Adverse metabolic effects of dietary sugar _ Ad libitum vs energy-balanced diets

描述（由申请人提供）：最近的研究表明，与等热量的葡萄糖或低脂牛奶相比，食用高果糖玉米糖浆（HFCS）或蔗糖甜饮料会增加健康成年人CVD的脂质/脂蛋白风险因素。这些研究中时间最长的一项采用了6个月的干预，也显示肝脏和肌肉TG增加，内脏脂肪沉积增加。这些研究都没有发现摄入HFCS/蔗糖饮料的受试者与对照饮料相比体重增加的差异。这些结果表明，不仅仅是过量的卡路里和体重增加介导了膳食糖/果糖对代谢疾病发展的影响;相反，膳食糖本身也是一个贡献者。然而，目前尚不清楚在缺乏正能量平衡和体重增加的情况下，摄入过量的糖是否会增加代谢疾病的风险因素，也不清楚糖摄入的不良影响是否会因体重增加而加剧。这项研究将测试以下总体假设：即使在能量平衡的饮食中食用HFCs加糖饮料，也会增加代谢疾病的风险因素，从而防止体重增加，并且当在导致体重增加的正能量平衡环境中食用HFCs加糖饮料时，风险因素会在更大程度上增加。我们还将检验假设，即在设盲、受控的饮食条件下，食用含HFCs的饮料比食用含糖精的饮料更能增加能量摄入和体重增加。我们将在3组年轻健康成年人中测量与代谢疾病相关的风险因素和过程，这些成年人将消耗1）25%的能量需求作为HFCS-甜味饮料，采用能量平衡饮食; 2）25%的能量需求作为HFCS-甜味饮料，采用随意饮食;或3）甜菜碱-甜味饮料，采用随意饮食8周。在整个研究期间，将向受试者提供所有饮食，其配制为在所有3个实验组中实现相当的大量营养素摄入量（55%能量为碳水化合物，35%脂肪，15%蛋白质）。我们假设，尽管没有体重增加，但在能量平衡的饮食中饮用HFCs加糖饮料将导致不良的代谢影响。与含HFCs的饮料相比，在随意饮食的情况下饮用含HFCs的饮料将导致能量摄入增加和体重增加，并且还将导致比在能量平衡饮食的情况下饮用含HFCs的饮料更显著的不良代谢影响。这些结果将表明，食用含HFCs的饮料会直接增加代谢疾病的风险，这是通过果糖对脂质和碳水化合物代谢的不利影响实现的，也会间接增加代谢疾病的风险，这是通过含HFCs的饮料促进过量能量摄入和体重增加实现的。这些发现将有可能影响饮食指南和公共卫生政策。

DESCRIPTION (provided by applicant): Recent studies have demonstrated that consuming high fructose corn syrup (HFCS)- or sucrose-sweetened beverages increased lipid/lipoprotein risk factors for CVD in healthy adults compared with iso-caloric amounts of glucose or low-fat milk. The longest of these studies, which utilized a 6-month intervention, also showed increased liver and muscle TG and increased visceral adipose deposition. Neither of these studies found differences in weight gain between subjects consuming HFCS/sucrose beverages compared with control beverages. These results suggest that it is not just excess calories and weight gain that mediate the effects of dietary sugar/fructose on the development of metabolic disease; rather, dietary sugar per se is also a contributor. However, it is not known whether consumption of excessive amounts of sugar can increase risk factors for metabolic disease in the absence of positive energy balance and weight gain, nor whether the adverse effects of sugar consumption are exacerbated by weight gain. This study will test the overall hypotheses that consumption of HFCS-sweetened beverages increases risk factors for metabolic disease even when consumed with an energy-balanced diet that prevents weight gain, and that risk factors are increased to a greater extent when HFCS-sweetened beverages are consumed in a setting of positive energy balance that results in weight gain. We will also test the hypothesis, that under blinded, controlled, dietary conditions, consumption of HFCS-sweetened beverages will increase energy intake and body weight gain more than consumption of aspartame-sweetened beverages. We will measure risk factors and processes associated with metabolic disease in 3 groups of young, healthy adults who will consume 1) 25% of energy requirement as HFCS-sweetened beverages with an energy-balanced diet; 2) 25% of energy requirement as HFCS- sweetened beverages with an ad libitum diet; or 3) aspartame-sweetened beverages with an ad libitum diet for 8 weeks. All diets, formulated to achieve a comparable macronutrient intake (55% energy as carbohydrate, 35% fat, 15% protein) among all 3 experimental groups, will be provided to the subjects throughout the entire study. We hypothesize that consumption of HFCS-sweetened beverages with the energy-balanced diet will result in adverse metabolic effects, despite the absence of weight gain. Consumption of HFCS-sweetened beverages with the ad libitum diet will result in increased energy intake and body weight gain compared with aspartame-sweetened beverages, and will also result in adverse metabolic effects that are more marked than with consumption of HFCS-sweetened beverages with the energy-balanced diet. These results will demonstrate that consumption of HFCS-sweetened beverages increases risk for metabolic disease both directly, via the adverse effects of fructose on lipid and carbohydrate metabolism, and indirectly, via the effects of HFCS-sweetened beverages to promote excess energy intake and body weight gain. These findings will have the potential to influence dietary guidelines and public health policy.