The acute effects of dietary nitrate supplementation on postmenopausal endothelial resistance to ischemia reperfusion injury: A randomized, placebo-controlled, double blind, crossover clinical trial.

Postmenopausal cardiovascular health is a critical determinant of longevity. Consumption of beetroot juice (BR) and other nitrate rich foods is a safe, effective non-pharmacological intervention strategy to increase systemic bioavailability of the vasoprotective molecule, nitric oxide (NO), through the exogenous nitrate (NO3-)-nitrite (NO2-)-NO pathway. We hypothesized that a single dose of nitrate-rich beetroot juice (BRnitrate 600 mg NO3- / 140 mL, BRplacebo ~ 0 mg/ 140 mL) would improve resting endothelial function and resistance to ischemia-reperfusion (IR) injury to a greater extent in early- (1-6 years following their final menstrual period (FMP), n=12) compared to late- (6+ years after FMP, n=12) postmenopausal women. Analyses with general linear models revealed a significant (p<0.05) time*treatment interaction effect for brachial artery adjusted FMD. Pairwise comparisons revealed adjusted FMD was significantly lower following IR-injury in comparison to all other time points with BRplacebo (Early FMD 2.51 ± 1.18%, Late FMD 1.30 ± 1.10, p<0.001) and was lower than post-IR with BRnitrate (Early FMD 3.84 ± 1.21%, Late FMD 3.21 ± 1.13 %, p=0.014). Considering the postmenopausal stage-dependent variations in endothelial responsiveness to dietary nitrate at rest and post-IR, we predict differing mechanisms underpin macrovascular protection against IR injury. NCT03644472.

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

Introduction: 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 (NO3 -) 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. Methods: Early-postmenopausal [1-6 years following their final menstrual period (FMP), n = 12] and late-postmenopausal (6+ years FMP, n = 12) women consumed nitrate-rich (400 mg NO3 -/70 mL) and nitrate-depleted beetroot juice (approximately 40 mg NO3 -/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). Results: Results of the linear mixed-effects model revealed a significantly greater increase in resting FMD with 7 days of BRnitrate compared to BRplacebo (mean difference of 2.21, 95% CI [0.082, 4.34], p = 0.042); however, neither treatment blunted the decline in post-IR injury FMD in either postmenopausal group. Our results suggest that 7-day BRnitrate-mediated endothelial protection is lost within the 24-h period following the final dose of BRnitrate. Conclusion: 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. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT03644472.

Increased pulse wave velocity is related to impaired working memory and executive function in older adults with metabolic syndrome.

Age-related vascular alterations promote the pathogenesis of vascular cognitive impairment (VCI). Cardiovascular risk factors that accelerate vascular aging exacerbate VCI. Metabolic syndrome (MetS) constitutes a cluster of critical cardiovascular risk factors (abdominal obesity, hypertension, elevated triglycerides, elevated fasting glucose, reduced HDL cholesterol), which affects nearly 37% of the adult US population. The present study was designed to test the hypotheses that MetS exacerbates cognitive impairment and that arterial stiffening moderates the association between cognitive dysfunction and MetS in older adults. MetS was defined by the NCEP ATP III guidelines. Cognitive function (digit span and trail-making tests) and brachial-ankle pulse wave velocity (baPWV; a non-invasive clinical measurement of arterial stiffness) were assessed in older adults with MetS and age- and sex-matched controls. Multiple linear regression models were applied to test for the main effects of MetS, baPWV, and their interaction on cognitive performance. Fifty-three participants with MetS (age: 68 ± 8 years) and 39 age-matched individuals without MetS (age: 66 ± 9 years) were enrolled into the study. In adjusted multivariable regression analyses of the digit span backward length score, both MetS (ß = 1.97, p = 0.048) and MetS by baPWV interaction (ß = - 0.001, p = 0.026) were significant predictors. In participants with MetS, higher baPWV was associated with poorer performance on digit span backward length score, a test of working memory (R = - 0.44, p = 0.0012), but there was no association in those without MetS (R = 0.035, p = 0.83). MetS was negatively associated with performance on the digit span backward length score, baPWV was negatively associated with multiple neuropsychological outcomes, and baPWV moderated the association between digit span backward length score and MetS, as individuals with both MetS and higher baPWV had the most impaired cognitive function. Our findings add to the growing body of evidence that individuals with MetS and higher baPWV may be prone to VCI.

Bilateral NIRS measurements of muscle mitochondrial capacity: Feasibility and repeatability.

BACKGROUND: Non-invasive determination of mitochondrial capacity via near infrared spectroscopy (NIRS) typically involves voluntary exercise of a single muscle group followed by as many as 26 brief ischemic cuff occlusions to determine a single recovery rate constant (k). PURPOSE: To determine the within- and between-visit repeatability of a shortened bilateral NIRS protocol, and to establish the feasibility of hamstring k measurements. METHODS: Sixteen young (eight women, eight men; 22 ± 3 years) active adults underwent a bilateral electrical stimulation protocol in which multiple (n = 4) measurements of k for the vastus lateralis (VL) and medial hamstring (MH) muscles were determined on two visits. Repeatability (CV% and intraclass correlations, ICC) and equivalency across visits were assessed for both muscles. RESULTS: Mean k values in the VL were consistent with published values and within-visit ICCs were moderately high for both muscles in both sexes. In men, average k values on visit 2 were within 1% (VL muscle) and 5% (MH muscle) of the values on visit 1 (all p > 0.78). In women, average k values were 10%-15% lower on visit 2 (p = 0.01 and p = 0.15 for MH and VL) with the largest between-visit differences in a subset of participants with the most days between visits. CONCLUSIONS: This bilateral NIRS protocol is time efficient and provides valid estimates of k in both sexes and muscle groups with acceptable within-visit repeatability. Lower than expected between-visit repeatability in some participants reinforces the need for further investigation of this newly developed protocol to identify and control for experimental and behavioral sources of variation.