The Effect of Dietary Inorganic Nitrate Supplementation on Cardiac Function During Submaximal Exercise in Men With Heart Failure With Reduced Ejection Fraction (Hfref): A Pilot Study

Heart failure with reduced ejection fraction (HFrEF) is a common end point for patients with coronary artery disease and it is characterized by exercise intolerance due, in part, to a reduction in cardiac output. Nitric oxide (NO) plays a vital role in cardiac function and patients with HFrEF have been identified as having reduced vascular NO. This pilot study aimed to investigate if nitrate supplementation could improve cardiac measures during acute, submaximal exercise. Five male participants (61 ± 3 years) with HFrEF (EF 32 ± 2.2%) completed this pilot study. All participants supplemented with inorganic nitrate (beetroot juice) or a nitrate-depleted placebo for ~13 days prior to testing. Participants completed a three-stage submaximal exercise protocol on a recumbent cycle ergometer with simultaneous echocardiography for calculation of cardiac output (Q), stroke volume (SV), and total peripheral resistance (TPR). Heart rate and blood pressure were measured at rest and during each stage. Both plasma nitrate (mean = ~1028%, p = 0.004) and nitrite (mean = ~109%, p = 0.01) increased following supplementation. There were no differences between interventions at rest, but the percent change in SV and Q from rest to stage two and stage three of exercise was higher following nitrate supplementation (all p > 0.05, ES > 0.8). Both interventions showed decreases in TPR during exercise, but the percent reduction TPR in stages two and three was greater following nitrate supplementation (p = 0.09, ES = 0.98 and p = 0.14, ES = 0.82, respectively). There were clinically relevant increases in cardiac function during exercise following supplementation with nitrate. The findings from this pilot study warrant further investigation in larger clinical trials

Changes in body posture alter plasma nitrite but not nitrate concentration in humans

PURPOSE: This study evaluated the change (Δ) in plasma volume (PV), nitrate [NO3-], and nitrite [NO2-] concentration following changes in posture in the presence and absence of elevated plasma [NO3-] and [NO2-] METHODS: Fourteen healthy participants completed two trials that were preceded by either supplementation with NO3--rich beetroot juice (BR; total of ∼31 mmol NO3-) or no supplementation (CON). Both trials comprised 30 min of lying supine followed by 2 min of standing, 2 min of sitting and 5 min of sub-maximal cycling. Measurements of plasma [NO3-] and [NO2-] were made by gas-phase chemiluminescence and ΔPV was estimated using the Dill and Costill method.RESULTS: Plasma [NO2-] decreased from baseline (CON: 120 ± 49 nM, BR: 357 ± 129 nM) after lying supine for 30 min (CON 77 ± 30 nM; BR 231 ± 92 nM, both P 0.05). PV increased from baseline during the supine phase before decreasing upon standing, sitting, and exercise in both trials (all

Dietary nitrate supplementation in cardiovascular health: An ergogenic aid or exercise therapeutic?

Oral consumption of inorganic nitrate, which is abundant in green leafy vegetables and roots, has been shown to increase circulating plasma nitrite concentration, which can be converted to nitric oxide in low oxygen conditions. The associated beneficial physiological effects include a reduction in blood pressure, modification of platelet aggregation, and increases in limb blood flow. There have been numerous studies of nitrate supplementation in healthy recreational and competitive athletes; however, the ergogenic benefits are currently unclear due to a variety of factors including small sample sizes, different dosing regimens, variable nitrate conversion rates, the heterogeneity of participants’ initial fitness levels, and the types of exercise tests used. In clinical populations, the study results seem more promising, particularly in patients with cardiovascular diseases who typically present with disruptions in the ability to transport oxygen from the atmosphere to working tissues and reduced exercise tolerance. Many of these disease-related, physiological maladaptations, including endothelial dysfunction, increased reactive oxygen species, reduced tissue perfusion, and muscle mitochondrial dysfunction, have been previously identified as potential targets for nitric oxide restorative effects. This review is the first of its kind to outline the current evidence for inorganic nitrate supplementation as a therapeutic intervention to restore exercise tolerance and improve quality of life in patients with cardiovascular diseases. We summarize the factors that appear to limit or maximize its effectiveness and present a case for why it may be more effective in patients with cardiovascular disease than as ergogenic aid in healthy populations

Acute Dietary Nitrate Supplementation Improves Flow Mediated Dilatation of the Superficial Femoral Artery in Healthy Older Males

Aging is often associated with reduced leg blood flow, increased arterial stiffness, and endothelial dysfunction, all of which are related to declining nitric oxide (NO) bioavailability. Flow mediated dilatation (FMD) and passive leg movement (PLM) hyperaemia are two techniques used to measure NO-dependent vascular function. We hypothesised that acute dietary nitrate (NO3−) supplementation would improve NO bioavailability, leg FMD, and PLM hyperaemia. Fifteen healthy older men (69 ± 4 years) attended two experiment sessions and consumed either 140 mL of concentrated beetroot juice (800 mg NO3−) or placebo (NO3−-depleted beetroot juice) in a randomised, double blind, cross-over design study. Plasma nitrite (NO2−) and NO3−, blood pressure (BP), augmentation index (AIx75), pulse wave velocity (PWV), FMD of the superficial femoral artery, and PLM hyperaemia were measured immediately before and 2.5 h after consuming NO3− and placebo. Placebo had no effect but NO3− led to an 8.6-fold increase in plasma NO2−, which was accompanied by an increase in FMD (NO3−: +1.18 ± 0.94% vs. placebo: 0.23 ± 1.13%, p = 0.002), and a reduction in AIx75 (NO3−: −8.7 ± 11.6% vs. placebo: −4.6 ± 5.5%, p = 0.027). PLM hyperaemia, BP, and PWV were unchanged during both trials. This study showed that a dose of dietary NO3− improved NO bioavailability and enhanced endothelial function as measured by femoral artery FMD. These findings provide insight into the specific central and peripheral vascular responses to dietary NO3− supplementation in older adult

Beetroot juice versus chard gel: A pharmacokinetic and pharmacodynamic comparison of nitrate bioavailability

Dietary supplementation with inorganic nitrate (NO3?) has been shown to induce a multitude of advantageous cardiovascular and metabolic responses during rest and exercise. While there is some suggestion that pharmacokinetics may differ depending on the NO3? source ingested, to the best of our knowledge this has yet to be determined experimentally. Here, we compare the plasma pharmacokinetics of NO3?, nitrite (NO2?), and total nitroso species (RXNO) following oral ingestion of either NO3? rich beetroot juice (BR) or chard gels (GEL) with the associated changes in blood pressure (BP). Repeated samples of venous blood and measurements of BP were collected from nine healthy human volunteers before and after ingestion of the supplements using a cross-over design. Plasma concentrations of RXNO and NO2? were quantified using reductive gas-phase chemiluminescence and NO3? using high pressure liquid ion chromatography. We report that, [NO3?] and [NO2?] were increased and systolic BP reduced to a similar extent in each experimental arm, with considerable inter-individual variation. Intriguingly, there was a greater increase in [RXNO] following ingestion of BR in comparison to GEL, which may be a consequence of its higher polyphenol content. In conclusion, our data suggests that while differences in circulating NO2? and NO3? concentrations after oral administration of distinct NO3?-rich supplementation sources are moderate, concentrations of metabolic by-products may show greater-than-expected variability; the significance of the latter observation for the biological effects under study remains to be investigated

Transforming growth factor Beta 1 alters glucose uptake but not insulin signalling in human primary myotubes from women with and without polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS), commonly have profound skeletal muscle insulin resistance which can worsen other clinical features. The heterogeneity of the condition has made it challenging to identify the precise mechanisms that cause this insulin resistance. A possible explanation for the underlying insulin resistance may be the dysregulation of Transforming Growth Factor-beta (TGFβ) signalling. TGFβ signalling contributes to the remodelling of reproductive and hepatic tissues in women with PCOS. Given the systemic nature of TGFβ signalling and its role in skeletal muscle homeostasis, it may be possible that these adverse effects extend to other peripheral tissues. We aimed to determine if TGFβ1 could negatively regulate glucose uptake and insulin signalling in skeletal muscle of women with PCOS. We show that both myotubes from women with PCOS and healthy women displayed an increase in glucose uptake, independent of changes in insulin signalling, following short term (16 hr) TGFβ1 treatment. This increase occurred despite pro-fibrotic signalling increasing via SMAD3 and connective tissue growth factor in both groups following treatment with TGFβ1. Collectively, our findings show that short-term treatment with TGFβ1 does not appear to influence insulin signalling or promote insulin resistance in myotubes. These findings suggest that aberrant TGFβ signalling is unlikely to directly contribute to skeletal muscle insulin resistance in women with PCOS in the short term but does not rule out indirect or longer-term effects

Efficacy of high-intensity interval training for improving mental health and health-related quality of life in women with polycystic ovary syndrome

Women with PCOS have substantially greater symptoms of depression and anxiety, and a lower health-related quality of life (HRQoL) compared to women without PCOS. The aim of this study was to determine if high-intensity interval training (HIIT) could provide greater improvements in mental health outcomes than standard moderate-intensity continuous training (MICT). Twenty-nine overweight women with PCOS aged 18–45 years were randomly assigned to 12 weeks of either MICT (60–75% HRpeak, N = 15) or HIIT (> 90% HRpeak, N = 14). Outcome measures included symptoms of depression, anxiety and stress (DASS-21), general HRQoL (SF-36) and PCOS specific HRQoL (PCOSQ) collected at baseline and post-intervention. Reductions in depression (Δ − 1.7, P = 0.005), anxiety (Δ − 3.4, P < 0.001) and stress (Δ − 2.4, P = 0.003) scores were observed in the HIIT group, while MICT only resulted in a reduction in stress scores (Δ − 2.9, P = 0.001). Reductions in anxiety scores were significantly higher in the HIIT group compared to the MICT group (β = − 2.24, P = 0.020). Both HIIT and MICT significantly improved multiple domain scores from the SF-36 and PCOSQ. This study highlights the potential of HIIT for improving mental health and HRQoL in overweight women with PCOS. HIIT may be a viable strategy to reduce symptoms of depression and anxiety in women with PCOS, however, large-scale studies are required to confirm these findings. Trial registration number: ACTRN12615000242527

The effects of two different doses of ultraviolet-A light exposure on nitric oxide metabolites and cardiorespiratory outcomes

PURPOSE: The present study investigated different doses of ultraviolet-A (UV-A) light on plasma nitric oxide metabolites and cardiorespiratory variables.METHODS: Ten healthy male participants completed three experimental conditions, 7 days apart. Participants were exposed to no light (CON); 10 J cm2 (15 min) of UV-A light (UVA10) and 20 J cm2 (30 min) of UV-A light (UVA20) in a randomized order. Plasma nitrite [NO2-] and nitrate [NO3-] concentrations, blood pressure (BP), and heart rate (HR) were recorded before, immediately after exposure and 30 min post-exposure. Whole body oxygen utilization ([Formula: see text]), resting metabolic rate (RMR) and skin temperature were recorded continuously.RESULTS: None of the measured parameters changed significantly during CON (all P?>?0.05). [Formula: see text] and RMR were significantly reduced immediately after UVA10 (P??0.05). Immediately after exposure to UVA20, plasma [NO2-] was higher (P?=?0.014) and [Formula: see text] and RMR tended to be lower compared to baseline (P?=?0.06). There were no differences in [NO2-] or [Formula: see text] at the 30 min time point in any condition. UV-A exposure did not alter systolic BP, diastolic BP or MAP (all P?>?0.05). UV-A light did not alter plasma [NO3-] at any time point (all P?>?0.05).CONCLUSIONS: This study demonstrates that a UV-A dose of 20 J cm2 is necessary to increase plasma [NO2-] although a smaller dose is capable of reducing [Formula: see text] and RMR at rest. Exposure to UV-A did not significantly reduce BP in this cohort of healthy adults. These data suggest that exposure to sunlight has a meaningful acute impact on metabolic function

Lower limb ischemic preconditioning combined with dietary nitrate supplementation does not influence time-trial performance in well-trained cyclists

OBJECTIVES: Dietary nitrate (NO3-) supplementation and ischaemic preconditioning (IPC) can independently improve exercise performance. The purpose of this study was to explore whether NO3- supplementation, ingested prior to an IPC protocol, could synergistically enhance parameters of exercise.DESIGN: Double-blind randomized crossover trial.METHODS: Ten competitive male cyclists (age 34±6years, body mass 78.9±4.9kg, V⋅O2peak 55±4 mLkgmin-1) completed an incremental exercise test followed by three cycling trials comprising a square-wave submaximal component and a 16.1km time-trial. Oxygen uptake (V⋅O2) and muscle oxygenation kinetics were measured throughout. The baseline (BASE) trial was conducted without any dietary intervention or IPC. In the remaining two trials, participants received 3×5min bouts of lower limb bilateral IPC prior to exercise. Participants ingested NO3--rich gel (NIT+IPC) 90min prior to testing in one trial and a low NO3- placebo in the other (PLA+IPC). Plasma NO3- and nitrite (NO2-) were measured immediately before and after application of IPC.RESULTS: Plasma [NO3-] and [NO2-] were higher before and after IPC in NIT+IPC compared to BASE (P0.4). Performance in the time-trial was similar between trials (BASE 1343±72s, PLA+IPC 1350±75s, NIT+IPC 1346±83s, P=0.98).CONCLUSIONS: Pre-exercise IPC did not improve sub-maximal exercise or performance measures, either alone or in combination with dietary NO3- supplementation

The effectiveness of high intensity intermittent training on metabolic, reproductive and mental health in women with polycystic ovary syndrome: study protocol for the iHIT- randomised controlled trial

Abstract Background Polycystic ovary syndrome (PCOS) is a reproductive-metabolic condition. Insulin resistance is a hallmark of PCOS and is related to increased hyperandrogenism that drives inherent metabolic, reproductive and psychological features of the syndrome. Insulin resistance in women with PCOS is managed by weight loss, lifestyle interventions (i.e. exercise, diet) and insulin-sensitising medications. This manuscript describes the protocol of our study evaluating the effectiveness of high intensity intermittent training (HIIT) or moderate intensity exercise on cardiometabolic, reproductive and mental health in overweight women with PCOS. Methods/design We will employ a three arm, parallel-group, randomised controlled trial recruiting 60 women diagnosed with PCOS, aged between 18 and 45 years and with a body mass index (BMI) greater than 25 kg/m2. Following screening and baseline testing, women will be randomised by simple randomisation procedure using computer generated sequence allocation to undergo one of two 12-week supervised interventions: either HIIT or moderate intensity exercise (standard supervised exercise), or to standard care [Con] (unsupervised lifestyle advice) at a 1:1:1 allocation ratio. The primary outcome for this trial is to measure the improvements in metabolic health; specifically changes in insulin sensitivity in response to different exercise intensities. Baseline and post-intervention testing include anthropometric measurements, cardiorespiratory fitness testing, reproductive hormone profiles (anti-müllerian hormone and steroid profiles), metabolic health, health-related quality of life and mental health questionnaires and objective and subjective lifestyle monitoring. Reporting of the study will follow the CONSORT statement. Discussion This trial aims to demonstrate the comparative efficacy and maintenance of different exercise intensities to advance the understanding of PCOS management and provide insight into the optimal exercise intensity for improved cardiometabolic outcomes. Secondary outcomes will include the impact of different exercise protocols on reproductive hormone profiles, mental health and health-related quality of life. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12615000242527. Registered on 17 March 2015