Dose-dependent effects of dietary nitrate on the oxygen cost of moderate-intensity exercise: Acute vs. chronic supplementation.

PURPOSE: To investigate whether chronic supplementation with a low or moderate dose of dietary nitrate (NO3(-)) reduces submaximal exercise oxygen uptake (V˙O2) and to assess whether or not this is dependent on acute NO3(-) administration prior to exercise. METHODS: Following baseline tests, 34 healthy subjects were allocated to receive 3 mmol NO3(-), 6 mmol NO3(-) or placebo. Two hours following the first ingestion, and after 7, 28 and 30 days of supplementation, subjects completed two moderate-intensity step exercise tests. On days 28 and 30, subjects in the NO3(-) groups completed the test 2 h post consumption of a NO3(-) dose (CHR + ACU) and a placebo dose (CHR). RESULTS: Plasma nitrite concentration ([NO2(-)]) was elevated in a dose-dependent manner at 2 h, 7 days and 28-30 days on the CHR + ACU visit. Compared to pre-treatment baseline, 6 mmol NO3(-) reduced the steady-state V˙O2 during moderate-intensity exercise by 3% at 2 h (P = 0.06), 7 days and at 28-30 days (both P < 0.05) on the CHR + ACU visit, but was unaffected by 3 mmol NO3(-) at all measurement points. On the CHR visit in the 6 mmol group, plasma [NO2(-)] had returned to pre-treatment baseline, but the steady-state V˙O2 remained reduced. CONCLUSION: Up to ∼4 weeks supplementation with 6 but not 3 mmol NO3(-) can reduce submaximal exercise V˙O2. A comparable reduction in submaximal exercise V˙O2 following chronic supplementation with 6 mmol NO3(-) can be achieved both with and without the acute ingestion of NO3(-) and associated elevation of plasma [NO2(-)].

No effect of acute L-arginine supplementation on O2 cost or exercise tolerance.

The extent to which dietary supplementation with the nitric oxide synthase (NOS) substrate, L-arginine (ARG), impacts on NO production and NO-mediated physiological responses is controversial. This randomised, double blinded, cross-over study investigated the effects of acute ARG supplementation on NO biomarkers, O2 cost of exercise and exercise tolerance in humans. In one experiment, 15 subjects completed moderate- and severe-intensity running bouts after acute supplementation with 6 g ARG or placebo (PLA). In another experiment, eight subjects completed moderate- and severe-intensity cycling bouts after acute supplementation with 6 g ARG plus 25 g of carbohydrate (ARG + CHO) or an energy-matched dose of carbohydrate alone (CHO). The plasma nitrite concentration was not different after ARG (Pre: 204 ± 79; Post: 241 ± 114 nM; P > 0.05) or ARG + CHO consumption (Pre: 304 ± 57; Post: 335 ± 116 nM; P > 0.05). During moderate-intensity exercise, the steady-state pulmonary VO2 was not different, relative to the respective placebo conditions, after ARG (PLA: 2,407 ± 318, ARG: 2,422 ± 333 mL min(-1)) or ARG + CHO (CHO: 1,695 ± 304, ARG + CHO: 1,712 ± 312 mL min(-1)) ingestion (P > 0.05). The tolerable duration of severe exercise was also not significantly different (P > 0.05) after ingesting ARG (PLA: 551 ± 140, ARG: 552 ± 150 s) or ARG + CHO (CHO: 457 ± 182, ARG + CHO: 441 ± 221 s). In conclusion, acute dietary supplementation with ARG or ARG + CHO did not alter biomarkers of NO synthesis, O2 cost of exercise or exercise tolerance in healthy subjects.

Dietary nitrate supplementation reduces the O2 cost of walking and running: a placebo-controlled study.

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.

Acute L-arginine supplementation reduces the O2 cost of moderate-intensity exercise and enhances high-intensity exercise tolerance.

It has recently been reported that dietary nitrate (NO(3)(-)) supplementation, which increases plasma nitrite (NO(2)(-)) concentration, a biomarker of nitric oxide (NO) availability, improves exercise efficiency and exercise tolerance in healthy humans. We hypothesized that dietary supplementation with L-arginine, the substrate for NO synthase (NOS), would elicit similar responses. In a double-blind, crossover study, nine healthy men (aged 19-38 yr) consumed 500 ml of a beverage containing 6 g of l-arginine (Arg) or a placebo beverage (PL) and completed a series of "step" moderate- and severe-intensity exercise bouts 1 h after ingestion of the beverage. Plasma NO(2)(-) concentration was significantly greater in the Arg than the PL group (331 ± 198 vs. 159 ± 102 nM, P < 0.05) and systolic blood pressure was significantly reduced (123 ± 3 vs. 131 ± 5 mmHg, P < 0.01). The steady-state O(2) uptake (VO(2)) during moderate-intensity exercise was reduced by 7% in the Arg group (1.48 ± 0.12 vs. 1.59 ± 0.14 l/min, P < 0.05). During severe-intensity exercise, the Vo(2) slow component amplitude was reduced (0.58 ± 0.23 and 0.76 ± 0.29 l/min in Arg and PL, respectively, P < 0.05) and the time to exhaustion was extended (707 ± 232 and 562 ± 145 s in Arg and PL, respectively, P < 0.05) following consumption of Arg. In conclusion, similar to the effects of increased dietary NO(3)(-) intake, elevating NO bioavailability through dietary L-Arg supplementation reduced the O(2) cost of moderate-intensity exercise and blunted the VO(2) slow component and extended the time to exhaustion during severe-intensity exercise.

Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans.

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 O2 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 +/- 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 +/- 44 vs. PL: 140 +/- 50 nM; P < 0.05), and systolic blood pressure was significantly reduced (BR: 124 +/- 2 vs. PL: 132 +/- 5 mmHg; P < 0.01). During moderate exercise, nitrate supplementation reduced muscle fractional O2 extraction (as estimated using near-infrared spectroscopy). The gain of the increase in pulmonary O2 uptake following the onset of moderate exercise was reduced by 19% in the BR condition (BR: 8.6 +/- 0.7 vs. PL: 10.8 +/- 1.6 ml.min(-1).W(-1); P < 0.05). During severe exercise, the O2 uptake slow component was reduced (BR: 0.57 +/- 0.20 vs. PL: 0.74 +/- 0.24 l/min; P < 0.05), and the time-to-exhaustion was extended (BR: 675 +/- 203 vs. PL: 583 +/- 145 s; P < 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.