Inorganic nitrate supplementation improves muscle oxygenation, O₂uptake kinetics, and exercise tolerance at high but not low pedal rates

Abstract

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...

Dietary nitrate supplementation enhances short but not longer duration running time-trial performance

“…It is therefore possible that elevated type II muscle Ca 2+ handling and muscle contractile function may have further contributed to the improved 1500 m performance observed in the present investigation. Furthermore, several recent studies have observed improvements in physiological functioning and exercise performance in situations where type II muscle recruitment is likely to be high (Breese et al 2013;Bailey et al 2015;Coggan et al 2015), which further supports the findings of this investigation.…”

“…Recent data from murine models suggest that NO 3 − supplementation elevates blood flow and oxygenation (Ferguson et al 2013(Ferguson et al , 2015, and increases calcium (Ca 2+ ) handling protein expression and force production (Hernandez et al 2012) in type II muscle only (for review, see Jones et al 2016). Therefore, the beneficial effects of NO 3 − supplementation might be restricted to, or most pronounced during, exercise where type II fibers are predominantly recruited (Breese et al 2013;Bailey et al 2015;Coggan et al 2015), such as during short duration exercise where a higher relative work rate can be adopted (Essén 1978;Sale 1987). Additionally, hypoxia and acidosis-cellular conditions particularly prevalent at higher work rates (Richardson et al 1995;Robergs et al 2004)-are known to enhance the reduction of NO 2 − into NO (Modin et al 2001;Cosby et al 2003;Castello et al 2006).…”

Dietary nitrate supplementation enhances high-intensity running performance in moderate normobaric hypoxia, independent of aerobic fitness

“…Further, there is evidence from murine model investigations that nitrate supplementation may enhance tissue blood flow [41,42] and muscle contractile function [9] preferentially in type II muscle fibres. It is therefore possible that nitrate supplementation is more effective during shorter more high-intensity exercise, during which these muscle fibres are more heavily recruited [9,[43][44][45]64], or else in individuals with greater distribution of type II muscle fibres [43]. The time-trial duration employed in this study (< 6 minutes) was considerably less than other investigations (~ 17 -48 minutes) which have not observed an ergogenic effect of nitrate supplementation in hypoxia [38][39][40], and may be important.…”

“…Moreover, nitrate supplementation has been demonstrated to elicit beneficial effects when the contribution of type II muscle towards force generation is high, including at fast but not slow muscle contraction frequencies [44], and during the transition from moderate to severe but not unloaded to moderate intensity exercise [45].…”

Medium-term effects of dietary nitrate supplementation on systolic and diastolic blood pressure in adults

“…Participant characteristics: Five studies recruited young, non-smoking, healthy 135 participants [7,21,23,25,26], three studies were conducted in older healthy subjects [17,19,27],…”