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.