Sodium Regulation in Individuals on Known Dietary Sodium Intake

项目主任/首席调查员(最后、第一、中间)：安德森、谢丽尔、A.M. 修订摘要： 这项研究的总体目标是在最近由马铃薯研究和教育联盟(https://apre.org))资助的一项随机对照试验(RCT)中检查饮食钠摄入量对成年人钠调节的影响。这项工作的理论基础是强有力的证据表明，膳食钠与血压有强烈、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。饮食中的钠与心血管疾病之间的关联也引起了相当大的兴趣，而这种关联与血压无关。为了推进临床实践并加强支持公共卫生指南的证据，需要研究阐明不同水平的膳食钠摄入量影响钠调节的机制。这一提议是及时和相关的，因为新出现的数据挑战了钠平衡完全由肾脏调节的教条，尿钠排泄大致相当于日常摄入的钠。我们之前的工作表明，在摄入相同高钠饮食的年轻人中，钠保留(即摄入量减去排泄)存在种族差异，因此黑人保留的钠比白人多得多，但对体重或血压没有影响。这一发现让我们假设，钠可能在黑人青年的骨骼中积累，同时发生快速生长。最近公布的成人数据表明，软组织(即皮肤和肌肉)中存在调节的钠清除机制，尿钠排泄根据激素以长达一周的模式波动。与这一提议相关的现有研究的一个重要局限性是，很少有研究能够在已知膳食钠摄入量的情况下，利用最新技术来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，喂养的是受控饮食。我们将测量血液、尿液、肌肉、皮肤和骨骼的结果。这将进一步研究钠滞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，我们建议利用一项已经资助的喂养研究的基础设施来检查摄入已知数量的膳食钠和钾的成年人的钠调节。这项由资金资助的试验重点是检查土豆来源和补充剂之间钾留存的差异，以及这如何影响心脏代谢结果和矿物质代谢。将进行尿液、皮肤、肌肉、骨骼和激素的测量。具体地说，我们的目标是：1(A)：确定高钠和低钠摄入对钠(即皮肤、肌肉和骨骼)储存和尿素产生的影响。1(B)：确定钠分布是否调节膳食钠与血压之间的关系。假设：a)单独测量24小时尿钠不能作为短期钠摄入量的标志，也不能完全解释钠与血压的关系。此外，高钠摄入会改变能量代谢，从而增加尿素的产生和能量消耗；b)需要测量皮肤、肌肉和骨骼来表示钠的分布，并阐明对血压的影响。2：测定高钠和低钠摄入对尿钠排泄和尿钾排泄的影响，以及这些影响是否被激素调节剂(醛固酮、游离皮质醇/游离皮质醇、糖皮质激素和盐皮质激素)所改变。假设：尿液激素水平将与尿钠和钾排泄的变化相关，并将随着钠摄入量的高低而变化。次要目的：检查和报告重要的临床和人口学因素在钠调节和钾排泄方面的差异(目标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).