Sodium Regulation in Individuals on Known Dietary Sodium Intake

已知膳食钠摄入量的个体的钠调节

• 批准号: 10004148
• 负责人: Cheryl Ann Marie Anderson
• 金额: $ 67.03万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10004148
• 关键词: Adolescent; Adult; Affect; Aldosterone; Ancillary Study; Animals; Area; Biological Markers; Blood; Blood Pressure; Bone Tissue; Cardiovascular Diseases; Clinical; Clinical Trials Design; Consumption; Cortisone; Data; Demographic Factors; Deposition; Diet; Dietary Potassium; Dietary Practices; Dietary Sodium; Doctor of Philosophy; Education; Energy Metabolism; Enrollment; Equilibrium; Excretory function; Feces; Funding; Glucocorticoids; Grant; Guidelines; Hormones; Hour; Hydrocortisone; Hypertension; Individual; Industry; Infrastructure; Intake; Kidney; Life; Measurement; Measures; Mediating; Metabolism; Mineralocorticoids; Minerals; Muscle; National Heart, Lung, and Blood Institute; Nonprofit Organizations; Outcome; Outcome Measure; Pattern; Population; Potassium; Potato; Prevalence; Principal Investigator; Process; Production; Public Health; Publishing; Randomized Clinical Trials; Randomized Controlled Trials; Regulation; Reporting; Research; Risk; Science; Skin; Sodium; Source; Techniques; Time; Tissues; Universities; Urea; Urine; Water; Weight; Work; Youth; blood lipid; bone; bone mass; cardiometabolism; clinical practice; feeding; high salt diet; hypertension control; interest; programs; racial difference; racial disparity; rapid growth; soft tissue; trial comparing; urinary

Program Director/Principal Investigator (Last, First, Middle): Anderson, Cheryl, A. M. Revised abstract: The overall objective of this study is to examine the effects of dietary sodium intake on sodium regulation in adults enrolled in a randomized controlled trial (RCT) recently funded by the Alliance for Potato Research and Education (https://apre.org) -- a non-profit organization funded by the potato industry [PI: Connie Weaver, PhD at Purdue University). The rationale for this work is the strong evidence that dietary sodium has a strong, direct, and progressive relationship with blood pressure, and is causally implicated in hypertension, and subclinical and clinical cardiovascular disease (CVD). There is also considerable interest in the associations of dietary sodium with CVD that are independent of the association with blood pressure. To advance clinical practice and strengthen the evidence supporting public health guidelines, studies are needed to elucidate the mechanisms by which different levels of dietary sodium intake influence sodium regulation. This proposal is timely and relevant as emerging data challenge the dogma that sodium balance is regulated solely by the kidneys and urinary sodium excretion is roughly equivalent to sodium consumed on a day-to-day basis. Our prior work showed racial disparities in sodium retention (i.e., intake minus excretion) in youth consuming the same high sodium diets such that blacks retained much more sodium than whites, but without effects on weight or blood pressure. This finding led us to hypothesize that sodium may be accumulating in the bones of youth, who are black, while rapid growth is occurring. Recently published data in adults suggest there are regulatory sodium clearance mechanisms in soft tissues (i.e., skin and muscle), and that urinary sodium excretion fluctuates in a week-long pattern depending on hormones. An important limitation of the existing body of research related to this proposal is that very few studies have had the capacity to utilize the newest techniques for measuring sodium distribution in soft issues and bone when dietary sodium intake is known. The few studies in this area are mostly in animals. The proposed study fills an important gap as it uses a randomized clinical trial design, with feeding of a controlled diet. We will measure outcomes in blood, urine, muscle, skin, and bone. This will further the science examining whether sodium retention leads to sodium deposits in bone or soft tissues without commensurate water accumulation, a process which likely influences risk of hypertension. In summary, we propose to leverage the infrastructure of an already funded feeding study to examine sodium regulation in adults consuming known amounts of dietary sodium and potassium. The funded trial is focused on examining the difference in potassium retention between potato sources and supplements, and how this affects cardiometabolic outcomes and mineral metabolism. Measurements from urine, skin, muscle, bone, and hormones will be conducted. SPECIFICALLY, WE AIM TO: 1(a): Determine the effects of high and low dietary sodium intake on stores of sodium (i.e., skin, muscle and bone) and on urea production. 1(b): Determine whether sodium distribution mediates the relationship between dietary sodium and blood pressure. Hypotheses: a) Isolated measurement of 24-hour urinary sodium is an inadequate marker of short-term sodium intake, and is an incomplete explanation for the relationship of sodium to blood pressure. Additionally, high sodium intake changes energy metabolism such that urea production and energy expenditure increases; b) Measurements of skin, muscle, and bone are needed to represent sodium distribution and elucidate effects on blood pressure. 2: Determine the effects of high and low sodium intake on urinary sodium excretion and urinary potassium excretion; and whether these effects are modified by hormone regulators (aldosterone, free cortisol, free cortisone, ratio of free cortisone to free cortisol, glucocorticoid, and mineralocorticoid). Hypothesis: Urinary hormone levels will correlate with changes in urinary sodium and potassium excretion; and will vary by high and low sodium intake. Secondary Aim: To examine and report differences by important clinical and demographic factors in sodium regulation and potassium excretion (Aims 1a, 1b, and 2).

项目总监/首席研究员（最后、第一、中间）：Anderson, Cheryl, A. M. 修改后的摘要： 这项研究的总体目标是检查膳食钠摄入量对成人钠调节的影响，该试验最近参加了一项随机对照试验（RCT），该试验由马铃薯研究和教育联盟（https://apre.org）资助，该联盟是一个由马铃薯行业资助的非营利组织[PI：康妮·韦弗（Connie Weaver），普渡大学博士）。这项工作的基本原理是强有力的证据表明膳食钠与血压具有强烈、直接和渐进的关系，并且与高血压、亚临床和临床心血管疾病 (CVD) 存在因果关系。人们对膳食钠与心血管疾病之间的关系也很感兴趣，这种关系与血压无关。为了推进临床实践并加强支持公共卫生指南的证据，需要进行研究来阐明不同膳食钠摄入量影响钠调节的机制。这一提议是及时且相关的，因为新出现的数据挑战了钠平衡仅由肾脏调节的教条，尿钠排泄量大致相当于每天消耗的钠。我们之前的研究表明，摄入相同高钠饮食的青少年在钠保留（即摄入减去排泄）方面存在种族差异，黑人保留的钠比白人多得多，但对体重或血压没有影响。这一发现使我们推测，在快速生长期间，钠可能会在黑人青少年的骨骼中积聚。最近发表的成人数据表明，软组织（即皮肤和肌肉）中存在调节性钠清除机制，并且尿钠排泄量根据激素的不同在一周内波动。与该提案相关的现有研究机构的一个重要限制是，在已知膳食钠摄入量的情况下，很少有研究能够利用最新技术来测量软组织和骨骼中的钠分布。该领域的少数研究大多是在动物身上进行的。拟议的研究填补了一项重要空白，因为它采用随机临床试验设计，并控制饮食喂养。我们将测量血液、尿液、肌肉、皮肤和骨骼的结果。这将进一步科学研究钠潴留是否会导致骨骼或软组织中的钠沉积而没有相应的水积累，这一过程可能会影响高血压的风险。总之，我们建议利用已资助的喂养研究的基础设施来检查摄入已知量膳食钠和钾的成年人的钠调节。这项资助的试验的重点是检查马铃薯来源和补充剂之间钾保留的差异，以及这如何影响心脏代谢结果和矿物质代谢。将对尿液、皮肤、肌肉、骨骼和激素进行测量。具体来说，我们的目标是： 1(a)：确定膳食钠摄入量高和低对钠储存（即皮肤、肌肉和骨骼）和尿素生成的影响。 1(b)：确定钠分布是否介导膳食钠与血压之间的关系。假设：a) 单独测量 24 小时尿钠不足以作为短期钠摄入量的指标，并且不能完整解释钠与血压的关系。此外，高钠摄入会改变能量代谢，导致尿素产生和能量消耗增加； b) 需要测量皮肤、肌肉和骨骼来表示钠分布并阐明对血压的影响。 2：确定高、低钠摄入量对尿钠排泄和尿钾排泄的影响；这些作用是否会受到激素调节剂（醛固酮、游离皮质醇、游离可的松、游离可的松与游离皮质醇的比例、糖皮质激素和盐皮质激素）的影响。假设：尿激素水平与尿钠和钾排泄的变化相关；并会因钠摄入量的高低而变化。次要目标：检查并报告重要临床和人口因素在钠调节和钾排泄方面的差异（目标 1a、1b 和 2）。