the clinical outcome of antioxidant interventions at low cost and allow for fine tuning the choice of optimal combinations, sources and doses of antioxidants for future longer term and larger scale studies.