Abstract

IntroductionNitrate supplementation in the form of beetroot juice (BRJ) ingestion has been shown to improve exercise tolerance during acute hypoxia, but its effect on exercise physiology remains unstudied during sustained terrestrial high altitude exposure. We hypothesized that performing exercise at high altitude would lower circulating nitrate and nitrite levels and that BRJ ingestion would reverse this phenomenon while concomitantly improving key determinants of aerobic exercise performance.MethodsTwenty seven healthy volunteers (21 male) underwent a series of exercise tests at sea level (SL, London, 75 m) and again after 5–8 days at high altitude (HA, Capanna Regina Margherita or “Margherita Hut,” 4,559 m). Using a double-blind protocol, participants were randomized to consume a beetroot/fruit juice beverage (three doses per day) with high levels of nitrate (∼0.18 mmol/kg/day) or a nitrate-depleted placebo (∼11.5 μmoles/kg/day) control drink, from 3 days prior to the exercise trials until completion. Submaximal constant work rate cycle tests were performed to determine exercise efficiency and a maximal incremental ramp exercise test was undertaken to measure aerobic capacity, using breath-by-breath pulmonary gas exchange measurements throughout. Concentrations of nitrate, nitrite and nitrosation products were quantified in plasma samples collected at 5 timepoints during the constant work rate tests. Linear mixed modeling was used to analyze data.ResultsAt both SL and HA, plasma nitrate concentrations were elevated in the nitrate supplementation group compared to placebo (P < 0.001) but did not change throughout increasing exercise work rate. Delta exercise efficiency was not altered by altitude exposure (P = 0.072) or nitrate supplementation (P = 0.836). V̇O2peak decreased by 24% at high altitude (P < 0.001) and was lower in the nitrate-supplemented group at both sea level and high altitude compared to placebo (P = 0.041). Dietary nitrate supplementation did not alter other peak exercise variables or oxygen consumption at anaerobic threshold. Circulating nitrite and S-nitrosothiol levels unexpectedly rose in a few individuals right after cessation of exercise at high altitude.ConclusionWhilst regularly consumed during an 8 days expedition to terrestrial high altitude, nitrate supplementation did not alter exercise efficiency and other exercise physiological variables, except decreasing V̇O2peak. These results and those of others question the practical utility of BRJ consumption during prolonged altitude exposure.

Highlights

  • Nitrate supplementation in the form of beetroot juice (BRJ) ingestion has been shown to improve exercise tolerance during acute hypoxia, but its effect on exercise physiology remains unstudied during sustained terrestrial high altitude exposure

  • Delta exercise efficiency was not altered by altitude exposure or by nitrate supplementation (Table 1)

  • V O2peak was lower following nitrate supplementation at SL and high altitude (HA) which supports some previous literature for hypoxic exposures at sea level (Kelly et al, 2014), but contradicts others (Arnold et al, 2015; Nybäck et al, 2017), though no interaction effect was present between altitude and nitrate supplementation

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Summary

Introduction

Nitrate supplementation in the form of beetroot juice (BRJ) ingestion has been shown to improve exercise tolerance during acute hypoxia, but its effect on exercise physiology remains unstudied during sustained terrestrial high altitude exposure. Nitric oxide (NO) is an important mediator of human physiological responses to hypoxia, because of its effects on pulmonary and cardiovascular function, erythropoiesis and metabolic regulation (Beall et al, 2012; Siervo et al, 2014; Luks et al, 2017; Murray et al, 2018) and due to its ability to match energy supply and demand at the cellular level (Umbrello et al, 2013) Consistent with these actions, high altitude natives have elevated plasma nitrate and nitrite concentrations (biomarkers of NO production) when compared to sea level controls (Erzurum et al, 2007), and lowlanders increase plasma concentrations of NO metabolites (nitrate, nitrite) and cyclic guanosine 3 ,5 -monophosphate (cGMP) during the acclimatization process (Janocha et al, 2011; Levett et al, 2011). A growing body of evidence, mostly obtained in studies conducted at SL, suggests that dietary nitrate supplementation, via the consumption of nitrate-rich beetroot or green leafy vegetables, could improve key physiological determinants of aerobic exercise performance to enhance hypoxic exercise tolerance

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