Dietary Nitrate Supplementation Research Articles

Influence of chronic dietary nitrate on downstream atherogenic metabolites and the enteral microbiome

Abstract Background Inorganic nitrate, which is abundant in leefy green vegetables and mediates cardioprotective effects through nitric oxide related pathways. The enteral microbiome is an emerging key player in cardiovascular diseases and depends on dietary habits. Whether dietary inorganic nitrate influences atherosclerosis-associated microbiome dependent metabolites like short chain fatty acids (SCFA) and trimethylamine N-oxide (TMAO) has not been elucidated so far. Purpose Aim of this study was to investigate the influence of dietary anorganic nitrate intake on atherosclerosis-associated metabolites and the enteral microbiome composition in a healthy trial cohort. Methods In this double-blind randomized controlled trial, we included 30 healthy volunteers, who either received dietary nitrate (0,12 mmol/kg bodyweight) or placebo (equimolar amounts of sodium nitrate) for 30 days. The microbiome metabolites TMAO and SCFA were analysed. Furthermore, upstream enteral microbiome composition was analysed by 16S-rRNA sequencing at baseline and follow-up. Results Systolic blood pressure significantly decreased after nitrate supplementation (baseline 124,73 mmHg vs follow up 120 mmHg, p < 0.05) with no change in controls. Dietary nitrate supplementation significantly increased TMAO levels (control follow-up 343,88 µg/L vs nitrate follow-up 481,15 µg/L, p < 0.05), while SCFA levels remained unchanged. Mechanistically a change in enteral microbiome composition after dietary nitrate supplementation with decreased abundance of the gram-negative bacteria Akkermansia muciniphila was detected, while overall Shannon diversity, richness and evenness did not differ. Conclusions In conclusion, our results indicate that dietary nitrate supplementation alters the enteral microbiome with impact on proatherogenic metabolites. Further work is warranted to investigate the causal relationship between dietary nitrate, the microbiome, downstream metabolites, and the clinical relevance of those findings in a cardiovascular diseased cohort.

The influence of Sex on the Effects of Inorganic Nitrate Supplementation on Muscular Power and Endurance.

Inorganic nitrate (NO3-) supplementation increases nitric oxide (NO) bioavailability and may improve muscular power and endurance, although most studies are in males. Therefore, the present double-blind, randomized, placebo-controlled study examined the effects of NO3- supplementation on isokinetic peak power, maximal voluntary isometric contraction (MVIC) force, muscular endurance (time-to-task failure; TTF), and recovery from fatigue in young females (n=12) and males (n=14). Participants consumed ~13mmol NO3- (BRJ), or an identical NO3--depleted beverage (PL), for ~3 days and 2 hours before testing visits. Plasma nitrate and nitrite were elevated in the BRJ condition (p ≤ 0.05). Peak power (W·kg-1) showed a sex effect (p ≤ 0.05) at all angular velocities and a sex-by-treatment effect at 270 and 360°/sec (p ≤ 0.05). Post hoc analysis revealed no significant differences between treatments (p > 0.05). Estimated maximal knee extension power (Pmax) and maximal knee extension velocity (Vmax) demonstrated no sex, treatment, or sex-by-treatment effect (p > 0.05). There were no significant effects for TTF (F: PL; 269±161 vs BRJ; 277±158s and M: PL; 228±171 vs BRJ; 194±100s; p > 0.05). Cohen's d effect sizes for peak power showed moderate to large effect sizes at 270 (d=0.92) and 360 deg/sec (d=0.81), showing a possible differentiated effect of dietary nitrate in females and males. The present data indicate that NO3- supplementation does not significantly affect knee extensor maximal power, maximal contraction velocity, and muscular endurance in either sex. The sex-dependent response to dietary nitrate supplementation requires further investigation as data on females is scarce.

Effects of low and high dietary nitrate intake on human saliva, plasma and skeletal muscle nitrate and nitrite concentrations and their functional consequences

Dietary nitrate (NO3−) supplementation has been shown to reduce blood pressure (BP), improve exercise performance, and alter the oral microbiome. Following a “control” diet (CON), we manipulated dietary NO3− intake to examine the effect of a short-term (7-day) low NO3− diet (LOW) followed by a 3-day high NO3− diet (HIGH), compared to a 7-day standard (STD) NO3− diet followed by HIGH, on saliva, plasma, and muscle [NO3−] and nitrite ([NO2−]), BP, and cycling exercise performance in healthy young adults. We also examined the effect of LOW on the oral microbiome. Saliva [NO3−] and [NO2−], and plasma [NO3−] were significantly lower than CON following LOW (all P < 0.05) but there was no change in plasma [NO2−] or muscle [NO3−] and [NO2−] (all P > 0.05). Following HIGH, saliva and plasma [NO3−] and [NO2−], and muscle [NO3−], were significantly elevated above CON, LOW and STD (all P < 0.05), but there was no difference between CON-LOW-HIGH and CON-STD-HIGH (P < 0.05). BP and exercise performance were not altered following LOW (P > 0.05). HIGH significantly reduced systolic and diastolic BP compared to CON when preceded by STD (both P < 0.05) but not when preceded by LOW (P > 0.05). Peak (+4 %) and mean (+3 %) power output during sprint cycling was significantly improved following HIGH (both P < 0.05), with no differences between CON-LOW-HIGH and CON-STD-HIGH (both P > 0.05). LOW altered the oral microbiome composition, including decreases in relative abundances of phylum Proteobacteria and genus Neisseria. The findings indicate that a short-term low NO3− diet lowers plasma but not skeletal muscle [NO3−]. The maintenance of plasma [NO2−] and muscle [NO3−] and [NO2−] following LOW may be indicative of their importance to biological functions, including BP regulation and exercise performance.

Effects of Dietary Nitrate Supplementation on Physical Performance and Muscle Strength in Older People—A Systematic Review

ABSTRACTBackgroundSarcopenia, the loss of muscle strength and mass with age, is a major cause of morbidity for older people. Dietary nitrate supplementation has been proposed as an intervention to improve skeletal muscle function via action as nitric oxide (NO) donors. However, the effect of nitrate supplementation on physical performance and muscle strength in older people is unclear. We aimed to systematically review evidence on whether dietary nitrate supplementation improves markers of muscle strength, muscle mass and physical performance in older people.MethodsWe conducted a systematic review of randomised controlled trials according to a prespecified protocol by two reviewers. We included interventional studies using dietary nitrate supplementation, mean participant age of &gt;60 years, with or without muscle weakness. Outcomes of interest were physical performance, muscle strength and muscle mass. Risk of bias was assessed using a modified version of the Cochrane Risk of Bias tool. Results were grouped by intervention and outcome measures and were described by narrative synthesis.ResultsTwenty‐eight studies were included, with a size range of 8–72 participants. Intervention duration ranged from a single dose to 12 weeks. Seven studies were in healthy older people. Most studies had a high or unclear risk of bias; three had a low risk of bias. One‐hundred‐two outcomes were reported; 67 were related to physical performance, and 35 were related to muscle strength. No included study measured muscle mass. Thirty‐three outcomes showed significant improvement, two showed significant worsening and 67 showed no statistically significant difference. Meta‐analysis was not possible due to data heterogeneity. Subgroup analyses for different doses of nitrate (above or below 10 mmol nitrate per day), duration of treatment or specific commonly measured outcomes did not indicate any subgroup more likely to show positive results. The proportion of positive outcomes was similar in studies using beetroot extract, nitrate alone or exercise as a co‐intervention.ConclusionsCurrent evidence is insufficient to decide if dietary nitrate supplementation improves skeletal muscle function in older people. Future studies should be longer, larger and target older people with sarcopenia or frailty.

Relationships Between Changes In Nitric Oxide Biomarkers And Physiological Outcomes Following Dietary Nitrate Supplementation

Relationships Between Changes In Nitric Oxide Biomarkers And Physiological Outcomes Following Dietary Nitrate Supplementation

Acute Dietary Nitrate Supplementation And Cold Pressor Test Cardiovascular Responses In Young Women

Acute Dietary Nitrate Supplementation And Cold Pressor Test Cardiovascular Responses In Young Women

Dietary Nitrate Supplementation Improves Vascular Function Similarly In Older Men And Women

Dietary Nitrate Supplementation Improves Vascular Function Similarly In Older Men And Women

Effects of dietary nitrate, fumaric acid, and methanotrophic bacteria supplementation on rumino-intestinal nutrient metabolism and enteric gas exchange in dairy cows

The objective of the study was to investigate the effects of two approaches for enteric methane (CH4) mitigation and one approach for redirection of excess hydrogen (H2) resulting from CH4 inhibition, on dairy cows’ gas exchange and nutrient digestibility. Approaches for CH4 mitigation were methanotrophic bacteria supplementation and dietary nitrate, whereas the approach for H2 redirection was nitrate combined with fumaric acid. An incomplete 6 × 6 Latin square design experiment was conducted with 4 periods of 21 d using 6 rumen, duodenum, and ileum cannulated Danish Holstein cows with DIM of 123 ± 64.8 d (mean ± SD) and the milk yield was 33.6 ± 9.39 kg/d at beginning of experiment. The treatments were organized in a 2 × 3 factorial arrangement, where the first factor represented treatments without or with methanotrophic bacteria supplementation (MET), and the second factor represented 3 different dietary additive supplementations (DIET). These were a basal diet (BAS; no additives), a diet with nitrate (NIT; 10 g nitrate/kg dry matter (DM)), and a diet with nitrate combined with fumaric acid (NIT-F; NIT + 15 g fumaric acid/kg DM). Cows had ad libitum access to diets with a forage to concentrate ratio of 60 to 40 on dry matter basis. Following adaptation to experimental diets, samples of rumen fluid, digesta from duodenum and ileum, and feces were collected to estimate nutrient digestibility using Cr2O3 and TiO2 as external flow markers. Then, gas exchanges were measured in respiration chambers. There was no CH4 mitigating effect of MET. Nitrate reduced CH4 production (g/d), yield (g/kg DMI), and intensity (g/kg ECM) by 19.5, 11.9, and 17.2 %, respectively, whereas H2 yield (g/kg DMI) was increased by 261 %. Ruminal redox value was decreased by nitrate, and individual rumen volatile fatty acid proportions reflected a more reduced rumen environment although propionate proportions decreased. Nutrient digestibility was not affected by nitrate although microbial CP efficiency (g of microbial CP/kg true rumen digested organic matter) was decreased. Supplementing fumaric acid in combination with nitrate decreased H2 production by 26.8 % compared to nitrate fed cows, and this was associated with increased propionate concentrations. However, there was no effect on H2 emission when corrected for dry matter intake (DMI) or energy-corrected milk (ECM) yield. There were no effects of any of the treatments on DMI or ECM yield. In conclusion, the results demonstrated a CH4 mitigating effect of nitrate supplementation resulting in increased H2 emission. The effects on nutrient digestibility and rumen fermentation were minor. Fumaric acid supplementation redirected some H2 to propionate, although the efficiency was small. Supplementation of methanotrophic bacteria did not suppress CH4 emission.

Effects of dietary nitrate or nitrite supplementation on inhibitory avoidance task and pentylenetetrazole-induced clonic seizure threshold in mice

Effects of dietary nitrate or nitrite supplementation on inhibitory avoidance task and pentylenetetrazole-induced clonic seizure threshold in mice

Nitrate and Nitrite Concentrations in Fingertip Serum Following Beetroot Juice Ingestion Correlate with Those in Venous Plasma.

Dietary nitrate (NO3-) supplementation can offer health benefit and improve exercise performance by increasing nitric oxide (NO) through NO3--nitrite (NO2-)-NO pathway. Individuals may benefit from dietary NO3- supplementation by monitoring blood [NO3-] and [NO2-], although a simple and practical method for assessing blood [NO3-] and [NO2-] has not been established. We examined whether fingertip serum samples could substitute for venous plasma samples in assessing [NO3-] and [NO2-]. Ten young adults consumed 140 mL of nitrate-rich beetroot juice. Fingertip serum and venous plasma samples were collected at baseline and every hour for up to 4 h after ingestion. [NO3-] and [NO2-] were similar between samples at baseline, whereas they were higher in fingertip serum throughout the post-ingestion periods. Significant correlations existed between fingertip serum vs. venous plasma for both [NO3-] and [NO2-] throughout post-drink periods, except [NO3-] assessed at 2 and 4 h after ingestion of beetroot juice. We show that although fingertip serum [NO3-] and [NO2-] overestimate those measured by venous plasma after dietary NO3- intake (125-141% and 156-183% of venous values), [NO3-] and [NO2-] in fingertip serum samples may be utilized for assessing blood [NO3-] and [NO2-] levels, although [NO3-] assessment may lack precision compared to [NO2-].

Cerebral microvascular changes in healthy carriers of the APOE-ɛ4 Alzheimer's disease risk gene.

APOE-ɛ4 is a genetic risk factor for Alzheimer's disease (AD). AD is associated with reduced cerebral blood flow (CBF) and with microvascular changes that limit the transport of oxygen from blood into brain tissue: reduced microvascular cerebral blood volume and high relative transit time heterogeneity (RTH). Healthy APOE-ɛ4 carriers reveal brain regions with elevated CBF compared with carriers of the common ɛ3 allele. Such asymptomatic hyperemia may reflect microvascular dysfunction: a vascular disease entity characterized by suboptimal tissue oxygen uptake, rather than limited blood flow per se. Here, we used perfusion MRI to show that elevated regional CBF is accompanied by reduced capillary blood volume in healthy APOE-ɛ4 carriers (carriers) aged 30-70 years compared with similarly aged APOE-ɛ3 carriers (noncarriers). Younger carriers have elevated hippocampal RTH and more extreme RTH values throughout both white matter (WM) and cortical gray matter (GM) compared with noncarriers. Older carriers have reduced WM CBF and more extreme GM RTH values than noncarriers. Across all groups, lower WM and hippocampal RTH correlate with higher educational attainment, which is associated with lower AD risk. Three days of dietary nitrate supplementation increased carriers' WM CBF but caused older carriers to score worse on two of six aggregate neuropsychological scores. The intervention improved late recall in younger carriers and in noncarriers. The APOE-ɛ4 gene is associated with microvascular changes that may impair tissue oxygen extraction. We speculate that vascular risk factor control is particularly important for APOE-ɛ4 carriers' healthy aging.

Effects of Dietary Nitrate Supplementation on High-Intensity Cycling Sprint Performance in Recreationally Active Adults: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis investigated the influence of dietary nitrate supplementation on performance metrics during cycling sprint exercise according to the PRISMA guidelines. Searches were conducted on MEDLINE, PubMed, ScienceDirect, Scopus, and SPORTDiscus databases up to September 2023. Inclusion criteria were healthy recreationally active men and women who consumed nitrate-rich and nitrate-deficient beetroot juice to assess performance outcomes of mean power, peak power, time-to-peak power, and minimum power during 30-s cycling sprints. Risk of bias was assessed using the Cochrane Risk of Bias 2 and TESTEX tools and funnel plots. A random effects model was performed on six studies and showed that dietary nitrate had significant effects on time-to-peak power (SMD: -0.66, 95% CI: -1.127 to -0.192, p = 0.006) but not on mean power, peak power, or minimum power. Subgroup analysis revealed that an acute low nitrate dose improved time-to-peak power (SMD: -0.977, 95% CI: -1.524 to -0.430, p < 0.001) but not after a multiday moderate nitrate dose (SMD: -0.177, 95% CI: -0.619 to -0.264, p = 0.431). These data suggest that acute nitrate supplementation can benefit time-to-peak power during 30-s cycling sprints, but due to the limited availability of data and heterogeneity in methodology, these results should be interpreted with caution. There was insufficient data on women to analyze sex-based differences. Future studies are required to provide insight on how supplementation regimen and population impact the effects of dietary nitrate for enhancing cycling sprint performance.

Effects of short-term dietary nitrate supplementation on exercise and coronary blood flow responses in patients with peripheral artery disease.

Peripheral arterial disease (PAD) is a prevalent vascular disorder characterized by atherosclerotic occlusion of peripheral arteries, resulting in reduced blood flow to the lower extremities and poor walking ability. Older patients with PAD are also at a markedly increased risk of cardiovascular events, including myocardial infarction. Recent evidence indicates that inorganic nitrate supplementation, which is abundant in certain vegetables, augments nitric oxide (NO) bioavailability and may have beneficial effects on walking, blood pressure, and vascular function in patients with PAD. We sought to determine if short-term nitrate supplementation (via beetroot juice) improves peak treadmill time and coronary hyperemic responses to plantar flexion exercise relative to placebo (nitrate-depleted juice) in older patients with PAD. The primary endpoints were peak treadmill time and the peak coronary hyperemic response to plantar flexion exercise. Eleven PAD patients (52-80 yr.; 9 men/2 women; Fontaine stage II) were randomized (double-blind) to either nitrate-rich (Beet-IT, 0.3 g inorganic nitrate twice/day; BRnitrate) or nitrate-depleted (Beet-IT, 0.04 g inorganic nitrate twice/day, BRplacebo) beetroot juice for 4 to 6 days, followed by a washout of 7 to 14 days before crossing over to the other treatment. Patients completed graded plantar flexion exercise with their most symptomatic leg to fatigue, followed by isometric handgrip until volitional fatigue at 40% of maximum on day 4 of supplementation, and a treadmill test to peak exertion 1-2 days later while continuing supplementation. Hemodynamics and exercise tolerance, and coronary blood flow velocity (CBV) responses were measured. Although peak walking time and claudication onset time during treadmill exercise did not differ significantly between BRplacebo and BRnitrate, the diastolic blood pressure response at the peak treadmill walking stage was significantly lower in the BRnitrate condition. Increases in CBV from baseline to peak plantar flexion exercise after BRplacebo and BRnitrate showed a trend for a greater increase in CBV at the peak workload of plantar flexion with BRnitrate (p = 0.06; Cohen's d = 0.56). Overall, these preliminary findings suggest that inorganic nitrate supplementation in PAD patients is safe, well-tolerated, and may improve the coronary hyperemic and blood pressure responses when their calf muscles are most predisposed to ischemia.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT02553733.

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-pharmaceutical intervention to increase systemic bioavailability of the vasoprotective molecule, nitric oxide, through the exogenous nitrate (NO3 -)-nitrite (NO2 -)-nitric oxide (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-postmenopausal (1-6 years following their final menstrual period (FMP), n=12) compared to late-postmenopausal (6+years after FMP, n=12) women. Analyses with general linear models revealed a significant (p<0.05) time*treatment interaction effect for brachial artery adjusted flow-mediated dilation (FMD). Pairwise comparisons revealed that 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). A single dose of BRnitrate significantly increased resting macrovascular function in the late postmenopausal group only (p=0.005). Considering the postmenopausal stage-dependent variations in endothelial responsiveness to dietary nitrate, we predict differing mechanisms underpin macrovascular protection against IR injury.

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

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. 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 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. 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. https://classic.clinicaltrials.gov/ct2/show/NCT03644472.

Effects of dietary nitrate supplementation on markers of oral health: A systematic review

The oral cavity is a vital part of the digestive system. Poor oral health can impact an individual’s ability to eat and has been associated with increased risk of non-communicable diseases and reduced longevity. Conversely, positive oral health has been associated with improved cardiometabolic, cognitive and systemic health and greater longevity. Consumption of dietary nitrate, which is processed in the mouth into nitrite, and is subsequently converted into nitric oxide (NO) in the body (1), has been demonstrated to reduce blood pressure, improve endothelial function, and enhance exercise performance. Interestingly, recent studies suggest that nitrate consumption could also positively modulate markers of oral health (2). To our knowledge, no systematic review has been published examining the effect of inorganic dietary nitrate on oral health. However, this could be valuable to summarise current state of the knowledge, identify effect modifiers and highlight gaps for future research. Therefore, this systematic review aims to investigate the effects of dietary nitrate supplements on markers of oral health in vivo in randomised controlled trials (RCTs).This study was pre-registered with PROSPERO (CRD42023411159). Five databases (PubMed, The Cochrane Library, CINAHL, MEDLINE, and SPORTDiscus) were searched from inception until March 2023 to identify studies that met the following criteria: adult participants (≥ 18 years) and RCTs investigating the effects of oral dietary nitrate versus placebo on markers of oral health. A narrative synthesis of data was conducted. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool.Nine articles reporting data on 284 participants were included. Nitrate was provided via beetroot juice (six studies), a beetroot-derived supplement dissolved in mineral water (one study), and lettuce juice (two studies). The duration of the interventions ranged from one day to a maximum of six weeks. Dietary nitrate supplementation increased the relative abundance of several individual bacterial genera including Neisseria (increased in three studies) and Rothia (increased in three studies). Dietary nitrate supplementation increased salivary pH (increased in two studies) and decreased salivary acidification resulting from the consumption of a sugar-sweetened beverage (decreased in two studies). Furthermore, dietary nitrate supplementation resulted in a decrease in the gingival inflammation index in one study. Overall, the risk of bias in studies was mixed. One study had a low risk of bias, while the rest were rated as having some concerns. No study was considered to have a high risk of bias.The results show that dietary nitrate is a potential nutritional strategy that can potentially benefit oral health by modifying the oral microbiome, altering salivary pH, and minimising gingival inflammation.

Effect of Acute Dietary Nitrate Supplementation on the Changes in Calf Venous Volume during Postural Change and Skeletal Muscle Pump Activity in Healthy Young Adults.

Dietary nitrate (NO3-) supplementation is known to enhance nitric oxide (NO) activity and acts as a vasodilator. In this randomized crossover study, we investigated the effect of inorganic NO3- supplementation on the changes in calf venous volume during postural change and subsequent skeletal muscle pump activity. Fifteen healthy young adults were assigned to receive beetroot juice (BRJ) or a NO3--depleted control beverage (prune juice: CON). Two hours after beverage consumption, the changes in the right calf volume during postural change from supine to upright and a subsequent right tiptoe maneuver were measured using venous occlusion plethysmography. The increase in calf volume from the supine to upright position (total venous volume [VV]) and the decrease in calf volume during the right tiptoe maneuver (venous ejection volume [Ve]) were calculated. Plasma NO3- concentration was higher in the BRJ group than in the CON group 2 h after beverage intake (p < 0.05). However, VV and Ve did not differ between CON and BRJ. These results suggest that acute intake of BRJ may enhance NO activity via the NO3- → nitrite → NO pathway but does not change calf venous pooling due to a postural change or the calf venous return due to skeletal muscle pump activity in healthy young adults.

Lifestyle Intervention Improves Parasympathetic Activity in Hypertrophic Cardiomyopathy

Background A limited number of studies have investigated the effects of lifestyle interventions in hypertrophic cardiomyopathy (HCM). This study evaluated the effect of a novel lifestyle intervention incorporating physical activity (PA) and dietary nitrate supplementation on heart rate variability (HRV) and haemodynamic measures in HCM. Methods Twenty-eight individuals with HCM were randomised into either the intervention or control group. Frequency-domain HRV measures including low frequency power (LF), high frequency power (HF) and LF/HF were recorded at rest using bioimpedance. Non-invasive haemodynamic variables were recorded at rest using bioreactance. Participants in the intervention group consumed 6 mmol of nitrate daily (concentrated beetroot juice) and were instructed to increase and maintain daily PA by ≥ 2000 steps/day above baseline for 16 weeks. Control group participants retained their usual lifestyle and monitored daily step counts. Results There was a significant increase in post-intervention HF power (7.54 ± 2.14 vs 8.78 ± 1.60 ms2, P &lt; .01) and LF power (6.89 ± 2.33 vs 8.17 ± 1.55, P &lt; .01) in the intervention but not in the control group. Resting mean arterial blood pressure (MABP) in the intervention group significantly reduced at follow-up (108 ± 6 vs 102 ± 7 mmHg, P &lt; .01). Conclusions A novel lifestyle intervention including PA and dietary nitrate supplementation enhanced parasympathetic activity and resting MABP in HCM.

Influence of acute dietary nitrate supplementation on oxygen delivery/consumption and critical impulse during maximal effort forearm exercise in males: a randomized crossover trial.

Beetroot juice supplementation (BRJ) should increase nitric oxide bioavailability under conditions of muscle deoxygenation and acidosis that are a normal consequence of the maximal effort exercise test used to identify forearm critical impulse. We hypothesized BRJ would improve oxygen delivery:demand matching and forearm critical impulse performance. Healthy males (20.8±2.4 years) participated in a randomized crossover trial between October 2017 and May 2018 (Queen's University, Kingston, ON). Participants completed 10 min of rhythmic maximal effort forearm handgrip exercise 2.5 h post placebo (PL) vs. BRJ (9 completed PL/BRJ vs. 4 completed BRJ/PL) within a 2 week period. Data are presented as mean±SD. There was a main effect of drink (PL>BRJ) for oxygen extraction (P=0.033, ηp2=0.351) and oxygen consumption/force (P=0.017, ηp2=0.417). There was a drink × time interaction (PL>BRJ) for oxygen consumption/force (P=0.035, ηp2=0.216) between 75 and 360s (1.25-6min) from exercise onset. BRJ did not influence oxygen delivery (P=0.953, ηp2=0.000), oxygen consumption (P=0.064, ηp2=0.278), metabolites ((lactate) (P=0.196, ηp2=0.135), pH (P=0.759, ηp2=0.008)) or power-duration performance parameters (critical impulse (P=0.379, d=0.253), W' (P=0.733, d=0.097)). BRJ during all-out handgrip exercise does not influence oxygen delivery or exercise performance. Oxygen cost of contraction with BRJ is reduced as contraction impulse is declining during maximal effort exercise resulting in less oxygen extraction.

Relationships between nitric oxide biomarkers and physiological outcomes following dietary nitrate supplementation

Dietary nitrate (NO3−) supplementation can increase nitric oxide (NO) bioavailability, reduce blood pressure (BP) and improve muscle contractile function in humans. Plasma nitrite concentration (plasma [NO2−]) is the most oft-used biomarker of NO bioavailability. However, it is unclear which of several NO biomarkers (NO3−, NO2−, S-nitrosothiols (RSNOs)) in plasma, whole blood (WB), red blood cells (RBC) and skeletal muscle correlate with the physiological effects of acute and chronic dietary NO3− supplementation. Using a randomized, double-blind, crossover design, 12 participants (9 males) consumed NO3−-rich beetroot juice (BR) (∼12.8 mmol NO3−) and NO3−-depleted placebo beetroot juice (PL) acutely and then chronically (for two weeks). Biological samples were collected, resting BP was assessed, and 10 maximal voluntary isometric contractions of the knee extensors were performed at 2.5–3.5 h following supplement ingestion on day 1 and day 14. Diastolic BP was significantly lower in BR (−2 ± 3 mmHg, P = 0.03) compared to PL following acute supplementation, while the absolute rate of torque development (RTD) was significantly greater in BR at 0–30 ms (39 ± 57 N m s−1, P = 0.03) and 0–50 ms (79 ± 99 N m s−1, P = 0.02) compared to PL following two weeks supplementation. Greater WB [RSNOs] rather than plasma [NO2−] was correlated with lower diastolic BP (r = −0.68, P = 0.02) in BR compared to PL following acute supplementation, while greater skeletal muscle [NO3−] was correlated with greater RTD at 0–30 ms (r = 0.64, P=0.03) in BR compared to PL following chronic supplementation. We conclude that [RSNOs] in blood, and [NO3−] in skeletal muscle, are relevant biomarkers of NO bioavailability which are related to the reduction of BP and the enhanced muscle contractile function following dietary NO3− ingestion in humans.