AUTHOR=Delgado Spicuzza Jocelyn M. , Gosalia Jigar , Zhong Liezhou , Bondonno Catherine , Petersen Kristina S. , De Souza Mary Jane , Alipour Elmira , Kim-Shapiro Daniel B. , Somani Yasina B. , Proctor David N. 

TITLE=Seven-day dietary nitrate supplementation clinically significantly improves basal macrovascular function in postmenopausal women: a randomized, placebo-controlled, double-blind, crossover clinical trial

JOURNAL=Frontiers in Nutrition

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1359671

DOI=10.3389/fnut.2024.1359671

ISSN=2296-861X

ABSTRACT=<sec id="sec1"><title>Introduction</title><p>Cardiovascular disease (CVD) is the leading cause of death in women, with increased risk following menopause. Dietary intake of beetroot juice and other plant-based nitrate-rich foods is a promising non-pharmacological strategy for increasing systemic nitric oxide and improving endothelial function in elderly populations. The purpose of this randomized, placebo-controlled, double-blind, crossover clinical trial was to determine the effects of short-term dietary nitrate (NO<sub>3</sub><sup>−</sup>) supplementation, in the form of beetroot juice, on resting macrovascular endothelial function and endothelial resistance to whole-arm ischemia–reperfusion (IR) injury in postmenopausal women at two distinct stages of menopause.</p></sec><sec id="sec2"><title>Methods</title><p>Early-postmenopausal [1–6 years following their final menstrual period (FMP), <italic>n</italic> = 12] and late-postmenopausal (6+ years FMP, <italic>n</italic> = 12) women consumed nitrate-rich (400 mg NO<sub>3</sub><sup>−</sup>/70 mL) and nitrate-depleted beetroot juice (approximately 40 mg NO<sub>3</sub><sup>−</sup>/70 mL, placebo) daily for 7 days. Brachial artery flow-mediated dilation (FMD) was measured pre-supplementation (Day 0), and approximately 24 h after the last beetroot juice (BR) dose (Day 8, post-7-day BR). Consequently, FMD was measured immediately post-IR injury and 15 min later (recovery).</p></sec><sec id="sec3"><title>Results</title><p>Results of the linear mixed-effects model revealed a significantly greater increase in resting FMD with 7 days of BR<sub>nitrate</sub> compared to BR<sub>placebo</sub> (mean difference of 2.21, 95% CI [0.082, 4.34], <italic>p</italic> = 0.042); however, neither treatment blunted the decline in post-IR injury FMD in either postmenopausal group. Our results suggest that 7-day BR<sub>nitrate</sub>-mediated endothelial protection is lost within the 24-h period following the final dose of BR<sub>nitrate</sub>.</p></sec><sec id="sec4"><title>Conclusion</title><p>Our findings demonstrate that nitrate-mediated postmenopausal endothelial protection is dependent on the timing of supplementation in relation to IR injury and chronobiological variations in dietary nitrate metabolism.</p></sec><sec id="sec401"><title>Clinical trial registration</title><p><ext-link xlink:href="https://classic.clinicaltrials.gov/ct2/show/NCT03644472" ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink">https://classic.clinicaltrials.gov/ct2/show/NCT03644472</ext-link></p></sec>