Phosphorus-based Food Additives, Mineral Metabolism and Cardiovascular Health

描述（由申请方提供）：越来越多的证据表明，磷代谢紊乱导致过多的心血管疾病事件和死亡，与已确定的风险因素无关。过量的膳食磷摄入在这些疾病的发病机制中起着核心作用。在美国，膳食磷的消耗量远远超过目前的每日建议摄入量，这在很大程度上是由于美国食品供应中几乎无处不在的磷基食品添加剂。这些添加剂被食品制造业大量使用，以提高加工食品的味道、外观和保质期，因此可以显著增加食用美国饮食中典型的方便和快餐食品的人的每日磷摄入量。虽然美国食品和药物管理局目前认为公众消费是安全的，但最近 数据显示，大量摄入这些添加剂可能会对健康产生重大影响。在动物和人类研究中，高摄入磷添加剂损害心血管健康。此外，较高的磷摄入量刺激磷调节激素的分泌，如成纤维细胞生长因子23（FGF 23），其水平升高与炎症，心血管疾病事件和死亡有关。这些数据表明，过量摄入磷基食品添加剂是数百万消费典型美国饮食的人中磷代谢紊乱，炎症和心血管疾病的重要和潜在可改变的风险因素。然而，很少有生理学研究专门研究过量的商业磷添加剂摄入对健康志愿者磷酸盐代谢和心血管功能的影响。这是本应用程序的中心焦点。具体来说，我们将（1）确定添加剂增强的食物对血磷酸盐和FGF 23水平的影响，以及炎症的生物标志物，（2）确定添加剂增强的食物对健康人血管反应性的影响。 志愿者参与者将在4周的时间内食用由亚拉巴马大学临床研究单位代谢厨房准备的标准化饮食。将在整个饮食干预期间收集血液和尿液参数，以评估研究结局变量。此外，将在饮食干预前后评估肱动脉血流介导的扩张，以确定磷添加剂对血管功能的影响。这些结果将为未来干预性研究的设计和实施提供关键的试点数据，这些研究旨在研究调节磷基食品添加剂对肾脏疾病谱中矿物质代谢和心血管健康的影响。

DESCRIPTION (provided by applicant): Mounting evidence suggests that disturbances in phosphorus metabolism contribute to excess cardiovascular disease events and death independently of established risk factors. Excess dietary phosphorus intake plays a central role in the pathogenesis of these disorders. In the US, dietary phosphorus consumption far exceeds current recommendations for daily intake, in large part due to the nearly ubiquitous distribution of phosphorus-based food additives in the US food supply. These additives are heavily utilized by the food manufacturing industry to enhance the taste, appearance, and shelf-life of processed foods and thus, can substantially augment daily phosphorus intake in persons consuming convenience and fast foods typical of the American diet. While currently considered safe for public consumption by the US Food and Drug administration, recent data suggest that high intake of these additives may have important health consequences. High intake of phosphorus additives impaired cardiovascular health in animal and human studies. In addition, higher phosphorus intake stimulates the secretion of phosphorus-regulatory hormones such as fibroblast growth factor 23 (FGF23), elevated levels of which were associated with inflammation, cardiovascular disease events and death. These data suggest that excess intake of phosphorus-based food additives is an important and potentially modifiable risk factor for disturbed phosphorus metabolism, inflammation, and cardiovascular disease among millions of individuals consuming typical American diets. However, few physiological studies specifically examined the effect of excess commercial phosphorus additive intake on phosphate metabolism and cardiovascular function in healthy volunteers. This is the central focus of this application. Specifically, we will (1) determine the effect of additive-enhanced foods on blood phosphate and FGF23 levels, and biomarkers of inflammation, and (2) determine the effect of additive-enhanced foods on vascular reactivity in healthy volunteers. Participants will consume standardized diets prepared by the metabolic kitchen of the University of Alabama Clinical Research Unit over a 4-week period of time. Blood and urine parameters will be collected throughout the dietary intervention periods to assess study outcome variables. In addition, brachial artery flow mediated dilatation will be assessed before and after the dietary interventions to determine the effects of phosphorus additives on vascular function. These results will provide critical pilot data for the design and implementation of futur interventional studies aimed at examining the impact of modulating phosphorus-based food additives on mineral metabolism and cardiovascular health across the spectrum of kidney disease.