Sodium Regulation in Individuals on Known Dietary Sodium Intake

项目负责人/主要研究者（最后一名、第一名、中间名）：安德森、谢丽尔、A。M. 修订摘要： 本研究的总体目标是检查饮食钠摄入量对成人钠调节的影响，该随机对照试验（RCT）最近由马铃薯研究与教育联盟（https：apre.org）资助-马铃薯行业资助的非营利组织[PI：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，并与高血压，亚临床和临床心血管疾病（CVD）有因果关系。也有相当大的兴趣在协会的饮食钠与心血管疾病是独立的与血压。为了推进临床实践并加强支持公共卫生指南的证据，需要进行研究以阐明不同膳食钠摄入水平影响钠调节的机制。这一建议是及时和相关的，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摄入的钠。我们之前的工作显示了钠潴留的种族差异（即，摄入量减去排泄量），使黑人比白人保留更多的钠，但对体重或血压没有影响。这一发现使我们假设，钠可能在黑人青年的骨骼中积累，而快速增长正在发生。最近发表的成人数据表明，软组织中存在调节性钠清除机制（即，皮肤和肌肉），尿钠排泄根据激素以一周的模式波动。与该建议相关的现有研究的一个重要限制是，当膳食钠摄入量已知时，很少有研究能够利用最新技术测量软组织和骨骼中的钠分布。这一领域的少数研究大多是在动物身上进行的。这项拟议的研究填补了一个重要的空白，因为它使用了随机临床试验设计，喂养控制饮食。我们将测量血液、尿液、肌肉、皮肤和骨骼的结果。这将进一步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分积累，这一过程可能会影响高血压的风险。总之，我们建议利用已经资助的喂养研究的基础设施来检查摄入已知量的膳食钠和钾的成人的钠调节。这项资助的试验专注于研究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）：确定高和低膳食钠摄入量对钠储存的影响（即，皮肤、肌肉和骨骼）和尿素产生。1（B）：确定钠分布是否介导膳食钠和血压之间的关系。假设：a）24小时尿钠的单独测量是短期钠摄入的不充分标志，并且是钠与血压关系的不完整解释。此外，高钠摄入改变能量代谢，使得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。第二章：确定高钠和低钠摄入对尿钠排泄和尿钾排泄的影响;以及这些影响是否受到激素调节剂（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率、糖皮质激素和盐皮质激素）的影响。假设：尿激素水平将与尿钠和钾排泄的变化相关;并将因钠摄入量的高低而变化。次要目的：检查并报告重要临床和人口统计学因素在钠调节和钾排泄方面的差异（目的1a、1b和2）。

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).