Self-Expanding or Balloon-Expandable TAVR in Patients with a Small Aortic Annulus.

BACKGROUND: Patients with severe aortic stenosis and a small aortic annulus are at risk for impaired valvular hemodynamic performance and associated adverse cardiovascular clinical outcomes after transcatheter aortic-valve replacement (TAVR). METHODS: We randomly assigned patients with symptomatic severe aortic stenosis and an aortic-valve annulus area of 430 mm2 or less in a 1:1 ratio to undergo TAVR with either a self-expanding supraannular valve or a balloon-expandable valve. The coprimary end points, each assessed through 12 months, were a composite of death, disabling stroke, or rehospitalization for heart failure (tested for noninferiority) and a composite end point measuring bioprosthetic-valve dysfunction (tested for superiority). RESULTS: A total of 716 patients were treated at 83 sites in 13 countries (mean age, 80 years; 87% women; mean Society of Thoracic Surgeons Predicted Risk of Mortality, 3.3%). The Kaplan-Meier estimate of the percentage of patients who died, had a disabling stroke, or were rehospitalized for heart failure through 12 months was 9.4% with the self-expanding valve and 10.6% with the balloon-expandable valve (difference, -1.2 percentage points; 90% confidence interval [CI], -4.9 to 2.5; P<0.001 for noninferiority). The Kaplan-Meier estimate of the percentage of patients with bioprosthetic-valve dysfunction through 12 months was 9.4% with the self-expanding valve and 41.6% with the balloon-expandable valve (difference, -32.2 percentage points; 95% CI, -38.7 to -25.6; P<0.001 for superiority). The aortic-valve mean gradient at 12 months was 7.7 mm Hg with the self-expanding valve and 15.7 mm Hg with the balloon-expandable valve, and the corresponding values for additional secondary end points through 12 months were as follows: mean effective orifice area, 1.99 cm2 and 1.50 cm2; percentage of patients with hemodynamic structural valve dysfunction, 3.5% and 32.8%; and percentage of women with bioprosthetic-valve dysfunction, 10.2% and 43.3% (all P<0.001). Moderate or severe prosthesis-patient mismatch at 30 days was found in 11.2% of the patients in the self-expanding valve group and 35.3% of those in the balloon-expandable valve group (P<0.001). Major safety end points appeared to be similar in the two groups. CONCLUSIONS: Among patients with severe aortic stenosis and a small aortic annulus who underwent TAVR, a self-expanding supraannular valve was noninferior to a balloon-expandable valve with respect to clinical outcomes and was superior with respect to bioprosthetic-valve dysfunction through 12 months. (Funded by Medtronic; SMART ClinicalTrials.gov number, NCT04722250.).

Skeletal muscle mitochondrial correlates of critical power and W' in healthy active individuals.

The asymptote (critical power; CP) and curvature constant (W') of the hyperbolic power-duration relationship can predict performance within the severe-intensity exercise domain. However, the extent to which these parameters relate to skeletal muscle mitochondrial content and respiratory function is not known. Fifteen males (peak O2 uptake, 52.2 ± 8.7 mL kg-1 min-1; peak work rate, 366 ± 40 W; and gas exchange threshold, 162 ± 41 W) performed three to five constant-load tests to task failure for the determination of CP (246 ± 44 W) and W' (18.6 ± 4.1 kJ). Skeletal muscle biopsies were obtained from the vastus lateralis to determine citrate synthase (CS) activity, as a marker of mitochondrial content, and the ADP-stimulated respiration (P) and maximal electron transfer (E) through mitochondrial complexes (C) I-IV. The CP was positively correlated with CS activity (absolute CP, r = 0.881, P < 0.001; relative CP, r = 0.751, P = 0.001). The W' was not correlated with CS activity (P > 0.05). Relative CP was positively correlated with mass-corrected CI + IIE (r = 0.659, P = 0.038), with absolute CP being inversely correlated with CS activity-corrected CIVE (r = -0.701, P = 0.024). Relative W' was positively correlated with CS activity-corrected CI + IIP (r = 0.713, P = 0.021) and the phosphorylation control ratio (r = 0.661, P = 0.038). There were no further correlations between CP or W' and mitochondrial respiratory variables. These findings support the assertion that skeletal muscle mitochondrial oxidative capacity is positively associated with CP and that this relationship is strongly determined by mitochondrial content.

Nitrate ingestion blunts the increase in blood pressure during cool air exposure. A double-blind, placebo-controlled, randomized, crossover trial.

Cold exposure increases blood pressure (BP) and salivary flow rate (SFR). Increased cold-induced SFR would be hypothesised to enhance oral nitrate delivery for reduction to nitrite by oral anaerobes and to subsequently elevate plasma [nitrite] and nitric oxide bioavailability. We tested the hypothesis that dietary nitrate supplementation would increase plasma [nitrite] and lower BP to a greater extent in cool compared to normothermic conditions. Twelve males attended the laboratory on four occasions. Baseline measurements were completed at 28°C. Subsequently, participants ingested 140 mL of concentrated nitrate-rich (BR; ~13 mmol nitrate) or nitrate-depleted (PL) beetroot juice. Measurements were repeated over 3 h at either 28°C (Norm) or 20°C (Cool). Mean skin temperature was lowered compared to baseline in PL-Cool and BR-Cool. SFR was greater in BR-Norm, PL-Cool and BR-Cool than PL-Norm. Plasma [nitrite] at 3 h was higher in BR-Cool (592 ± 239 nM) vs. BR-Norm (410 ± 195 nM). Systolic BP (SBP) at 3 h was not different between PL-Norm (117 ± 6 mmHg) and BR-Norm (113 ± 9 mmHg). SBP increased above baseline at 1, 2 and 3 h in PL-Cool but not BR-Cool. These results suggest that BR consumption is more effective at increasing plasma [nitrite] in cool compared to normothermic conditions and blunts the rise in BP following acute cool air exposure, which might have implications for attenuating the increased cardiovascular strain in the cold.

Integrating molecular and clinical variables to predict myocardial recovery.

Mechanical unloading and circulatory support with left ventricular assist devices (LVADs) mediate significant myocardial improvement in a subset of advanced heart failure (HF) patients. The clinical and biological phenomena associated with cardiac recovery are under intensive investigation. Left ventricular (LV) apical tissue, alongside clinical data, were collected from HF patients at the time of LVAD implantation (n=208). RNA was isolated and mRNA transcripts were identified through RNA sequencing and confirmed with RT-qPCR. To our knowledge this is the first study to combine transcriptomic and clinical data to derive predictors of myocardial recovery. We used a bioinformatic approach to integrate 59 clinical variables and 22,373 mRNA transcripts at the time of LVAD implantation for the prediction of post-LVAD myocardial recovery defined as LV ejection fraction (LVEF) ≥40% and LV end-diastolic diameter (LVEDD) ≤5.9cm, as well as functional and structural LV improvement independently by using LVEF and LVEDD as continuous variables, respectively. To substantiate the predicted variables, we used a multi-model approach with logistic and linear regressions. Combining RNA and clinical data resulted in a gradient boosted model with 80 features achieving an AUC of 0.731±0.15 for predicting myocardial recovery. Variables associated with myocardial recovery from a clinical standpoint included HF duration, pre-LVAD LVEF, LVEDD, and HF pharmacologic therapy, and LRRN4CL (ligand binding and programmed cell death) from a biological standpoint. Our findings could have diagnostic, prognostic, and therapeutic implications for advanced HF patients, and inform the care of the broader HF population.

Post exercise hot water immersion and hot water immersion in isolation enhance vascular, blood marker, and perceptual responses when compared to exercise alone.

Exercise and passive heating induce some similar vascular hemodynamic, circulating blood marker, and perceptual responses. However, it remains unknown whether post exercise hot water immersion can synergise exercise derived responses and if they differ from hot water immersion alone. This study investigated the acute responses to post moderate-intensity exercise hot water immersion (EX+HWI) when compared to exercise (EX+REST) and hot water immersion (HWI+HWI) alone. Sixteen physically inactive middle-aged adults (nine males and seven females) completed a randomized cross-over counterbalanced design. Each condition consisted of two 30-min bouts separated by 10 min of rest. Cycling was set at a power output equivalent to 50% V̇o2 peak . Water temperature was controlled at 40°C up to the mid sternum with arms not submerged. Venous blood samples and artery ultrasound scans were assessed at 0 (baseline), 30 (immediately post stressor one), 70 (immediately post stressor two), and 100 min (recovery). Additional physiological and perceptual measures were assessed at 10-min intervals. Brachial and superficial femoral artery shear rates were higher after EX+HWI and HWI+HWI when compared with EX+REST (p < 0.001). Plasma nitrite was higher immediately following EX+HWI and HWI+HWI than EX+REST (p < 0.01). Serum interleukin-6 was higher immediately after EX+HWI compared to EX+REST (p = 0.046). Serum cortisol was lower at 30 min in the HWI+HWI condition in contrast to EX+REST (p = 0.026). EX+HWI and HWI+HWI were more enjoyable than EX+REST (p < 0.05). Irrespective of whether hot water immersion proceeded exercise or heating, hot water immersion enhanced vascular and blood marker responses, while also being more enjoyable than exercise alone.

Sleep architecture of elite soccer players surrounding match days as measured by WHOOP straps.

This study aimed to quantify and compare sleep architecture before and after home and away matches in elite soccer players from the English Premier League. Across two seasons, 6 male players (age 28 ± 5 y; body mass 85.1 ± 9.5 kg; height 1.86 ± 0.09 m) wore WHOOP straps to monitor sleep across 13 matches that kicked off before 17:00 h. For each, sleep was recorded the night before (MD-1), after (MD) and following the match (MD +1). Across these 3 days total sleep time (TST), sleep efficiency (SE), sleep disturbances, wake time, light sleep, deep sleep, REM sleep, sleep and wake onsets, alongside external load, were compared. TST was reduced after MD versus MD +1 (392.9 ± 76.4 vs 459.1 ± 66.7 min, p = 0.003) but no differences existed in any other sleep variables between days (p > 0.05). TST did not differ after home (386.9 ± 75.7 min) vs. away matches (401.0 ± 78.3 min) (p = 0.475), nor did other sleep variables (p > 0.05). GPS-derived external load peaked on MD (p < 0.05). In conclusion, despite reduced TST on MD, sleep architecture was unaffected after matches played before 17:00 h, suggesting sleep quality was not significantly compromised.

Combined effects of green tea supplementation and eccentric exercise on nuclear factor erythroid 2-related factor 2 activity.

PURPOSE: This study investigated whether combining eccentric exercise and green tea supplementation synergistically increased nuclear factor erythroid 2-related factor 2 (NRF2) activity, a transcription factor responsible for coordinating endogenous antioxidant expression. METHODS: In a double-blinded, randomized, between-subjects design, 24 males (mean [SD]; 23 [3] years, 179.6 [6.1] cm, 78.8 [10.6] kg) performed 100 drop jumps following a 6 days supplementation period with either green tea (poly)phenols (n = 12; 500 mg·d-1) or a placebo (n = 12; inulin). NRF2/antioxidant response element (ARE) binding in peripheral blood mononuclear cells (PBMCs), catalase (CAT) and glutathione reductase (GR) activity, 8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion, and differential leukocyte counts were measured pre-, post-, 1 h and 24 h post-exercise. RESULTS: Exercise did not increase NRF2/ARE binding (p = 0.12) (fold change vs rest: green tea = [post] 0.78 ± 0.45, [1 h] 1.17 ± 0.54, [24 h] 1.06 ± 0.56; placebo = [post] 1.40 ± 1.50, [1 h] 2.98 ± 3.70, [24 h] 1.04 ± 0.45). Furthermore, CAT activity (p = 0.12) and 8-OHdG excretion (p = 0.42) were unchanged in response to exercise and were not augmented by green tea supplementation (p > 0.05 for all). Exercise increased GR activity by 30% (p = 0.01), however no differences were found between supplement groups (p = 0.51). Leukocyte and neutrophil concentrations were only elevated post-exercise (p < 0.001 for all). CONCLUSION: Eccentric exercise, either performed alone or in conjunction with green tea supplementation, did not significantly increase NRF2 activity in PBMCs. TRIAL REGISTRATION NUMBER: osf.io/kz37g (registered: 15/09/21).

Influence of acute dietary nitrate supplementation timing on nitrate metabolism, central and peripheral blood pressure and exercise tolerance in young men.

PURPOSE: Dietary nitrate (NO3-) supplementation can lower systolic blood pressure (SBP) and improve exercise performance. Salivary flow rate (SFR) and pH are key determinants of oral NO3- reduction and purported to peak in the afternoon. We tested the hypotheses that NO3--rich beetroot juice (BR) would increase plasma [nitrite] ([NO2-]), lower SBP and improve exercise performance to a greater extent in the afternoon (AFT) compared to the morning (MORN) and evening (EVE). METHOD: Twelve males completed six experimental visits in a repeated-measures, crossover design. NO3--depleted beetroot juice (PL) or BR (~ 13 mmol NO3-) were ingested in the MORN, AFT and EVE. SFR and pH, salivary and plasma [NO3-] and [NO2-], brachial SBP and central SBP were measured pre and post supplementation. A severe-intensity exercise tolerance test was completed to determine cycling time to exhaustion (TTE). RESULTS: There were no between-condition differences in mean SFR or salivary pH. The elevation in plasma [NO2-] after BR ingestion was not different between BR-MORN, BR-AFT and BR-EVE. Brachial SBP was unchanged following BR supplementation in all conditions. Central SBP was reduced in BR-MORN (- 3 ± 4 mmHg), BR-AFT (- 4 ± 3 mmHg), and BR-EVE (- 2 ± 3 mmHg), with no differences between timepoints. TTE was not different between BR and PL at any timepoint. CONCLUSION: Acute BR supplementation was ineffective at improving TTE and brachial SBP and similarly effective at increasing plasma [NO2-] and lowering central SBP across the day, which may have implications for informing NO3- supplementation strategies.

Effects of Nutritional Interventions on Athletic Performance.

The search to comprehend the fundamental physiological factors that contribute to the exceptional endurance performance of elite human athletes is a long-standing endeavor within the field of sports science research [...].

Mechanically demanding eccentric exercise increases nuclear factor erythroid 2-related factor 2 activity in human peripheral blood mononuclear cells.

PRE-REGISTRATION NUMBER: osf.io/kz37g.

Cannabidiol Oil Ingested as Sublingual Drops or Within Gelatin Capsules Shows Similar Pharmacokinetic Profiles in Healthy Males.

Introduction: Cannabidiol (CBD) is a nonintoxicating phytocannabinoid used in clinical treatments and sold widely in consumer products. CBD products may be designed for sublingual or oral delivery, but it is unclear whether either is advantageous for CBD absorption. This study compared CBD pharmacokinetics after providing CBD oil as sublingual drops and within orally ingested gelatin capsules, at a dose relevant to consumer products. Materials and Methods: Eight males completed three conditions in a participant-blinded, randomized crossover design. Participants received the following combinations of placebo and CBD-containing (69 mg/mL) hemp oil in capsules and as sublingual drops: placebo capsules/placebo drops (Placebo), CBD capsules/placebo drops (CBD-Caps), and placebo capsules/CBD drops (CBD-Drops). Blood samples, blood pressure, and subjective scales were obtained/completed hourly for 6 h and at 24 h. Discussion: Plasma CBD concentrations were not different between CBD-Caps and CBD-Drops (interaction effect p=0.76). Peak CBD concentration (28.0±15.6 vs. 24.0±22.2 ng/mL), time of peak CBD concentration (4±1 vs. 4±2 h), and area under the concentration curve (45.3±20.3 vs. 41.8±23.3 ng/mL·6 h) were not different between conditions (p≥0.25). Cardiometabolic outcomes (plasma glucose/triacylglycerol, heart rate, blood pressure), liver function (plasma alanine aminotransferase/aspartate aminotransferase), kidney function (plasma creatinine), and subjective feelings/symptoms were not different between conditions (p≥0.07). Conclusions: Plasma CBD profiles were comparable between CBD-Caps and CBD-Drops, suggesting that there were not meaningful differences in routes of CBD absorption between conditions. This implies that CBD oil delivered sublingually is swallowed before oral mucosal CBD absorption occurs, which may have implications for research design, CBD product design, and consumer product choice.

Dietary nitrate ingested with and without pomegranate supplementation does not improve resistance exercise performance.

This study tested the hypothesis that co-ingesting nitrate (NO3-)-rich beetroot juice (BR) and pomegranate powder (POM) would enhance neuromuscular performance during vertical countermovement jumps, explosive kneeling countermovement push-ups, and back squats compared to BR ingestion alone. Fifteen recreationally-active males were assigned in a double-blind, randomized, crossover design, to supplement in 3 conditions: (1) NO3--depleted beetroot juice (PL; 0.10 mmol NO3-) with two empty gelatin capsules; (2) NO3--rich beetroot juice (BR; 11.8 mmol NO3-) with two empty gelatin capsules, and (3) BR with 1,000 mg of POM powder in two capsules (BR + POM). Participants completed 5 countermovement jumps and 5 kneeling countermovement push-ups interspersed by 1 min of recovery. Subsequently, participants performed 2 sets of 2 × 70% one-repetition maximum back squats, interspersed by 2 min of recovery. Plasma [NO3-] and nitrite ([NO2-]) were elevated following BR and BR + POM compared with PL and POM (p < 0.001) with no differences between BR and BR + POM (p > 0.05) or PL and POM (p > 0.05). Peak power during countermovement jumps increased by 3% following BR compared to BR + POM (88.50 ± 11.46 vs. 85.80 ± 10.14 W/Kg0.67, p = 0.009) but not PL (88.50 ± 11.46 vs. 85.58 ± 10.05 W/Kg0.67, p = 0.07). Neuromuscular performance was not different between conditions during explosive kneeling push-ups and back squats (p > 0.05). These data provide insight into the efficacy of NO3- to modulate explosive resistance exercise performance and indicate that supplementing with BR alone or combined with POM has limited ergogenic potential on resistance exercise. Furthermore, caution is required when combining BR with POM, as this could compromise aspects of resistance exercise performance, at least when compared to BR ingested independently.

Trimethylamine N-Oxide Concentration and Blood Pressure in Young Healthy Men and Women: A Replicated Crossover Study.

Trimethylamine N-oxide (TMAO), a gut-derived metabolite and marker of gut dysbiosis, has been linked to hypertension. Blood pressure is proposed to be elevated in hormonal contraceptive users and males compared to age-matched eumenorrheic females, but the extent to which TMAO differs between these populations has yet to be investigated. Peripheral and central blood pressure were measured, with the latter determined via applanation tonometry, and plasma TMAO concentration was assessed using liquid chromatography-tandem mass spectrometry. The following variables were assessed on two occasions in each of the following conditions: the early follicular phase (EFP) and mid-luteal phase (MLP) in eumenorrheic women (n = 13), and the pill-free interval (INACTIVE) and pill consumption days (ACTIVE) in women using oral contraceptive pills (n = 12), and in men (n = 22). Briefly, 17-ß-estradiol and progesterone concentrations were quantified via ELISA in all females. There were no differences in TMAO concentration between EFP (2.9 ± 1.7 µmol/L) and MLP (3.2 ± 1.1 µmol/L), between INACTIVE (3.3 ± 2.9 µmol/L) and ACTIVE (2.3 ± 1.1 µmol/L) days, or between men (3.0 ± 1.8 µmol/L), eumenorrheic women (3.0 ± 1.3 µmol/L) and contraceptive users (2.8 ± 1.4 µmol/L). Blood pressure was consistent across the menstrual cycle and pill days, but brachial systolic blood pressure was higher in males than females. There were no differences in brachial diastolic blood pressure or central blood pressure between the sexes. Repeated measures of TMAO, blood pressure, 17-ß-estradiol and progesterone were consistent in all populations. These findings suggest that the link between TMAO and blood pressure is limited in healthy young adults.

Effects of dietary nitrate supplementation on peak power output: Influence of supplementation strategy and population.

Increasing evidence indicates that dietary nitrate supplementation has the potential to increase muscular power output during skeletal muscle contractions. However, there is still a paucity of data characterizing the impact of different nitrate dosing regimens on nitric oxide bioavailability and its potential ergogenic effects across various population groups. This review discusses the potential influence of different dietary nitrate supplementation strategies on nitric oxide bioavailability and muscular peak power output in healthy adults, athletes, older adults and some clinical populations. Effect sizes were calculated for peak power output and absolute and/or relative nitrate doses were considered where applicable. There was no relationship between the effect sizes of peak power output change following nitrate supplementation and when nitrate dosage when considered in absolute or relative terms. Areas for further research are also recommended including a focus on nitrate dosing regimens that optimize nitric oxide bioavailability for enhancing peak power at times of increased muscular work in a variety of healthy and disease populations.

A comparison of advertised versus actual cannabidiol (CBD) content of oils, aqueous tinctures, e-liquids and drinks purchased in the UK.

BACKGROUND: Cannabidiol (CBD)-containing products are sold widely in consumer stores, but concerns have been raised regarding their quality, with notable discrepancies between advertised and actual CBD content. Information is limited regarding how different types of CBD products may differ in their deviation from advertised CBD concentrations. Therefore, CBD concentrations were quantified and compared in aqueous tinctures, oils, e-liquids and drinks. METHODS: Products (13 aqueous tinctures, 29 oils, 10 e-liquids and 11 drinks) were purchased online in the UK. CBD concentrations were quantified in aqueous tinctures, oils and e-liquids via high performance liquid chromatography (HPLC), and in drinks via gas chromatograhy-mass spectrometry (GC-MS). RESULTS: Measured concentrations fell -25.7 ± 17.3, -6.1 ± 7.8, -6.9 ± 4.6 and - 0.03 ± 0.06 mg/mL below advertised concentrations for aqueous tinctures, oils, e-liquids and drinks, respectively (medians ± interquartile ranges; p < .05). Oils deviated relatively less (-19.0 ± 14.5%) from advertised concentrations than e-liquids (-29.2 ± 10.2%), aqueous tinctures (-51.4 ± 41.4%) and drinks (-65.6 ± 36.5%; p < .01), whilst e-liquids deviated less than aqueous tinctures and drinks (p < .05), and deviation was not different between aqueous tinctures and drinks (p = .19). Only 5/63 (8%) products had measured concentrations within 10% of advertised concentrations. DISCUSSION: Similarly to previous studies, few products had measured CBD concentrations within 10% of advertised concentrations, with most falling below advertised concentrations. All individual product types deviated from advertised concentrations, with oils deviating least. These findings may be indicative of poor manufacturing standards, or that CBD undergoes degradation in consumer products. This reinforces concerns over quality of CBD-containing consumer products and may highlight the need for improved regulation of such products.

Effects of Dietary Nitrate Supplementation on Back Squat and Bench Press Performance: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis investigated the influence of dietary nitrate supplementation on resistance exercise performance according to the PRISMA guidelines. Searches were conducted on MEDLINE, PubMed, ScienceDirect, Scopus and SPORTDiscus databases up to April 2023. Inclusion criteria were adult resistance-trained males who supplemented with a nitrate-rich supplement and nitrate-deficient placebo to assess repetitions-to-failure (RTF), peak power, mean power, peak velocity, and/or mean velocity during back squat and bench press exercise. A random effects model was performed on six studies and showed that nitrate supplementation improved RTF (standardized mean difference [SMD]: 0.43, 95% confidence intervals [95% CI]: 0.156 to 0.699, p = 0.002), mean power (SMD: 0.40, 95% CI: 0.127 to 0.678, p = 0.004), and mean velocity (SMD: 0.57, 95% CI: 0.07 to 1.061, p = 0.025) but had no effect on peak power (SMD: 0.204, 95% CI: -0.004 to 0.411, p = 0.054) or peak velocity (SMD: 0.00, 95% CI: -0.173 to 0.173, p = 1.000) when back squat and bench press were combined. Subgroup analyses revealed that back squats were more likely to be enhanced and that a dosing regimen may influence the efficacy of nitrate supplementation. Overall, nitrate supplementation had a small beneficial effect on some aspects of resistance exercise performance, but there were limited studies available and the variability was large. Additional studies that focus on upper and lower body resistance exercise and nitrate dosage are required to elucidate the efficacy of dietary nitrate supplementation on resistance exercise performance.

Effects of Dietary Nitrate Supplementation on Performance during Single and Repeated Bouts of Short-Duration High-Intensity Exercise: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Inorganic nitrate (NO3-) has emerged as a potential ergogenic aid over the last couple of decades. While recent systematic reviews and meta-analyses have suggested some small positive effects of NO3- supplementation on performance across a range of exercise tasks, the effect of NO3- supplementation on performance during single and repeated bouts of short-duration, high-intensity exercise is unclear. This review was conducted following PRISMA guidelines. MEDLINE and SPORTDiscus were searched from inception to January 2023. A paired analysis model for cross-over trials was incorporated to perform a random effects meta-analysis for each performance outcome and to generate standardized mean differences (SMD) between the NO3- and placebo supplementation conditions. The systematic review and meta-analysis included 27 and 23 studies, respectively. Time to reach peak power (SMD: 0.75, p = 0.02), mean power output (SMD: 0.20, p = 0.02), and total distance covered in the Yo-Yo intermittent recovery level 1 test (SMD: 0.17, p < 0.0001) were all improved after NO3- supplementation. Dietary NO3- supplementation had small positive effects on some performance outcomes during single and repeated bouts of high-intensity exercise. Therefore, athletes competing in sports requiring single or repeated bouts of high-intensity exercise may benefit from NO3- supplementation.

Effects of dietary nitrate supplementation on muscular power output: Influence of supplementation strategy and population.

Increasing evidence indicates that dietary nitrate supplementation has the potential to increase muscular power output during skeletal muscle contractions. However, there is still a paucity of data characterizing the impact of different nitrate dosing regimens on nitric oxide bioavailability its potential ergogenic effects across various population groups. This narrative review discusses the potential influence of different dietary nitrate supplementation strategies on nitric oxide bioavailability and muscular power output in healthy adults, athletes, older adults and some clinical populations. Areas for further research are also recommended including a focus individualized nitrate dosing regimens to optimize nitric oxide bioavailability and to promote muscular power enhancements in different populations.

Dietary nitrate supplementation increases nitrate and nitrite concentrations in human skin interstitial fluid.

Acute dietary nitrate (NO3-) supplementation can increase [NO3-], but not nitrite ([NO2-]), in human skeletal muscle, though its effect on [NO3-] and [NO2-] in skin remains unknown. In an independent group design, 11 young adults ingested 140 mL of NO3--rich beetroot juice (BR; 9.6 mmol NO3-), and 6 young adults ingested 140 mL of a NO3--depleted placebo (PL). Skin dialysate, acquired through intradermal microdialysis, and venous blood samples were collected at baseline and every hour post-ingestion up to 4 h to assess dialysate and plasma [NO3-] and [NO2-]. The relative recovery rate of NO3- and NO2- through the microdialysis probe (73.1% and 62.8%), determined in a separate experiment, was used to estimate skin interstitial [NO3-] and [NO2-]. Baseline [NO3-] was lower, whereas baseline [NO2-] was higher in the skin interstitial fluid relative to plasma (both P < 0.001). Acute BR ingestion increased [NO3-] and [NO2-] in the skin interstitial fluid and plasma (all P < 0.001), with the magnitude being smaller in the skin interstitial fluid (e.g., 183 ± 54 vs. 491 ± 62 µM for Δ[NO3-] from baseline and 155 ± 190 vs. 217 ± 204 nM for Δ[NO2-] from baseline at 3 h post BR ingestion, both P ≤ 0.037). However, due to the aforementioned baseline differences, skin interstitial fluid [NO2-] post BR ingestion was higher, whereas [NO3-] was lower relative to plasma (all P < 0.001). These findings extend our understanding of NO3- and NO2- distribution at rest and indicate that acute BR supplementation increases [NO3-] and [NO2-] in human skin interstitial fluid.

Oral Temperature and pH Influence Dietary Nitrate Metabolism in Healthy Adults.

This study tested the hypothesis that the increases in salivary and plasma [NO2-] after dietary NO3- supplementation would be greater when oral temperature and pH were independently elevated, and increased further when oral temperature and pH were elevated concurrently. Seven healthy males (mean ± SD, age 23 ± 4 years) ingested 70 mL of beetroot juice concentrate (BR, which provided ~6.2 mmol NO3-) during six separate laboratory visits. In a randomised crossover experimental design, salivary and plasma [NO3-] and [NO2-] were assessed at a neutral oral pH with a low (TLo-pHNorm), intermediate (TMid-pHNorm), and high (THi-pHNorm) oral temperature, and when the oral pH was increased at a low (TLo-pHHi), intermediate (TMid-pHHi), and high (THi-pHHi) oral temperature. Compared with the TMid-pHNorm condition (976 ± 388 µM), the mean salivary [NO2-] 1-3 h post BR ingestion was higher in the TMid-pHHi (1855 ± 423 µM), THi-pHNorm (1371 ± 653 µM), THi-pHHi (1792 ± 741 µM), TLo-pHNorm (1495 ± 502 µM), and TLo-pHHi (2013 ± 662 µM) conditions, with salivary [NO2-] also higher at a given oral temperature when the oral pH was increased (p < 0.05). Plasma [NO2-] was higher 3 h post BR ingestion in the TMid-pHHi, THi-pHHi, and TLo-pHHi conditions, but not the TLo-pHNorm and THi-pHNorm conditions, compared with TMid-pHNorm (p < 0.05). Therefore, despite ingesting the same NO3- dose, the increases in salivary [NO2-] varied depending on the temperature and pH of the oral cavity, while the plasma [NO2-] increased independently of oral temperature, but to a greater extent at a higher oral pH.