Dietary carbohydrate & glycemic index effects on oxidation & inflammation

描述（由申请人提供）： 传统的CVD危险因素和动脉粥样硬化风险之间的直接关系已经得到了很好的建立。降低血压和血脂的饮食调整为风险降低提供了可能的解释。然而，氧化应激，包括LDL-c（oxLDL）的氧化，似乎是动脉粥样硬化发病机制中重要的（如果不是强制性的）步骤，并且可能加速这一以炎症为特征的过程（Steinberg，1989）。使用血清和尿液生物标志物测量炎症和氧化应激可以提供对CVD风险降低机制的深入了解，而不仅仅是通过脂质或其他CVD风险因素预测。 在本申请中，我们提出测量改变饮食中碳水化合物的类型（高和低血糖指数）和量（高碳水化合物和低碳水化合物）的饮食模式对炎症和氧化应激标志物的影响。本研究将在OMNI-CARB试验（最佳宏量营养素摄入量和碳水化合物）的背景下进行-这是一项随机交叉试验，2008年至2011年期间在约翰霍普金斯和哈佛招募了160名高血压前期或1期高血压成人参与者。申请人是合作研究者，本申请得到了主要研究者（Frank Sacks，哈佛大学）的全力支持和批准。OMNI-CARB研究的主要目的是解决将碳水化合物从高水平（58% kcal）降低到低水平（43% kcal）和将血糖指数从高水平（血糖指数>85）降低到低水平（血糖指数<55）对主要的饮食相关CVD风险因素以及胰岛素敏感性的单独和组合的功效。在本试验中，反映氧化应激和炎症的生物标志物的测量是特别相关的结果，因为在固定的常量营养素饮食（碳水化合物，蛋白质和脂肪保持不变）中改变血糖指数预计仅对血脂和其他传统CVD风险因素（血压）产生适度影响。我们假设，消费一个固定的“低碳水化合物饮食”和“低血糖指数”饮食将减少氧化应激和炎症相比，消费等热量的“高碳水化合物”饮食和“高血糖指数”饮食。 公共卫生相关性：在本申请中，我们提出测量改变饮食中碳水化合物的类型（高和低血糖指数）和量（高碳水化合物和低碳水化合物）的饮食模式对炎症和氧化应激标志物的影响。本研究将在OMNI-CARB试验（最佳宏量营养素摄入量和碳水化合物）的背景下进行-这是一项随机交叉试验，2008年至2011年期间在约翰霍普金斯和哈佛招募了160名高血压前期或1期高血压成人参与者。我们假设，消费一个固定的“低碳水化合物饮食”和“低血糖指数”饮食将减少氧化应激和炎症相比，消费等热量的“高碳水化合物”饮食和“高血糖指数”饮食。 (End摘要）

DESCRIPTION (provided by applicant): The direct relationship between traditional CVD risk factors and risk of atherosclerosis is well established. Dietary modifications which lower blood pressure and lipids provide a likely explanation for much of the risk reduction. However, oxidative stress, including oxidation of LDL-c (oxLDL) appears to be an important, if not obligatory step in the pathogenesis of atherosclerosis and may accelerate this process which is marked by inflamation (Steinberg, 1989). Measurement of inflammation and oxidative stress using serum and urine biomarkers may offer insight into mechanisms of CVD risk reduction beyond that which is predicted by lipids or other CVD risk factors alone. In this application we propose to measure the effects of dietary patterns that vary the type (high and low glycemic index) and the amount of carbohydrate in the diet (high carbohydrate and low carbohydrate) on markers of inflammation and oxidative stress. This study will be conducted within the setting of the OMNI-CARB trial (Optimal Macronutrient Intake and Carbohydrates)- a randomized cross over trial of 160 adults with prehypertension or stage 1 hypertension enrolling participants between 2008 and 2011 at Johns Hopkins and Harvard. The applicant is a co-investigator and this application has the full support and approval of the Principal Investigator (Frank Sacks, Harvard University). The primary aim of the OMNI-CARB study is to address the efficacy, separate and combined, of reducing carbohydrate from a high level (58% kcal) to a low level (43% kcal) and of lowering the glycemic index from a high level (glycemic index>85) to a low level (glycemic index<55) on the major established diet-related CVD risk factors, as well as insulin sensitivity. Measurement of biomarkers reflective of oxidative stress and inflammation are particularly relevant outcomes in this trial since modifying the glycemic index within a fixed macronutrients diet (carbohydrate, protein and fats held constant) is expected to results in only modest effects on serum lipids and other traditional CVD risk factors (blood pressure). We hypothesize that consumption of a fixed "low carbohydrate diet" and "low glycemic index" diet will decrease oxidative stress and inflammation compared with consumption an isocaloric "high carbohydrate" diet and "high glycemic index" diet. PUBLIC HEALTH RELEVANCE: In this application we propose to measure the effects of dietary patterns that vary the type (high and low glycemic index) and the amount of carbohydrate in the diet (high carbohydrate and low carbohydrate) on markers of inflammation and oxidative stress. This study will be conducted within the setting of the OMNI-CARB trial (Optimal Macronutrient Intake and Carbohydrates)- a randomized cross over trial of 160 adults with prehypertension or stage 1 hypertension enrolling participants between 2008 and 2011 at Johns Hopkins and Harvard. We hypothesize that consumption of a fixed "low carbohydrate diet" and "low glycemic index" diet will decrease oxidative stress and inflammation compared with consumption an isocaloric "high carbohydrate" diet and "high glycemic index" diet. (End of Abstract)