1932

Abstract

Nitric oxide (NO) plays a plethora of important roles in the human body. Insufficient production of NO (for example, during older age and in various disease conditions) can adversely impact health and physical performance. In addition to its endogenous production through the oxidation of -arginine, NO can be formed nonenzymatically via the reduction of nitrate and nitrite, and the storage of these anions can be augmented by the consumption of nitrate-rich foodstuffs such as green leafy vegetables. Recent studies indicate that dietary nitrate supplementation, administered most commonly in the form of beetroot juice, can () improve muscle efficiency by reducing the O cost of submaximal exercise and thereby improve endurance exercise performance and () enhance skeletal muscle contractile function and thereby improve muscle power and sprint exercise performance. This review describes the physiological mechanisms potentially responsible for these effects, outlines the circumstances in which ergogenic effects are most likely to be evident, and discusses the effects of dietary nitrate supplementation on physical performance in a range of human populations.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-nutr-082117-051622
2018-08-21
2024-07-19
Loading full text...

Full text loading...

/deliver/fulltext/nutr/38/1/annurev-nutr-082117-051622.html?itemId=/content/journals/10.1146/annurev-nutr-082117-051622&mimeType=html&fmt=ahah

Literature Cited

  1. 1.  Aamand R, Dalsgaard T, Ho YC, Moller A, Roepstorff A, Lund TE 2013. A NO way to BOLD? Dietary nitrate alters the hemodynamic response to visual stimulation. Neuroimage 83:397–407
    [Google Scholar]
  2. 2.  Adachi H, Nguyen PH, Belardinelli R, Hunter D, Jung T, Wasserman K 1997. Nitric oxide production during exercise in chronic heart failure. Am. Heart J. 134:196–202
    [Google Scholar]
  3. 3.  Allen DG, Lamb GD, Westerblad H 2008. Skeletal muscle fatigue: cellular mechanisms. Physiol. Rev. 88:287–332
    [Google Scholar]
  4. 4.  Alveres TS, Conte-Junior CA, Silva JT, Paschoalin VM 2012. Acute L-arginine supplementation does not increase nitric oxide production in healthy subjects. Nutr. Metab. 9:54
    [Google Scholar]
  5. 5.  Arnold JT, Oliver SJ, Lewis-Jones TM, Wylie LJ, Macdonald JH 2015. Beetroot juice does not enhance altitude running performance in well-trained athletes. Appl. Physiol. Nutr. Metab. 40:6590–95
    [Google Scholar]
  6. 6.  Aucouturier J, Boissière J, Pawlak-Chaouch M, Cuvelier G, Gamelin FX 2015. Effect of dietary nitrate supplementation on tolerance to supramaximal intensity intermittent exercise. Nitric Oxide 49:16–25
    [Google Scholar]
  7. 7.  Bailey SJ, Blackwell JR, Lord T, Vanhatalo A, Winyard PG 2015. L-citrulline supplementation improved O2 uptake kinetics and high-intensity exercise performance in humans. J. Appl. Physiol. 119:385–95
    [Google Scholar]
  8. 8.  Bailey SJ, Fulford J, Vanhatalo A, Winyard P, Blackwell JR et al. 2010. Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans. J. Appl. Physiol. 109:135–48
    [Google Scholar]
  9. 9.  Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, Dimenna FJ et al. 2009. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J. Appl. Physiol. 107:1144–55
    [Google Scholar]
  10. 10.  Bangsbo J, Iaia FM, Krustrup P 2008. The Yo-Yo intermittent recovery test: a useful tool for evaluation of physical performance in intermittent sports. Sports Med 38:37–51
    [Google Scholar]
  11. 11.  Benjamin N, O'Driscoll F, Dougall H, Duncan F, Smith L et al. 1994. Stomach NO synthesis. Nature 368:502
    [Google Scholar]
  12. 12.  Berry MJ, Justus NW, Hauser JI, Case AH, Helms CC et al. 2015. Dietary nitrate supplementation improves exercise performance and decreases blood pressure in COPD patients. Nitric Oxide 48:22–30
    [Google Scholar]
  13. 13.  Bescós R, Ferrer-Roca V, Galilea PA, Roig A, Drobnic F et al. 2012. Sodium nitrate supplementation does not enhance performance of endurance athletes. Med. Sci. Sports Exerc. 44:2400–9
    [Google Scholar]
  14. 14.  Bond H, Morton L, Braakhuis AJ 2012. Dietary nitrate supplementation improves rowing performance in well-trained rowers. Int. J. Sport Nutr. Exerc. Metab. 22:4251–56
    [Google Scholar]
  15. 15.  Boorsma RK, Whitfield J, Spriet LL 2014. Beetroot juice supplementation does not improve performance of elite 1500-m runners. Med. Sci. Sports Exerc. 46:2326–34
    [Google Scholar]
  16. 16.  Bourdillon N, Fan JL, Uva B, Müller H, Meyer P, Kayser B 2015. Effect of oral nitrate supplementation on pulmonary hemodynamics during exercise and time trial performance in normoxia and hypoxia: a randomized controlled trial. Front. Physiol. 6:288
    [Google Scholar]
  17. 17.  Bredt DS 1999. Endogenous nitric oxide synthesis: biological functions and pathophysiology. Free Radic. Res. 31:577–96
    [Google Scholar]
  18. 18.  Brown GC, Cooper CE 1994. Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett 356:295–98
    [Google Scholar]
  19. 19.  Bryan NS, Ivy JL 2015. Inorganic nitrite and nitrate: evidence to support consideration as dietary nutrients. Nutr. Res. 35:8643–54
    [Google Scholar]
  20. 20.  Callahan MJ, Parr EB, Hawley JA, Burke LM 2016. Single and combined effects of beetroot crystals and sodium bicarbonate on 4-km cycling time trial performance. Int. J. Sport Nutr. Exerc. Metab. 27:271–78
    [Google Scholar]
  21. 21.  Casey DP, Treichler DP, Ganger CT4th, Schneider AC, Ueda K 2015. Acute dietary nitrate supplementation enhances compensatory vasodilation during hypoxic exercise in older adults. J. Appl. Physiol. 118:2178–86
    [Google Scholar]
  22. 22.  Castello PR, David PS, McClure T, Crook Z, Poyton RO 2006. Mitochondrial cytochrome oxidase produces nitric oxide under hypoxic conditions: implications for oxygen sensing and hypoxic signaling in eukaryotes. Cell Metab 3:277–87
    [Google Scholar]
  23. 23.  Cermak NM, Gibala MJ, van Loon LJ 2012.a Nitrate supplementation's improvement of 10-km time-trial performance in trained cyclists. Int. J. Sport Nutr. Exerc. Metab. 22:64–71
    [Google Scholar]
  24. 24.  Cermak NM, Res P, Stinkens R, Lundberg JO, Gibala MJ et al. 2012.b No improvement in endurance performance after a single dose of beetroot juice. Int. J. Sport Nutr. Exerc. Metab. 22:470–78
    [Google Scholar]
  25. 25.  Chance B, Williams GR 1955. Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization. J. Biol. Chem. 217:383–93
    [Google Scholar]
  26. 26.  Christensen PM, Nyberg M, Bangsbo J 2013. Influence of nitrate supplementation on VO2 kinetics and endurance of elite cyclists. Scand. J. Med. Sci. Sports 23:1e21–31
    [Google Scholar]
  27. 27.  Coffey VG, Hawley JA 2007. The molecular bases of training adaptation. Sports Med 37:9737–63
    [Google Scholar]
  28. 28.  Coggan AR, Leibowitz JL, Kadkhodayan A, Thomas DP, Ramamurthy S et al. 2015. Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women. Nitric Oxide 1:4816–21
    [Google Scholar]
  29. 29.  Colcombe SJ, Erickson KI, Scalf PE, Kim JS, Prakash R et al. 2006. Aerobic exercise training increases brain volume in aging humans. J. Gerontol. A Biol. Sci. Med. Sci. 61:111166–70
    [Google Scholar]
  30. 30.  Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD et al. 2003. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat. Med. 9:1498–505
    [Google Scholar]
  31. 31.  Coyle EF 2005. Improved muscular efficiency displayed as Tour de France champion matures. J. Appl. Physiol. 98:2191–96
    [Google Scholar]
  32. 32.  Coyle EF, Costill DL, Lesmes GR 1979. Leg extension power and muscle fiber composition. Med. Sci. Sports 11:12–15
    [Google Scholar]
  33. 33.  Dejam A, Hunter CJ, Pelletier MM, Hsu PL, Machado RF et al. 2005. Erythrocytes are the major intravascular storage sites of nitrite in human blood. Blood 106:734–39
    [Google Scholar]
  34. 34.  De Smet S, Van Thienen R, Deldicque L, James R, Sale C et al. 2016. Nitrate intake promotes shift in muscle fiber type composition during sprint interval training in hypoxia. Front. Physiol. 7:233
    [Google Scholar]
  35. 35.  Dietrich A, Audiffren M 2011. The reticular-activating hypofrontality (RAH) model of acute exercise. Neurosci. Biobehav. Rev. 35:61305–25
    [Google Scholar]
  36. 36.  Doel JJ, Benjamin N, Hector MP, Rogers M, Allaker RP 2005. Evaluation of bacterial nitrate reduction in the human oral cavity. Eur. J. Oral. Sci. 113:114–19
    [Google Scholar]
  37. 37.  Dufour SP, Patel RP, Brandon A, Teng X, Pearson J et al. 2010. Erythrocyte-dependent regulation of human skeletal muscle blood flow: role of varied oxyhemoglobin and exercise on nitrite, S-nitrosohemoglobin, and ATP. Am. J. Physiol. Heart Circ. Physiol. 299:6H1936–46
    [Google Scholar]
  38. 38.  Duncan C, Dougall H, Johnston P, Green S, Brogan R et al. 1995. Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate. Nat. Med. 1:546–51
    [Google Scholar]
  39. 39.  Eggebeen J, Kim-Shapiro DB, Haykowsky M, Morgan TM, Basu S 2016. One week of daily dosing with beetroot juice improves submaximal endurance and blood pressure in older patients with heart failure and preserved ejection fraction. JACC Heart Fail 4:6428–37
    [Google Scholar]
  40. 40.  Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A et al. 2011. Exercise training increases size of hippocampus and improves memory. PNAS 108:73017–22
    [Google Scholar]
  41. 41.  Evans RW, Fernstrom JD, Thompson J, Morris SM, Kuller LH 2004. Biochemical responses of healthy subjects during dietary supplementation with L-arginine. J. Nutr. Biochem. 15:534–39
    [Google Scholar]
  42. 42.  Ferguson SK, Hirai DM, Copp SW, Holdsworth CT, Allen JD et al. 2013. Impact of dietary nitrate supplementation via beetroot juice on exercising muscle vascular control in rats. J. Physiol. 591:2547–57
    [Google Scholar]
  43. 43.  Ferguson SK, Holdsworth CT, Wright JL, Fees AJ, Allen JD et al. 2015. Microvascular oxygen pressures in muscles comprised of different fiber types: impact of dietary nitrate supplementation. Nitric Oxide 48:38–43
    [Google Scholar]
  44. 44.  Féry Y-A, Ferry A, Hofe AV, Rieu M 1997. Effect of physical exhaustion on cognitive functioning. Percept. Motor Skills 84:1291–98
    [Google Scholar]
  45. 45.  Fulford J, Winyard PG, Vanhatalo A, Bailey SJ, Blackwell JR, Jones AM 2013. Influence of dietary nitrate supplementation on human skeletal muscle metabolism and force production during maximum voluntary contractions. Pflugers Arch 465:4517–28
    [Google Scholar]
  46. 46.  Gasier HG, Reinhold AR, Loiselle AR, Soutiere SE, Fothergill DM 2017. Effects of oral sodium nitrate on forearm blood flow, oxygenation and exercise performance during acute exposure to hypobaric hypoxia (4300 m). Nitric Oxide 69:1–9
    [Google Scholar]
  47. 47.  Gibala MJ, Hawley JA 2017. Sprinting toward fitness. Cell Metab 25:5988–90
    [Google Scholar]
  48. 48.  Gilchrist M, Winyard PG, Fulford J, Anning C, Shore AC, Benjamin N 2014. Dietary nitrate supplementation improves reaction time in type 2 diabetes: development and application of a novel nitrate-depleted beetroot juice placebo. Nitric Oxide 40:67–74
    [Google Scholar]
  49. 49.  Govoni M, Jansson , Weitzberg E, Lundberg JO 2008. The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash. Nitric Oxide 19:333–37
    [Google Scholar]
  50. 50.  Green DJ, Maiorana A, O'Driscoll G, Taylor R 2004. Effect of exercise training on endothelium-derived nitric oxide function in humans. J. Physiol. 561:1–25
    [Google Scholar]
  51. 51.  Haider G, Folland JP 2014. Nitrate supplementation enhances the contractile properties of human skeletal muscle. Med. Sci. Sports Exerc. 46:122234–43
    [Google Scholar]
  52. 52.  Haskell C, Thompson K, Jones AM, Blackwell J, Winyard P et al. 2011. Nitrate-rich beetroot juice modulates cerebral blood flow and cognitive performance in humans. Appetite 57:2560
    [Google Scholar]
  53. 53.  Hernández A, Schiffer TA, Ivarsson N, Cheng AJ, Bruton JD et al. 2012. Dietary nitrate increases tetanic [Ca2+]i and contractile force in mouse fast-twitch muscle. J. Physiol. 590:153575–83
    [Google Scholar]
  54. 54.  Hirai DM, Zelt JT, Jones JH, Castanhas LG, Bentley RF et al. 2017. Dietary nitrate supplementation and exercise tolerance in patients with heart failure with reduced ejection fraction. Am. J. Physiol. Regul. Integr. Comp. Physiol. 312:1R13–22
    [Google Scholar]
  55. 55.  Hoon MW, Hopkins WG, Jones AM, Martin DT, Halson SL et al. 2014.a Nitrate supplementation and high-intensity performance in competitive cyclists. Appl. Physiol. Nutr. Metab. 39:1043–49
    [Google Scholar]
  56. 56.  Hoon MW, Jones AM, Johnson NA, Blackwell JR, Broad EM et al. 2014.b The effect of variable doses of inorganic nitrate-rich beetroot juice on simulated 2,000-m rowing performance in trained athletes. Int. J. Sports Physiol. Perform. 9:615–20
    [Google Scholar]
  57. 57.  Hopkins WG, Hawley JA, Burke LM 1999. Design and analysis of research on sport performance enhancement. Med. Sci. Sports Exerc. 31:472–85
    [Google Scholar]
  58. 58.  Hord NG, Tang Y, Bryan NS 2009. Food sources of nitrates and nitrites: the physiologic context for potential health benefits. Am. J. Clin. Nutr. 90:1–10
    [Google Scholar]
  59. 59.  Horiuchi M, Endo J, Dobashi S, Handa Y, Kiuchi M, Koyama K 2017. Muscle oxygenation profiles between active and inactive muscles with nitrate supplementation under hypoxic exercise. Physiol. Rep. 5:20e13475
    [Google Scholar]
  60. 60.  Jajja A, Sutyarjoko A, Lara J, Rennie K, Brandt K et al. 2014. Beetroot supplementation lowers daily systolic blood pressure in older, overweight subjects. Nutr. Res. 34:10868–75
    [Google Scholar]
  61. 61.  Jensen L, Bangsbo J, Hellsten Y 2004. Effect of high intensity training on capillarization and presence of angiogenic factors in human skeletal muscle. J. Physiol. 557:571–82
    [Google Scholar]
  62. 62.  Jones AM 2006. The physiology of the world record holder for the women's marathon. Int. J. Sports Sci. Coaching 11:101–16
    [Google Scholar]
  63. 63.  Jones AM 2014. Influence of dietary nitrate on the physiological determinants of exercise performance: a critical review. Appl. Physiol. Nutr. Metab. 39:91019–28
    [Google Scholar]
  64. 64.  Jones AM, Ferguson SK, Bailey SJ, Vanhatalo A, Poole DC 2016. Fiber type-specific effects of dietary nitrate. Exerc. Sport Sci. Rev. 44:253–60
    [Google Scholar]
  65. 65.  Jones AM, Poole DC 2005. Introduction to oxygen uptake kinetics and historical development of the discipline. Oxygen Uptake Kinetics in Sport, Exercise and Medicine AM Jones, DC Poole 3–35 London: Routledge
    [Google Scholar]
  66. 66.  Jonvik KL, Nyakayiru J, van Loon LJC, Verdijk LB 2015. Can elite athletes benefit from dietary nitrate supplementation?. J. Appl. Physiol. 119:759–61
    [Google Scholar]
  67. 67.  Jungersten L, Ambring A, Wall B, Wennmalm A 1997. Both physical fitness and acute exercise regulate nitric oxide formation in healthy humans. J. Appl. Physiol. 82:760–64
    [Google Scholar]
  68. 68.  Kelly J, Fulford J, Vanhatalo A, Blackwell JR, French O et al. 2013. Effects of short-term dietary nitrate supplementation on blood pressure, O2 uptake kinetics, and muscle and cognitive function in older adults. Am. J. Physiol. Regul. Integr. Comp. Physiol. 304:2R73–83
    [Google Scholar]
  69. 69.  Kelly J, Vanhatalo A, Bailey SJ, Wylie LJ, Tucker C et al. 2014. Dietary nitrate supplementation: effects on plasma nitrite and pulmonary O2 uptake dynamics during exercise in hypoxia and normoxia. Am. J. Physiol. Regul. Integr. Comp. Physiol. 307:7R920–30
    [Google Scholar]
  70. 70.  Kemp GJ, Meyerspeer M, Moser E 2007. Absolute quantification of phosphorus metabolite concentrations in human muscle in vivo by 31P MRS: a quantitative review. NMR Biomed 20:555–65
    [Google Scholar]
  71. 71.  Kenjale AA, Ham KL, Stabler T, Robbins JL, Johnson JL, Vanbruggen M 2011. Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. J. Appl. Physiol. 110:1582–91
    [Google Scholar]
  72. 72.  Kinnunen S, Mänttäri S 2012. Specific effects of endurance and sprint training on protein expression of calsequestrin and SERCA in mouse skeletal muscle. J. Muscle Res. Cell Motil. 33:123–30
    [Google Scholar]
  73. 73.  Kleinbongard P, Dejam A, Lauer T, Jax T, Kerber S, Gharini P et al. 2006. Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans. Free Radic. Biol. Med. 40:295–302
    [Google Scholar]
  74. 74.  Kozlov AV, Dietrich B, Nohl H 2003. Various intracellular compartments cooperate in the release of nitric oxide from glycerol trinitrate in liver. Br. J. Pharmacol. 139:989–97
    [Google Scholar]
  75. 75.  Kozlov AV, Staniek K, Nohl H 1999. Nitrite reductase activity is a novel function of mammalian mitochondria. FEBS Lett 454:127–30
    [Google Scholar]
  76. 76.  Kuznetsov AV, Tiivel T, Sikk P, Kaambre T, Kay L et al. 1996. Striking differences between the kinetics of regulation of respiration by ADP in slow-twitch and fast-twitch muscles in vivo. Eur. J. Biochem. 241:909–15
    [Google Scholar]
  77. 77.  Lane SC, Hawley JA, Desbrow B, Jones AM, Blackwell JR et al. 2014. Single and combined effects of beetroot juice and caffeine supplementation on cycling time trial performance. Appl. Physiol. Nutr. Metab. 39:1050–57
    [Google Scholar]
  78. 78.  Lansley KE, Winyard PG, Bailey SJ, Vanhatalo A, Wilkerson DP et al. 2011.a Acute dietary nitrate supplementation improves cycling time trial performance. Med. Sci. Sports Exerc. 43:61125–31
    [Google Scholar]
  79. 79.  Lansley KE, Winyard PG, Fulford J, Vanhatalo A, Bailey SJ et al. 2011.b Dietary nitrate supplementation reduces the O2 cost of walking and running: a placebo-controlled study. J. Appl. Physiol. 110:3591–600
    [Google Scholar]
  80. 80.  Lanza IR, Wigmore DM, Befroy DE, Kent-Braun JA 2006. In vivo ATP production during free-flow and ischaemic muscle contractions in humans. J. Physiol. 577:353–67
    [Google Scholar]
  81. 81.  Larsen FJ, Schiffer TA, Borniquel S, Sahlin K, Ekblom B 2011. Dietary inorganic nitrate improves mitochondrial efficiency in humans. Cell Metab 13:2149–59
    [Google Scholar]
  82. 82.  Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B 2010. Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise. Free Radic. Biol. Med. 48:342–47
    [Google Scholar]
  83. 83.  Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B 2007. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol 191:159–66
    [Google Scholar]
  84. 84.  Lauer T, Heiss C, Balzer J, Kehmeier E, Mangold S et al. 2008. Age-dependent endothelial dysfunction is associated with failure to increase plasma nitrite in response to exercise. Basic Res. Cardiol. 103:291–97
    [Google Scholar]
  85. 85.  Lefferts WK, Hughes WE, White CN, Brutsaert TD, Heffernan KS 2016. Effect of acute nitrate supplementation on neurovascular coupling and cognitive performance in hypoxia. Appl. Physiol. Nutr. Metab. 41:2133–41
    [Google Scholar]
  86. 86.  Li H, Cui H, Kundu TK, Alzawahra W, Zweier JL 2008. Nitric oxide production from nitrite occurs primarily in tissues not in the blood: critical role of xanthine oxidase and aldehyde oxidase. J. Biol. Chem. 283:17855–63
    [Google Scholar]
  87. 87.  Lira VA, Benton CR, Yan Z, Bonen A 2010. PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity. Am. J. Physiol. Endocrinol. Metab. 299:2145–61
    [Google Scholar]
  88. 88.  Lundberg JO, Carlström M, Larsen FJ, Weitzberg E 2010. Roles of dietary inorganic nitrate in cardiovascular health and disease. Cardiovasc. Res. 89:525–32
    [Google Scholar]
  89. 89.  Lundberg JO, Weitzberg E 2009. NO generation from inorganic nitrate and nitrite: role in physiology, nutrition and therapeutics. Arch. Pharmacol. Res. 32:1119–26
    [Google Scholar]
  90. 90.  Lundberg JO, Weitzberg E, Lundberg JM, Alving K 1994. Intragastric nitric oxide production in humans: measurements in expelled air. Gut 35:1543–46
    [Google Scholar]
  91. 91.  MacLeod KE, Nugent SF, Barr SI, Koehle MS, Sporer BC et al. 2015. Acute beetroot juice supplementation does not improve cycling performance in normoxia or moderate hypoxia. Int. J. Sport Nutr. Exerc. Metab. 25:4359–66
    [Google Scholar]
  92. 92.  Mahler M 1985. First-order kinetics of muscle oxygen consumption, and equivalent proportionality between QO2 and phosphorylcreatine level. Implications for the control of respiration. J. Gen. Physiol. 86:135–65
    [Google Scholar]
  93. 93.  Maréchal G, Gailly P 1999. Effects of nitric oxide on the contraction of skeletal muscle. Cell Mol. Life Sci. 55:8–91088–102
    [Google Scholar]
  94. 94.  Martin K, Smee D, Thompson K, Rattray B 2014. Dietary nitrate does not improve repeated sprint performance. Int. J. Sports Physiol. Perform. 9:5845–50
    [Google Scholar]
  95. 95.  Masschelein E, Van Thienen R, Wang X, Van Schepdael A, Thomis M, Hespel P 2012. Dietary nitrate improves muscle but not cerebral oxygenation status during exercise in hypoxia. J. Appl. Physiol. 113:5736–45
    [Google Scholar]
  96. 96.  Maughan RJ, Greenhaff PL, Hespel P 2011. Dietary supplements for athletes: emerging trends and recurring themes. J. Sports Sci. 29:Suppl. 1S57–66
    [Google Scholar]
  97. 97.  McConell GK, Bradley SJ, Stephens TJ, Canny BJ, Kingwell BA et al. 2007. Skeletal muscle nNOS protein content is increased by exercise training in humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293:821–28
    [Google Scholar]
  98. 98.  McMahon NF, Leveritt MD, Pavey TG 2017. The effect of dietary nitrate supplementation on endurance exercise performance in healthy adults: a systematic review and meta-analysis. Sports Med 47:4735–56
    [Google Scholar]
  99. 99.  McMorris T, Graydon J 1996. The effect of exercise on the decision-making performance of experienced and inexperienced soccer players. Res. Q. Exerc. Sport 67:1109–14
    [Google Scholar]
  100. 100.  Merry TL, Lynch GS, McConell GK 2010. Downstream mechanisms of nitric oxide-mediated skeletal muscle glucose uptake during contraction. Am. J. Physiol. Regul. Integr. Comp. Physiol. 299:R1656–65
    [Google Scholar]
  101. 101.  Mo L, Wang Y, Geary L, Corey C, Alef MJ et al. 2012. Nitrite activates AMP kinase to stimulate mitochondrial biogenesis independent of soluble guanylate cyclase. Free Radic. Biol. Med. 53:1440–50
    [Google Scholar]
  102. 102.  Modin A, Björne H, Herulf M, Alving K, Weitzberg E et al. 2001. Nitrite-derived nitric oxide: a possible mediator of acidic–metabolic vasodilation. Acta Physiol. Scand. 171:9–16
    [Google Scholar]
  103. 103.  Moncada S, Higgs A 1993. The L-arginine-nitric oxide pathway. N. Engl. J. Med. 329:2002–12
    [Google Scholar]
  104. 104.  Moncada S, Palmer RMJ, Higgs EA 1989. Biosynthesis of nitric oxide from L-arginine. Biochem. Pharmacol. 38:1709–15
    [Google Scholar]
  105. 105.  Muggeridge DJ, Howe CC, Spendiff O, Pedlar C, James PE et al. 2013. The effects of a single dose of concentrated beetroot juice on performance in trained flatwater kayakers. Int. J. Sport Nutr. Exerc. Metab. 23:5498–506
    [Google Scholar]
  106. 106.  Muggeridge DJ, Howe CC, Spendiff O, Pedlar C, James PE, Easton C 2014.a A single dose of beetroot juice enhances cycling performance in simulated altitude. Med. Sci. Sports Exerc. 46:1143–50
    [Google Scholar]
  107. 107.  Muggeridge DJ, Sculthorpe N, Grace FM, Willis G, Thornhill L et al. 2014.b Acute whole body UVA irradiation combined with nitrate ingestion enhances time trial performance in trained cyclists. Nitric Oxide 48:3–9
    [Google Scholar]
  108. 108.  Muggeridge DJ, Sculthorpe N, James PE, Easton C 2017. The effects of dietary nitrate supplementation on the adaptations to sprint interval training in previously untrained males. J. Sci. Med. Sport 20:192–97
    [Google Scholar]
  109. 109.  Nyakayiru JM, Jonvik JL, Pinckaers PJ, Senden J, van Loon LJ, Verdijk LB 2017.a No effect of acute and 6-day nitrate supplementation on VO2 and time-trial performance in highly trained cyclists. Int. J. Sport Nutr. Exerc. Metab. 27:11–17
    [Google Scholar]
  110. 110.  Nyakayiru JM, Jonvik KL, Trommelen J, Pinckaers PJ, Senden JM et al. 2017.b Beetroot juice supplementation improves high-intensity intermittent type exercise performance in trained soccer players. Nutrients 9:3314
    [Google Scholar]
  111. 111.  Nybäck L, Glännerud C, Larsson G, Weitzberg E, Shannon OM, McGawley K 2017. Physiological and performance effects of nitrate supplementation during roller-skiing in normoxia and normobaric hypoxia. Nitric Oxide 70:1–8
    [Google Scholar]
  112. 112.  Omar SA, Artime E, Webb AJ 2012. A comparison of organic and inorganic nitrates/nitrites. Nitric Oxide 26:229–40
    [Google Scholar]
  113. 113.  Omar SA, Webb AJ, Lundberg JO, Weitzberg E 2016. Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases. J. Intern. Med. 279:4315–36
    [Google Scholar]
  114. 114.  Pawlak-Chaouch M, Boissière J, Gamelin FX, Cuvelier G, Berthoin S, Aucouturier J 2016. Effect of dietary nitrate supplementation on metabolic rate during rest and exercise in human: a systematic review and a meta-analysis. Nitric Oxide 29;53:65–76
    [Google Scholar]
  115. 115.  Peacock O, Tjønna AE, James P, Wisløff U, Welde B et al. 2012. Dietary nitrate does not enhance running performance in elite cross-country skiers. Med. Sci. Sports Exerc. 44:2213–19
    [Google Scholar]
  116. 116.  Peeling P, Cox GR, Bullock N, Burke LM 2015. Beetroot juice improves on-water 500 M time-trial performance, and laboratory-based paddling economy in national and international-level kayak athletes. Int. J. Sport Nutr. Exerc. Metab. 25:278–84
    [Google Scholar]
  117. 117.  Percival JM, Anderson KN, Huang P, Adams ME, Froehner SC 2010. Golgi and sarcolemmal neuronal NOS differentially regulate contraction-induced fatigue and vasoconstriction in exercising mouse skeletal muscle. J. Clin. Investig. 120:816–26
    [Google Scholar]
  118. 118.  Petrie M, Rejeski WJ, Basu S, Laurienti PJ, Marsh AP et al. 2017. Beet root juice: an ergogenic aid for exercise and the aging brain. J. Gerontol. A Biol. Sci. Med. Sci. 72:91284–89
    [Google Scholar]
  119. 119.  Piknova B, Kocharyan A, Schechter AN, Silva AC 2011. The role of nitrite in neurovascular coupling. Brain Res 1407:62–68
    [Google Scholar]
  120. 120.  Polgar J, Johnson MA, Weightman D, Appleton D 1973. Data on fibre size in thirty-six human muscles. An autopsy study. J. Neurol. Sci. 19:307–18
    [Google Scholar]
  121. 121.  Porcelli S, Ramaglia M, Bellistri G, Pavei G, Pugliese L et al. 2015. Aerobic fitness affects the exercise performance responses to nitrate supplementation. Med. Sci. Sports Exerc. 47:1643–51
    [Google Scholar]
  122. 122.  Presley TD, Morgan AR, Bechtold E, Clodfelter W, Dove RW et al. 2011. Acute effect of a high nitrate diet on brain perfusion in older adults. Nitric Oxide 24:134–42
    [Google Scholar]
  123. 123.  Puype J, Ramaekers M, Van Thienen R, Deldicque L, Hespel P 2015. No effect of dietary nitrate supplementation on endurance training in hypoxia. Scand. J. Med. Sci. Sports 25:2234–41
    [Google Scholar]
  124. 124.  Qin L, Liu X, Sun Q, Fan Z, Xia D et al. 2012. Sialin (SLC17A5) functions as a nitrate transporter in the plasma membrane. PNAS 109:13434–39
    [Google Scholar]
  125. 125.  Rammos C, Hendgen-Cotta UB, Sobierajski J, Bernard A, Kelm M, Rassaf T 2014. Dietary nitrate reverses vascular dysfunction in older adults with moderately increased cardiovascular risk. J. Am. Coll. Cardiol. 63:151584–85
    [Google Scholar]
  126. 126.  Reilly T, Smith D 1986. Effect of work intensity on performance in a psychomotor task during exercise. Ergonomics 29:4601–6
    [Google Scholar]
  127. 127.  Richardson RS, Noyszewski EA, Kendrick KF, Leigh JS, Wagner PD 1995. Myoglobin O2 desaturation during exercise. Evidence of limited O2 transport. J. Clin. Investig. 96:1916
    [Google Scholar]
  128. 128.  Rimer EG, Peterson LR, Coggan AR, Martin JC 2016. Increase in maximal cycling power with acute dietary nitrate supplementation. Int. J. Sports Physiol. Perform. 11:6715–20
    [Google Scholar]
  129. 129.  Roberts LD, Ashmore T, McNally BD, Murfitt SA, Fernandez BO et al. 2017. Inorganic nitrate mimics exercise-stimulated muscular fiber-type switching and myokine and γ-aminobutyric acid release. Diabetes 66:3674–88
    [Google Scholar]
  130. 130.  Rossetti GMK, Macdonald JH, Wylie LJ, Little SJ, Newton V et al. 2017. Dietary nitrate supplementation increases acute mountain sickness severity and sense of effort during hypoxic exercise. J. Appl. Physiol. 123:4983–92
    [Google Scholar]
  131. 131.  Sandbakk SB, Sandbakk Ø, Peacock O, James P, Welde B et al. 2015. Effects of acute supplementation of L-arginine and nitrate on endurance and sprint performance in elite athletes. Nitric Oxide 48:10–15
    [Google Scholar]
  132. 132.  Schena F, Cuzzolin L, Rossi L, Pasetto M, Benoni G 2002. Plasma nitrite/nitrate and erythropoietin levels in cross-country skiers during altitude training. J. Sports Med. Phys. Fitness 42:129–34
    [Google Scholar]
  133. 133.  Secher NH, Seifert T, Van Lieshout JJ 2008. Cerebral blood flow and metabolism during exercise: implications for fatigue. J. Appl. Physiol. 104:1306–14
    [Google Scholar]
  134. 134.  Shannon OM, Duckworth L, Barlow MJ, Deighton K, Matu J et al. 2017. Effects of dietary nitrate supplementation on physiological responses, cognitive function, and exercise performance at moderate and very-high simulated altitude. Front. Physiol. 8:401
    [Google Scholar]
  135. 135.  Shannon OM, Duckworth L, Barlow MJ, Woods D, Lara J et al. 2016. Dietary nitrate supplementation enhances high-intensity running performance in moderate normobaric hypoxia, independent of aerobic fitness. Nitric Oxide 59:63–70
    [Google Scholar]
  136. 136.  Shepherd AI, Gilchrist M, Winyard PG, Jones AM, Hallmann E et al. 2015. Effects of dietary nitrate supplementation on the oxygen cost of exercise and walking performance in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled crossover trial. Free Radic. Biol. Med. 86:200–8
    [Google Scholar]
  137. 137.  Shepherd AI, Wilkerson DP, Dobson L, Kelly J, Winyard PG et al. 2015. The effect of dietary nitrate supplementation on the oxygen cost of cycling, walking performance and resting blood pressure in individuals with chronic obstructive pulmonary disease: a double blind placebo controlled, randomised control trial. Nitric Oxide 48:31–37
    [Google Scholar]
  138. 138.  Shiva S, Huang Z, Grubina R, Sun J, Ringwood LA et al. 2007. Deoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respiration. Circ. Res. 100:654–61
    [Google Scholar]
  139. 139.  Siervo M, Lara J, Jajja A, Sutyarjoko A, Ashor AW et al. 2015. Ageing modifies the effects of beetroot juice supplementation on 24-hour blood pressure variability: an individual participant meta-analysis. Nitric Oxide 47:97–105
    [Google Scholar]
  140. 140.  Siervo M, Lara J, Ogbonmwan I, Mathers JC 2013. Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis. J. Nutr. 143:6818–26
    [Google Scholar]
  141. 141.  Siervo M, Oggioni C, Jakovljevic DG, Trenell M, Mathers JC et al. 2016. Dietary nitrate does not affect physical activity or outcomes in healthy older adults in a randomized, cross-over trial. Nutr. Res. 36:121361–69
    [Google Scholar]
  142. 142.  Sindler AL, Fleenor BS, Calvert JW, Marshall KD, Zigler ML et al. 2011. Nitrite supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness with aging. Aging Cell 10:3429–37
    [Google Scholar]
  143. 143.  Stamler JS, Meissner G 2001. Physiology of nitric oxide in skeletal muscle. Physiol. Rev. 81:1209–37
    [Google Scholar]
  144. 144.  Tesch PA, Karlsson J 1985. Muscle fiber types and size in trained and untrained muscles of elite athletes. J. Appl. Physiol. 59:1716–20
    [Google Scholar]
  145. 145.  Thomas DD, Liu X, Kantrow SP, Lancaster JR Jr. 2001. The biological lifetime of nitric oxide: implications for the perivascular dynamics of NO and O2. PNAS 98:355–60
    [Google Scholar]
  146. 146.  Thompson C, Vanhatalo A, Jell H, Fulford J, Carter J et al. 2016. Dietary nitrate supplementation improves sprint and high-intensity intermittent running performance. Nitric Oxide 61:55–61
    [Google Scholar]
  147. 147.  Thompson C, Wylie LJ, Blackwell JR, Fulford J, Black MI et al. 2017. Influence of dietary nitrate supplementation on physiological and muscle metabolic adaptations to sprint interval training. J. Appl. Physiol. 122:3642–52
    [Google Scholar]
  148. 148.  Thompson C, Wylie LJ, Fulford J, Kelly J, Black MI et al. 2015. Dietary nitrate improves sprint performance and cognitive function during prolonged intermittent exercise. Eur. J. Appl. Physiol. 115:91825–34
    [Google Scholar]
  149. 149.  Thompson KG, Turner L, Prichard J, Dodd F, Kennedy DO et al. 2014. Influence of dietary nitrate supplementation on physiological and cognitive responses to incremental cycle exercise. Respir. Physiol. Neurobiol. 193:11–20
    [Google Scholar]
  150. 150.  Vanhatalo A, Bailey SJ, Blackwell JR, Dimenna FJ, Pavey TG et al. 2010. Acute and chronic effects of dietary nitrate supplementation on blood pressure and the physiological responses to moderate-intensity and incremental exercise. Am. J. Physiol. Regul. Integr. Comp. Physiol. 299:41121–31
    [Google Scholar]
  151. 151.  Vanhatalo A, Bailey SJ, DiMenna FJ, Blackwell JR, Wallis GA, Jones AM 2013. No effect of acute L-arginine supplementation on O2 cost or exercise tolerance. Eur. J. Appl. Physiol. 113:71805–19
    [Google Scholar]
  152. 152.  Vanhatalo A, Fulford J, Bailey SJ, Blackwell JR, Winyard PG, Jones AM 2011. Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia. J. Physiol. 589:5517–28
    [Google Scholar]
  153. 153.  Vanhatalo A, Jones AM, Blackwell JR, Winyard PG, Fulford J 2014. Dietary nitrate accelerates postexercise muscle metabolic recovery and O2 delivery in hypoxia. J. Appl. Physiol. 1985 117:1460–70
    [Google Scholar]
  154. 154.  Vanin AF, Bevers LM, Slama-Schwok A, van Faassen EE 2007. Nitric oxide synthase reduces nitrite to NO under anoxia. Cell. Mol. Life Sci. 64:96–103
    [Google Scholar]
  155. 155.  Viner RI, Williams TD, Schöneich C 2000. Nitric oxide-dependent modification of the sarcoplasmic reticulum Ca-ATPase: localization of cysteine target sites. Free Radic. Biol. Med. 29:489–96
    [Google Scholar]
  156. 156.  Vukosavljevic N, Jaron D, Barbee KA, Buerk DG 2006. Quantifying the L-arginine paradox in vivo. Microvasc. Res. 71:48–54
    [Google Scholar]
  157. 157.  Wagner DA, Schultz DS, Deen WM, Young VR, Tannenbaum SR 1983. Metabolic fate of an oral dose of 15N-labeled nitrate in humans: effect of diet supplementation with ascorbic acid. Cancer Res 43:1921–25
    [Google Scholar]
  158. 158.  Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z et al. 2008. Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension 51:784–90
    [Google Scholar]
  159. 159.  Weitzberg E, Lundberg JO 1998. Nonenzymatic nitric oxide production in humans. Nitric Oxide 2:1–7
    [Google Scholar]
  160. 160.  Whitfield J, Gamu D, Heigenhauser GJF, Van Loon LJC, Spriet LL et al. 2017. Beetroot juice increases human muscle force without changing Ca2+-handling proteins. Med. Sci. Sports Exerc. 49:102016–24
    [Google Scholar]
  161. 161.  Whitfield J, Ludzki A, Heigenhauser GJ, Senden JM, Verdijk LB et al. 2016. Beetroot juice supplementation reduces whole body oxygen consumption but does not improve indices of mitochondrial efficiency in human skeletal muscle. J. Physiol. 594:2421–35
    [Google Scholar]
  162. 162.  Wightman EL, Haskell-Ramsay CF, Thompson KG, Blackwell JR, Winyard PG et al. 2015. Dietary nitrate modulates cerebral blood flow parameters and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Physiol. Behav. 149:149–58
    [Google Scholar]
  163. 163.  Wilkerson DP, Hayward GM, Bailey SJ, Vanhatalo A, Blackwell JR, Jones AM 2012. Influence of acute dietary nitrate supplementation on 50 mile time trial performance in well-trained cyclists. Eur. J. Appl. Physiol. 112:4127–34
    [Google Scholar]
  164. 164.  Woessner MN, McIlvenna LC, Ortiz de Zevallos J, Neil C, Allen JD 2017. Dietary nitrate supplementation in cardiovascular health: an ergogenic aid or exercise therapeutic?. Am. J. Physiol. Heart Circ. Physiol. 314:H195–212
    [Google Scholar]
  165. 165.  Wu W, Morris SM 1997. Arginine metabolism: nitric oxide and beyond. Biochem. J. 336:1–17
    [Google Scholar]
  166. 166.  Wylie LJ, Bailey SJ, Kelly J, Blackwell JR, Vanhatalo A, Jones AM 2016. Influence of beetroot juice supplementation on intermittent exercise performance. Eur. J. Appl. Physiol. 116:2415–25
    [Google Scholar]
  167. 167.  Wylie LJ, Kelly J, Bailey SJ, Blackwell JR, Skiba PF et al. 2013. Beetroot juice and exercise: pharmacodynamic and dose-response relationships. J. Appl. Physiol. 115:3325–36
    [Google Scholar]
  168. 168.  Wylie LJ, Mohr M, Krustrup P, Jackman SR, Ermidis G et al. 2013. Dietary nitrate supplementation improves team sport-specific intense intermittent exercise performance. Eur. J. Appl. Physiol. 113:71673–84
    [Google Scholar]
  169. 169.  Wylie LJ, Ortiz de Zevallos J, Isidore T, Nyman L, Vanhatalo A et al. 2016. Dose-dependent effects of dietary nitrate on the oxygen cost of moderate-intensity exercise: acute versus chronic supplementation. Nitric Oxide 57:30–39
    [Google Scholar]
  170. 170.  Ysart G, Miller P, Barrett G, Farrington D, Lawrance P, Harrison N 1999. Dietary exposures to nitrate in the UK. Food Addit. Contam. 16:521–32
    [Google Scholar]
  171. 171.  Zamani P, Rawat D, Shiva-Kumar P, Geraci S, Bhuva R et al. 2015. Effect of inorganic nitrate on exercise capacity in heart failure with preserved ejection fraction. Circulation 131:4371–80
    [Google Scholar]
  172. 172.  Zhang Z, Naughton D, Winyard PG, Benjamin N, Blake DR et al. 1998. Generation of nitric oxide by a nitrite reductase activity of xanthine oxidase: a potential pathway for nitric oxide formation in the absence of nitric oxide synthase activity. Biochem. Biophys. Res. Commun. 249:767–72
    [Google Scholar]
/content/journals/10.1146/annurev-nutr-082117-051622
Loading
/content/journals/10.1146/annurev-nutr-082117-051622
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error