Beetroot Juice Supplement for Boosting Mucosal Immunity – The NO Cold Study

摘要 呼吸道感染给医疗系统和整个社会造成了相当大的负担，这一点已经被新冠肺炎激怒了。针对呼吸道感染和普通感冒的现有预防性治疗仍然不能令人满意，而且往往得不到遵守。心理因素，如压力，会增加呼吸道感染和普通感冒的风险。这种关系的一个可能机制可能是降低一氧化氮(NO)水平，这是一种第一线防御机制。在心理压力较大的时候，比如学生的期末考试，一氧化氮会减少。在压力期间提高NO水平可能为呼吸道感染提供预防策略，特别是在具有高传播风险的人群中。我们的试验数据表明，甜菜根汁提高了呼出的NO(FeNO)的比例，并缓解了在紧张的期末考试中的感冒症状。本研究提出了一项三臂、双盲、安慰剂对照的试验设计(条件：每日一次有效剂量和一次每日安慰剂剂量，两次每日有效剂量，两次每日安慰剂剂量，每种情况下有50名参与者，总N=150)，以检查甜菜根汁在升高FeNO测定的呼吸道NO，从而减少病毒聚合酶链式反应检测的呼吸道病毒感染方面的有效性。目前的研究将1)证明每天服用甜菜根汁或去硝化安慰剂甜菜根汁7天的试验在逻辑上是可行的，并且在现实生活应激期间具有可接受的依从性；2)产生初步证据，证明甜菜根汁能够增加FeNO的水平，这与使用呼吸道病毒面板的感染减少相关，(生物学特征)，3)检查剂量效应，因为每天两种有效剂量的甜菜根汁在升高FeNO方面可能比每天一剂或一种安慰剂更有效。这项试验将使用一种自然应激的良好控制范例来证明，呼吸道NO的产生是饮食补充硝酸盐对呼吸道感染和常见感冒症状有益效果的关键靶向机制。两所大学将招募参与者，他们在团队整合方面的发现和经验将准备一项常规规模的双臂双盲随机对照临床试验，研究甜菜根汁对呼吸道感染的影响，其中将包括美国西南部更多的招募地点。

Summary Respiratory tract infections cause a considerable burden to health care systems and societies as a whole, which has been exasperated by COVID-19. Available preventative treatments for respiratory infections and the common cold have remained unsatisfactory and are often not adhered to. Psychological factors, such as stress, increase risk for respiratory infections and the common cold. A possible mechanism for this relationship could be reduced levels of nitric oxide (NO), which serve as a first-line defense mechanism. NO is reduced during periods of psychological stress, such as academic finals in students. Boosting levels of NO during periods of stress may provide a prevention strategy for respiratory infections, especially in populations with high transmission risk. Our pilot data suggests that beetroot juice elevates the fraction of exhaled NO (FENO) and attenuates cold symptoms during stressful final exams. The current study proposes a three-arm, double-blinded, and placebo-controlled trial design (conditions: one daily active dose and one daily placebo dose, two daily active doses, two daily placebo doses, with 50 participants in each condition, total N=150), with students under final examination stress, to examine the usefulness of beetroot juice in elevating airway NO measured by FENO and thereby reducing respiratory viral infections tested by viral polymerase chain reaction. The current study will 1) demonstrate that a 7-day trial of daily beetroot juice or de-nitrated placebo beetroot juice is feasible logistically and with acceptable adherence during a period of real-life stress, 2) generate initial evidence for the capacity of beetroot juice to increase elevations in FENO, which correlates with reductions in infection using respiratory viral panel, (biological signature), 3) examine dosage effects, in that two daily active doses of beetroot juice are likely more potent than one daily dose or placebo in elevating FENO. The trial will use a well-controlled paradigm of a naturalistic stress to demonstrate that airway NO production is the critical target mechanism underlying the beneficial effects of dietary nitrate supplementation on respiratory tract infection and common cold symptoms. Two university sites will recruit participants and their findings and experience in team integration will prepare a regular-size two-arm, double-blind randomized controlled clinical trial of beetroot juice effects on respiratory infection, which will include additional recruitment sites across the Southwestern US.