Phosphorus-based Food Additives, Mineral Metabolism and Cardiovascular Health

磷基食品添加剂、矿物质代谢和心血管健康

• 批准号: 8280976
• 负责人: Orlando M Gutierrez
• 金额: $ 18.31万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-20 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8280976
• 关键词: Address; Adverse effects; Alabama; American; Animals; Appearance; Biological Markers; Blood; Blood Vessels; Bone Diseases; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cause of Death; Cessation of life; Chronic Kidney Failure; Clinical Research; Communities; Consumption; Data; Diet; Dietary Factors; Dietary Intervention; Dietary Phosphorus; Dilatation - action; Disease; Event; Food; Food Additives; Food Processing; Food Supply; Future; General Population; Health; Home environment; Hormones; Human; Individual; Industry; Inflammation; Intake; Kidney Diseases; Knowledge; Life; Link; Mediating; Metabolic; Metabolism; Minerals; Oral; Outcome; Outcome Study; Participant; Pathogenesis; Persons; Phosphorus; Phosphorus Metabolism Disorders; Physiological; Play; Population; Process; Public Health; Recommendation; Risk Factors; Role; Salts; Taste Perception; Testing; Time; Translational Research; United States Food and Drug Administration; Universities; Urine; Visit; base; brachial artery; design; fast food; feeding; fibroblast growth factor 23; food consumption; healthy volunteer; high risk; inorganic phosphate; modifiable risk; phosphorus metabolism; public health relevance; response; trend; vascular inflammation

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. PUBLIC HEALTH RELEVANCE: Cardiovascular diseases (CVD) remain the major cause of death in the US. Disturbances in phosphorus metabolism are strongly linked to CVD, and thus, may be modifiable targets of therapy. The proposed studies will examine the role of excess phosphorus-based food additive intake in the pathogenesis of disordered phosphorus metabolism in healthy volunteers, which will help clarify the potential public health implications of the nearly ubiquitous distribution of phosphorus-based food additives in the US food supply

描述(由申请人提供)：越来越多的证据表明，磷代谢紊乱导致过度的心血管疾病事件和死亡，独立于既定的危险因素。过量的膳食磷摄入量在这些疾病的发病机制中起着核心作用。在美国，膳食中的磷摄入量远远超过目前推荐的每日摄入量，这在很大程度上是由于美国食品供应中几乎无处不在的含磷食品添加剂的分布。这些添加剂被食品制造业大量使用，以改善加工食品的味道、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日常磷摄入量。虽然目前美国食品和药物管理局认为公众食用是安全的，但最近 数据表明，大量摄入这些添加剂可能会对健康产生重要影响。在动物和人体研究中，高磷添加剂的摄入损害了心血管健康。此外，更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(FGF23)，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一个重要的、潜在的可改变的危险因素。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量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关注点。具体地说，我们将(1)确定添加剂强化食品对血磷和FGF23水平的影响，以及炎症的生物标志物，以及(2)确定添加剂强化食品对健康人群血管反应性的影响。 志愿者。参与者将在为期4周的时间内食用由阿拉巴马大学临床研究单位代谢厨房准备的标准化饮食。将在饮食干预期间收集血液和尿液参数，以评估研究结果变量。此外，还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研究的设计和实施提供关键的先导数据，该研究旨在检查调制磷食品添加剂对各种肾脏疾病的矿物质代谢和心血管健康的影响。 公共卫生相关性：心血管疾病(CVD)仍然是美国的主要死亡原因。磷代谢紊乱与心血管疾病密切相关，因此，可能是可改变的治疗靶点。这项拟议的研究将考察过量的磷食品添加剂摄入量在健康志愿者磷代谢紊乱的发病机制中的作用，这将有助于澄清美国食品供应中几乎无处不在的磷食品添加剂分布对公众健康的潜在影响