AM. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol 107: 1144 -1155, 2009. First published August 6, 2009; doi:10.1152/japplphysiol.00722.2009.-Pharmacological sodium nitrate supplementation has been reported to reduce the O2 cost of submaximal exercise in humans. In this study, we hypothesized that dietary supplementation with inorganic nitrate in the form of beetroot juice (BR) would reduce the O 2 cost of submaximal exercise and enhance the tolerance to high-intensity exercise. In a double-blind, placebo (PL)-controlled, crossover study, eight men (aged 19 -38 yr) consumed 500 ml/day of either BR (containing 11.2 Ϯ 0.6 mM of nitrate) or blackcurrant cordial (as a PL, with negligible nitrate content) for 6 consecutive days and completed a series of "step" moderate-intensity and severe-intensity exercise tests on the last 3 days. On days 4 -6, plasma nitrite concentration was significantly greater following dietary nitrate supplementation compared with PL (BR: 273 Ϯ 44 vs. PL: 140 Ϯ 50 nM; P Ͻ 0.05), and systolic blood pressure was significantly reduced (BR: 124 Ϯ 2 vs. PL: 132 Ϯ 5 mmHg; P Ͻ 0.01). During moderate exercise, nitrate supplementation reduced muscle fractional O2 extraction (as estimated using nearinfrared spectroscopy). The gain of the increase in pulmonary O 2 uptake following the onset of moderate exercise was reduced by 19% in the BR condition (BR: 8.6 Ϯ 0.7 vs. PL: 10.8 Ϯ 1.6 ml ⅐ min Ϫ1 ⅐ W Ϫ1 ; P Ͻ 0.05). During severe exercise, the O 2 uptake slow component was reduced (BR: 0.57 Ϯ 0.20 vs. PL: 0.74 Ϯ 0.24 l/min; P Ͻ 0.05), and the time-to-exhaustion was extended (BR: 675 Ϯ 203 vs. PL: 583 Ϯ 145 s; P Ͻ 0.05). The reduced O2 cost of exercise following increased dietary nitrate intake has important implications for our understanding of the factors that regulate mitochondrial respiration and muscle contractile energetics in humans. exercise economy; muscle efficiency; O2 uptake; exercise performance; fatigue A FUNDAMENTAL TENET OF HUMAN exercise physiology is a predictable oxygen (O 2 ) cost for a given submaximal work rate. Upon the initiation of moderate-intensity exercise [i.e., exercise performed at work rates below the gas exchange threshold (GET)], pulmonary O 2 uptake (V O 2 ), which closely reflects O 2 consumption in the skeletal muscles (2, 29, 38), rises in an exponential fashion to attain a "steady state" within ϳ2-3 min in healthy humans (64). The steady-state increase in V O 2 is linearly related to the increase in external work rate; is essentially independent of factors such as age, health status or aerobic fitness; and approximates 10 ml O 2 ⅐min Ϫ1 ⅐W Ϫ1 of external power output during cycle ergometry (i.e., 10 ml ⅐min Ϫ1 ⅐W Ϫ1 ; Ref. 36). During supra-GET exercise, V O 2 dynamics become more complex, owing, in part, to the development of a delayed-onset V O 2 "slow component", which elevates the O 2 cost of exercise above 10 ml⅐min Ϫ1 ⅐W Ϫ1 (36, 64). Whereas it is known ...

The purpose of this study was to elucidate the mechanistic bases for the reported reduction in the O(2) cost of exercise following short-term dietary nitrate (NO(3)(-)) supplementation. In a randomized, double-blind, crossover study, seven men (aged 19-38 yr) consumed 500 ml/day of either nitrate-rich beet root juice (BR, 5.1 mmol of NO(3)(-)/day) or placebo (PL, with negligible nitrate content) for 6 consecutive days, and completed a series of low-intensity and high-intensity "step" exercise tests on the last 3 days for the determination of the muscle metabolic (using (31)P-MRS) and pulmonary oxygen uptake (Vo(2)) responses to exercise. On days 4-6, BR resulted in a significant increase in plasma [nitrite] (mean +/- SE, PL 231 +/- 76 vs. BR 547 +/- 55 nM; P < 0.05). During low-intensity exercise, BR attenuated the reduction in muscle phosphocreatine concentration ([PCr]; PL 8.1 +/- 1.2 vs. BR 5.2 +/- 0.8 mM; P < 0.05) and the increase in Vo(2) (PL 484 +/- 41 vs. BR 362 +/- 30 ml/min; P < 0.05). During high-intensity exercise, BR reduced the amplitudes of the [PCr] (PL 3.9 +/- 1.1 vs. BR 1.6 +/- 0.7 mM; P < 0.05) and Vo(2) (PL 209 +/- 30 vs. BR 100 +/- 26 ml/min; P < 0.05) slow components and improved time to exhaustion (PL 586 +/- 80 vs. BR 734 +/- 109 s; P < 0.01). The total ATP turnover rate was estimated to be less for both low-intensity (PL 296 +/- 58 vs. BR 192 +/- 38 microM/s; P < 0.05) and high-intensity (PL 607 +/- 65 vs. BR 436 +/- 43 microM/s; P < 0.05) exercise. Thus the reduced O(2) cost of exercise following dietary NO(3)(-) supplementation appears to be due to a reduced ATP cost of muscle force production. The reduced muscle metabolic perturbation with NO(3)(-) supplementation allowed high-intensity exercise to be tolerated for a greater period of time.

Dietary nitrate (NO(3)(-)) supplementation with beetroot juice (BR) over 4-6 days has been shown to reduce the O(2) cost of submaximal exercise and to improve exercise tolerance. However, it is not known whether shorter (or longer) periods of supplementation have similar (or greater) effects. We therefore investigated the effects of acute and chronic NO(3)(-) supplementation on resting blood pressure (BP) and the physiological responses to moderate-intensity exercise and ramp incremental cycle exercise in eight healthy subjects. Following baseline tests, the subjects were assigned in a balanced crossover design to receive BR (0.5 l/day; 5.2 mmol of NO(3)(-)/day) and placebo (PL; 0.5 l/day low-calorie juice cordial) treatments. The exercise protocol (two moderate-intensity step tests followed by a ramp test) was repeated 2.5 h following first ingestion (0.5 liter) and after 5 and 15 days of BR and PL. Plasma nitrite concentration (baseline: 454 ± 81 nM) was significantly elevated (+39% at 2.5 h postingestion; +25% at 5 days; +46% at 15 days; P < 0.05) and systolic and diastolic BP (baseline: 127 ± 6 and 72 ± 5 mmHg, respectively) were reduced by ∼4% throughout the BR supplementation period (P < 0.05). Compared with PL, the steady-state Vo(2) during moderate exercise was reduced by ∼4% after 2.5 h and remained similarly reduced after 5 and 15 days of BR (P < 0.05). The ramp test peak power and the work rate at the gas exchange threshold (baseline: 322 ± 67 W and 89 ± 15 W, respectively) were elevated after 15 days of BR (331 ± 68 W and 105 ± 28 W; P < 0.05) but not PL (323 ± 68 W and 84 ± 18 W). These results indicate that dietary NO(3)(-) supplementation acutely reduces BP and the O(2) cost of submaximal exercise and that these effects are maintained for at least 15 days if supplementation is continued.

We tested the hypothesis that the asymptote of the hyperbolic relationship between work rate and time to exhaustion during muscular exercise, the "critical power" (CP), represents the highest constant work rate that can be sustained without a progressive loss of homeostasis [as assessed using (31)P magnetic resonance spectroscopy (MRS) measurements of muscle metabolites]. Six healthy male subjects initially completed single-leg knee-extension exercise at three to four different constant work rates to the limit of tolerance (range 3-18 min) for estimation of the CP (mean +/- SD, 20 +/- 2 W). Subsequently, the subjects exercised at work rates 10% below CP (CP) for as long as possible, while the metabolic responses in the contracting quadriceps muscle, i.e., phosphorylcreatine concentration ([PCr]), P(i) concentration ([P(i)]), and pH, were estimated using (31)P-MRS. All subjects completed 20 min of CP exercise was 14.7 +/- 7.1 min. During CP exercise, however, [PCr] continued to fall to the point of exhaustion and [P(i)] and pH changed precipitously to values that are typically observed at the termination of high-intensity exhaustive exercise (end-exercise values = 26 +/- 16% of baseline [PCr], 564 +/- 167% of baseline [P(i)], and pH 6.87 +/- 0.10, all P < 0.05 vs.

Dietary supplementation with beetroot juice (BR) has been shown to reduce resting blood pressure and the O(2) cost of submaximal exercise and to increase tolerance to high-intensity cycling. We tested the hypothesis that the physiological effects of BR were consequent to its high NO(3)(-) content per se, and not the presence of other potentially bioactive compounds. We investigated changes in blood pressure, mitochondrial oxidative capacity (Q(max)), and physiological responses to walking and moderate- and severe-intensity running following dietary supplementation with BR and NO(3)(-)-depleted BR [placebo (PL)]. After control (nonsupplemented) tests, nine healthy, physically active male subjects were assigned in a randomized, double-blind, crossover design to receive BR (0.5 l/day, containing ∼6.2 mmol of NO(3)(-)) and PL (0.5 l/day, containing ∼0.003 mmol of NO(3)(-)) for 6 days. Subjects completed treadmill exercise tests on days 4 and 5 and knee-extension exercise tests for estimation of Q(max) (using (31)P-magnetic resonance spectroscopy) on day 6 of the supplementation periods. Relative to PL, BR elevated plasma NO(2)(-) concentration (183 ± 119 vs. 373 ± 211 nM, P < 0.05) and reduced systolic blood pressure (129 ± 9 vs. 124 ± 10 mmHg, P < 0.01). Q(max) was not different between PL and BR (0.93 ± 0.05 and 1.05 ± 0.22 mM/s, respectively). The O(2) cost of walking (0.87 ± 0.12 and 0.70 ± 0.10 l/min in PL and BR, respectively, P < 0.01), moderate-intensity running (2.26 ± 0.27 and 2.10 ± 0.28 l/min in PL and BR, respectively, P < 0.01), and severe-intensity running (end-exercise O(2) uptake = 3.77 ± 0.57 and 3.50 ± 0.62 l/min in PL and BL, respectively, P < 0.01) was reduced by BR, and time to exhaustion during severe-intensity running was increased by 15% (7.6 ± 1.5 and 8.7 ± 1.8 min in PL and BR, respectively, P < 0.01). In contrast, relative to control, PL supplementation did not alter plasma NO(2)(-) concentration, blood pressure, or the physiological responses to exercise. These results indicate that the positive effects of 6 days of BR supplementation on the physiological responses to exercise can be ascribed to the high NO(3)(-) content per se.

Severe-intensity constant-work-rate exercise results in the attainment of maximal oxygen uptake, but the muscle metabolic milieu at the limit of tolerance (T lim ) for such exercise remains to be elucidated. We hypothesized that T lim during severe-intensity exercise would be associated with the attainment of consistently low values of intramuscular phosphocreatine ([PCr]) and pH, as determined using 31 P magnetic resonance spectroscopy, irrespective of the work rate and the inspired O 2 fraction. We also hypothesized that hyperoxia would increase the asymptote of the hyperbolic power-duration relationship (the critical power, CP) without altering the curvature constant (W ). Seven subjects (mean ± s.d., age 30 ± 9 years) completed four constant-workrate knee-extension exercise bouts to the limit of tolerance (range, 3-10 min) both in normoxia (N) and in hyperoxia (H; 70% O 2 ) inside the bore of 1.5 T superconducting magnet. The [PCr] (∼5-10% of resting baseline) and pH (∼6.65) at the limit of tolerance during each of the four trials was not significantly different either in normoxia or in hyperoxia. At the same fixed work rate, the overall rate at which [PCr] fell with time was attenuated in hyperoxia (mean response time: N, 59 ± 20 versus H, 116 ± 46 s; P < 0.05). The CP was higher (N, 16.1 ± 2.6 versus H, 18.0 ± 2.3 W; P < 0.05) and the W was lower (N, 1.92 ± 0.70 versus H, 1.48 ± 0.31 kJ; P < 0.05) in hyperoxia compared with normoxia. These data indicate that T lim during severe-intensity exercise is associated with the attainment of consistently low values of muscle [PCr] and pH. The CP and W parameters of the power-duration relationship were both sensitive to the inspiration of hyperoxic gas.

It has been suggested that a prior bout of high-intensity exercise has the potential to enhance performance during subsequent high-intensity exercise by accelerating the O(2) uptake (Vo(2)) on-response. However, the optimal combination of prior exercise intensity and subsequent recovery duration required to elicit this effect is presently unclear. Eight male participants, aged 18-24 yr, completed step cycle ergometer exercise tests to 80% of the difference between the preestablished gas exchange threshold and maximal Vo(2) (i.e., 80%Delta) after no prior exercise (control) and after six different combinations of prior exercise intensity and recovery duration: 40%Delta with 3 min (40-3-80), 9 min (40-9-80), and 20 min (40-20-80) of recovery and 70%Delta with 3 min (70-3-80), 9 min (70-9-80), and 20 min (70-20-80) of recovery. Overall Vo(2) kinetics were accelerated relative to control in all conditions except for 40-9-80 and 40-20-80 conditions as a consequence of a reduction in the Vo(2) slow component amplitude; the phase II time constant was not significantly altered with any prior exercise/recovery combination. Exercise tolerance at 80%Delta was improved by 15% and 30% above control in the 70-9-80 and 70-20-80 conditions, respectively, but was impaired by 16% in the 70-3-80 condition. Prior exercise at 40%Delta did not significantly influence exercise tolerance regardless of the recovery duration. These data demonstrate that prior high-intensity exercise ( approximately 70%Delta) can enhance the tolerance to subsequent high-intensity exercise provided that it is coupled with adequate recovery duration (>or=9 min). This combination presumably optimizes the balance between preserving the effects of prior exercise on Vo(2) kinetics and providing sufficient time for muscle homeostasis (e.g., muscle phosphocreatine and H(+) concentrations) to be restored.

We hypothesized that a short-term training program involving repeated all-out sprint training (RST) would be more effective than work-matched, low-intensity endurance training (ET) in enhancing the kinetics of oxygen uptake (Vo(2)) and muscle deoxygenation {deoxyhemoglobin concentration ([HHb])} following the onset of exercise. Twenty-four recreationally active subjects (15 men, mean +/- SD: age 21 +/- 4 yr, height 173 +/- 9 cm, body mass 71 +/- 11 kg) were allocated to one of three groups: RST, which completed six sessions of four to seven 30-s RSTs; ET, which completed six sessions of work-matched, moderate-intensity cycling; and a control group (CON). All subjects completed moderate-intensity and severe-intensity "step" exercise transitions before (Pre) and after the 2-wk intervention period (Post). Following RST, [HHb] kinetics were speeded, and the amplitude of the [HHb] response was increased during both moderate and severe exercise (P < 0.05); the phase II Vo(2) kinetics were accelerated for both moderate (Pre: 28 +/- 8, Post: 21 +/- 8 s; P < 0.01) and severe (Pre: 29 +/- 5, Post: 23 +/- 5 s; P < 0.05) exercise; the amplitude of the Vo(2) slow component was reduced (Pre: 0.52 +/- 0.19, Post: 0.40 +/- 0.17 l/min; P < 0.01); and exercise tolerance during severe exercise was improved by 53% (Pre: 700 +/- 234, Post: 1,074 +/- 431 s; P < 0.01). None of these parameters was significantly altered in the ET and CON groups. Six sessions of RST, but not ET, resulted in changes in [HHb] kinetics consistent with enhanced fractional muscle O(2) extraction, faster Vo(2) kinetics, and an increased tolerance to high-intensity exercise.