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

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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.