Ϫ ] increased in a dose-dependent manner, with the peak changes occurring at approximately 2-3 h. Compared with PL, 70 ml BR did not alter the physiological responses to exercise. However, 140 and 280 ml BR reduced the steady-state oxygen (O2) uptake during moderateintensity exercise by 1.7% (P ϭ 0.06) and 3.0% (P Ͻ 0.05), whereas time-to-task failure was extended by 14% and 12% (both P Ͻ 0.05), respectively, compared with PL. The results indicate that whereas plasma [NO 2 Ϫ ] and the O2 cost of moderate-intensity exercise are altered dose dependently with NO 3 Ϫ -rich BR, there is no additional improvement in exercise tolerance after ingesting BR containing 16.8 compared with 8.4 mmol NO 3 Ϫ . These findings have important implications for the use of BR to enhance cardiovascular health and exercise performance in young adults.nitrate; nitrite; nitric oxide; blood pressure; exercise economy; O2 uptake; exercise tolerance NITRIC OXIDE (NO) IS A GASEOUS signaling molecule that modulates human physiological function via its role in, for example, the regulation of blood flow, neurotransmission, immune function, glucose and calcium homeostasis, muscle contractility, and mitochondrial respiration (9, 36). 1 NO is generated through the oxidation of the amino acid L-arginine Ϫ ] peaked 3 h postingestion, remained close to peak values until 5 h postingestion, and returned to baseline after 24 h (39). The systolic and diastolic BP and the mean arterial pressure (MAP) were reduced significantly, by ϳ10, ϳ8, and ϳ8 mmHg, respectively, at 2.5-3 h after BR intake. The same research group later reported a dose-dependent increase in plasma [ ] was accompanied by significant reductions in both systolic BP (of ϳ2, ϳ6, and ϳ9 mmHg, respectively) and diastolic BP (of ϳ4, ϳ4, and ϳ6 mmHg, respectively). However, since BR contains polyphenols and antioxidants, which can facilitate the synthesis of NO from NO 2 Ϫ in the stomach (30), it is unclear whether BP is similarly impacted when different doses of BR are ingested compared with equivalent doses of NO 3 Ϫ salts. Given the growing interest in dietary NO 3 Ϫ supplementation in the form of BR amongst athletes and the general population, it is important to determine the pharmacokinetic-pharmacodynamic relationship between different volumes of BR consumption and changes in plasma [NO 2 Ϫ ] and BP to establish an optimal dose for beneficial effects.Recent investigations suggest that dietary NO 3 Ϫ supplementation has the potential to influence human physiology beyond 1 This article is the topic of an Invited Editorial by L. Burke (5a).

The gas exchange threshold and the critical power demarcate discrete exercise intensity domains. For the first time, we show that the limit of tolerance during whole body exercise within these domains is characterized by distinct metabolic and neuromuscular responses. Fatigue development during exercise greater than critical power is associated with the attainment of consistent “limiting” values of muscle metabolites, whereas substrate availability and limitations to muscle activation may constrain performance at lower intensities.

Recent studies have suggested that dietary inorganic nitrate (NO₃(-)) supplementation may improve muscle efficiency and endurance exercise tolerance but possible effects during team sport-specific intense intermittent exercise have not been examined. We hypothesized that NO₃(-) supplementation would enhance high-intensity intermittent exercise performance. Fourteen male recreational team-sport players were assigned in a double-blind, randomized, crossover design to consume 490 mL of concentrated, nitrate-rich beetroot juice (BR) and nitrate-depleted placebo juice (PL) over ~30 h preceding the completion of a Yo-Yo intermittent recovery level 1 test (Yo-Yo IR1). Resting plasma nitrite concentration ([NO₂(-)]) was ~400% greater in BR compared to PL. Plasma [NO₂(-)] declined by 20% in PL (P < 0.05) and by 54 % in BR (P < 0.05) from pre-exercise to end-exercise. Performance in the Yo-Yo IR1 was 4.2% greater (P < 0.05) with BR (1,704 ± 304 m) compared to PL (1,636 ± 288 m). Blood [lactate] was not different between BR and PL, but the mean blood [glucose] was lower (3.8 ± 0.8 vs. 4.2 ± 1.1 mM, P < 0.05) and the rise in plasma [K(+)] tended to be reduced in BR compared to PL (P = 0.08). These findings suggest that NO₃(-) supplementation may promote NO production via the nitrate-nitrite-NO pathway and enhance Yo-Yo IR1 test performance, perhaps by facilitating greater muscle glucose uptake or by better maintaining muscle excitability. Dietary NO₃(-) supplementation improves performance during intense intermittent exercise and may be a useful ergogenic aid for team sports players.

Key pointsr The power-asymptote (critical power; CP) of the hyperbolic power-time relationship for high-intensity exercise defines a threshold between steady-state and non-steady-state exercise intensities and the curvature constant (W ) indicates a fixed capacity for work >CP that is related to a loss of muscular efficiency.r The present study reports novel evidence on the muscle metabolic underpinnings of CP and W during whole-body exercise and their relationships to muscle fibre type.r We show that the W is not correlated with muscle fibre type distribution and that it represents an elevated energy contribution from both oxidative and glycolytic/glycogenolytic metabolism.r We show that there is a positive correlation between CP and highly oxidative type I muscle fibres and that muscle metabolic steady-state is attainable CP.r Our findings indicate a mechanistic link between the bioenergetic characteristics of muscle fibre types and the power-time relationship for high-intensity exercise.Abstract We hypothesized that: (1) the critical power (CP) will represent a boundary separating steady-state from non-steady-state muscle metabolic responses during whole-body exercise and (2) that the CP and the curvature constant (W ) of the power-time relationship for high-intensity exercise will be correlated with type I and type IIx muscle fibre distributions, respectively. Four men and four women performed a 3 min all-out cycling test for the estimation of CP and constant work rate (CWR) tests slightly >CP until exhaustion (T lim ), slightly CP T lim isotime to test the first hypothesis. Eleven men performed 3 min all-out tests and donated muscle biopsies to test the second hypothesis. Below CP, muscle [PCr] [42.6 ± 7.1 vs. 49.4 ± 6.9 mmol (kg d.w.) −1 ], [La − ] [34.8 ± 12.6 vs. 35.5 ± 13.2 mmol (kg d.w.) −1 ] and pH (7.11 ± 0.08 vs. 7.10 ± 0.11) remained stable between ß12 and 24 min (P > 0.05 for all), whereas these variables changed with time >CP such that they were greater [[La − ] 95.6 ± 14.1 mmol (kg d.w.) −1 ] and lower [[PCr] 24.2 ± 3.9 mmol (kg d.w.) −1 ; pH 6.84 ± 0.06] (P < 0.05) at T lim (740 ± 186 s) than during the

Nitric oxide (NO) plays a plethora of important roles in the human body. Insufficient production of NO (for example, during older age and in various disease conditions) can adversely impact health and physical performance. In addition to its endogenous production through the oxidation of l-arginine, NO can be formed nonenzymatically via the reduction of nitrate and nitrite, and the storage of these anions can be augmented by the consumption of nitrate-rich foodstuffs such as green leafy vegetables. Recent studies indicate that dietary nitrate supplementation, administered most commonly in the form of beetroot juice, can ( a) improve muscle efficiency by reducing the O cost of submaximal exercise and thereby improve endurance exercise performance and ( b) enhance skeletal muscle contractile function and thereby improve muscle power and sprint exercise performance. This review describes the physiological mechanisms potentially responsible for these effects, outlines the circumstances in which ergogenic effects are most likely to be evident, and discusses the effects of dietary nitrate supplementation on physical performance in a range of human populations.

Ϫ ]), oxygen uptake (V O2) kinetics, and exercise tolerance in normoxia (N) and hypoxia (H). In a doubleblind, crossover study, 12 healthy subjects completed cycle exercise tests, twice in N (20.9% O2) and twice in H (13.1% O2). Subjects ingested either 140 ml/day of NO 3 Ϫ -rich beetroot juice (8.4 mmol NO3; BR) or NO 3 Ϫ -depleted beetroot juice (PL) for 3 days prior to moderate-intensity and severe-intensity exercise tests in H and N. Preexercise plasma [NO 2 Ϫ ] was significantly elevated in H-BR and N-BR compared with H-PL (P Ͻ 0.01) and N-PL (P Ͻ 0.01). The rate of decline in plasma [NO 2 Ϫ ] was greater during severe-intensity exercise in H-BR [Ϫ30 Ϯ 22 nM/min, 95% confidence interval (CI); Ϫ44, Ϫ16] compared with H-PL (Ϫ7 Ϯ 10 nM/min, 95% CI; Ϫ13, Ϫ1; P Ͻ 0.01) and in N-BR (Ϫ26 Ϯ 19 nM/min, 95% CI; Ϫ38, Ϫ14) compared with N-PL (Ϫ1 Ϯ 6 nM/min, 95% CI; Ϫ5, 2; P Ͻ 0.01). During moderate-intensity exercise, steady-state pulmonary V O2 was lower in H-BR (1.91 Ϯ 0.28 l/min, 95% CI; 1.77, 2.13) compared with H-PL (2.05 Ϯ 0.25 l/min, 95% CI; 1.93, 2.26; P ϭ 0.02), and V O2 kinetics was faster in H-BR (: 24 Ϯ 13 s, 95% CI; 15, 32) compared with H-PL (31 Ϯ 11 s, 95% CI; 23, 38; P ϭ 0.04). NO 3 Ϫ supplementation had no significant effect on V O2 kinetics during severe-intensity exercise in hypoxia, or during moderate-intensity or severe-intensity exercise in normoxia. Tolerance to severe-intensity exercise was improved by NO 3 Ϫ in hypoxia (H-PL: 197 Ϯ 28; 95% CI; 173, 220 vs. H-BR: 214 Ϯ 43 s, 95% CI; 177, 249; P ϭ 0.04) but not normoxia. The metabolism of NO 2 Ϫ during exercise is altered by NO 3 Ϫ supplementation, exercise, and to a lesser extent, hypoxia. In hypoxia, NO 3 Ϫ supplementation enhances V O 2 kinetics during moderate-intensity exercise and improves severe-intensity exercise tolerance. These findings may have important implications for individuals exercising at altitude. hypoxia; beetroot juice; nitric oxide; efficiency; performance NITRIC OXIDE (NO) IS A UBIQUITOUS, water-soluble, free radical gas that plays a crucial role in many biological processes. Effective NO production is important in normal physiological functioning, from the regulation of blood flow, muscle contractility, and mitochondrial respiration to host defense, neurotransmission, and glucose and calcium homeostasis (11,17,60). NO production via the oxidation of L-arginine, in a process catalyzed by nitric oxide synthase (NOS), may be blunted in conditions of reduced O 2 availability (52). It is now widely accepted that NO can also be generated via an alternative pathway, whereby inorganic nitrate (NO 3 Ϫ ) is reduced to nitrite (NO 2 Ϫ ) and further to NO. This NOS-and O 2 -independent NO 3 Ϫ -NO 2 Ϫ -NO pathway represents a complementary system for NO synthesis spanning a broad range of redox states (49). In addition to being produced endogenously, the body's NO 3 Ϫ stores can be increased via the diet, with green leafy vegetables and beetroot being particularly rich in NO 3 Ϫ . Upon ingestion, inorganic NO 3 Ϫ is absorbed from the ...

These findings suggest that dietary NO3 (-) enhances repeated sprint performance and may attenuate the decline in cognitive function (and specifically reaction time) that may occur during prolonged intermittent exercise.

Bailey SJ, Varnham RL, DiMenna FJ, Breese BC, Wylie LJ, Jones AM. Inorganic nitrate supplementation improves muscle oxygenation, O2 uptake kinetics, and exercise tolerance at high but not low pedal rates. J Appl Physiol 118: 1396 -1405, 2015. First published April 9, 2015 doi:10.1152/japplphysiol.01141.2014.-We tested the hypothesis that inorganic nitrate (NO3 Ϫ ) supplementation would improve muscle oxygenation, pulmonary oxygen uptake (V O2) kinetics, and exercise tolerance (Tlim) to a greater extent when cycling at high compared with low pedal rates. In a randomized, placebo-controlled cross-over study, seven subjects (mean Ϯ SD, age 21 Ϯ 2 yr, body mass 86 Ϯ 10 kg) completed severe-intensity step cycle tests at pedal cadences of 35 rpm and 115 rpm during separate nine-day supplementation periods with NO3 Ϫ -rich beetroot juice (BR) (providing 8.4 mmol NO3 Ϫ /day) and placebo (PLA). Compared with PLA, plasma nitrite concentration increased 178% with BR (P Ͻ 0.01). There were no significant differences in muscle oxyhemoglobin concentration ([O2Hb]), phase II V O2 kinetics, or Tlim between BR and PLA when cycling at 35 rpm (P Ͼ 0.05). However, when cycling at 115 rpm, muscle [O2Hb] was higher at baseline and throughout exercise, phase II V O2 kinetics was faster (47 Ϯ 16 s vs. 61 Ϯ 25 s; P Ͻ 0.05), and Tlim was greater (362 Ϯ 137 s vs. 297 Ϯ 79 s; P Ͻ 0.05) with BR compared with PLA. These results suggest that short-term BR supplementation can increase muscle oxygenation, expedite the adjustment of oxidative metabolism, and enhance exercise tolerance when cycling at a high, but not a low, pedal cadence in healthy recreationally active subjects. These findings support recent observations that NO3 Ϫ supplementation may be particularly effective at improving physiological and functional responses in type II muscle fibers. nitric oxide; vascular function; oxidative metabolism; exercise performance; fatigue NITRIC OXIDE (NO) IS A DIFFUSIBLE GAS that impacts a plethora of physiological responses including skeletal muscle perfusion, metabolism, force production, and fatigue resistance (56). It is well documented that NO is produced by the nitric oxide synthase enzymes, which catalyze the complex five-electron oxidation of the semiessential amino acid, L-arginine (10). More recently, there has been a growing appreciation of the potential for NO synthesis from the simple one-electron reduction of nitrite (NO 2 Ϫ ), in a reaction catalyzed by numerous NO 2 Ϫ reductases (44, 57). Importantly, increasing the intake of dietary inorganic nitrate (NO 3 Ϫ ), which passes into the enterosalivary circulation for subsequent reduction to NO 2 Ϫ by oral anaerobes (19), has been shown to positively impact NO biomarkers, exercise efficiency, and exercise tolerance in recreationally active subjects (3,4,12,42,43,58,61). Therefore, supplementation with NO 3 Ϫ appears to represent an effective dietary intervention to improve NO bioavailability, contractile efficiency, and fatigue resistance.Results from in vitro studies suggest that th...