• 1
    Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov 2008; 7: 156167.
  • 2
    Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 1988; 333: 664666.
  • 3
    Moncada S, Palmer RM, Higgs EA. The discovery of nitric oxide as the endogenous nitrovasodilator. Hypertension 1988; 12: 365372.
  • 4
    Modin A, Bjorne H, Herulf M, Alving K, Weitzberg E, Lundberg JO. Nitrite-derived nitric oxide: a possible mediator of ‘acidic-metabolic’ vasodilation. Acta Physiol Scand 2001; 171: 916.
  • 5
    Demoncheaux EA, Higenbottam TW, Foster PJ, Borland CD, Smith AP, Marriott HM, Bee D, Akamine S, Davies MB. Circulating nitrite anions are a directly acting vasodilator and are donors for nitric oxide. Clin Sci 2002; 102: 7783.
  • 6
    Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S, Yang BK, Waclawiw MA, Zalos G, Xu X, Huang KT, Shields H, Kim-Shapiro DB, Schechter AN, Cannon RO 3rd, Gladwin MT. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med 2003; 9: 14981505.
  • 7
    Webb A, Bond R, McLean P, Uppal R, Benjamin N, Ahluwalia A. Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage. Proc Natl Acad Sci U S A 2004; 101: 1368313688.
  • 8
    Pannala AS, Mani AR, Spencer JP, Skinner V, Bruckdorfer KR, Moore KP, Rice-Evans CA. The effect of dietary nitrate on salivary, plasma, and urinary nitrate metabolism in humans. Free Radic Biol Med 2003; 34: 576584.
  • 9
    Sobko T, Marcus C, Govoni M, Kamiya S. Dietary nitrate in Japanese traditional foods lowers diastolic blood pressure in healthy volunteers. Nitric Oxide 2010; 22: 136140.
  • 10
    Yamori Y, Miura A, Taira K. Implications from and for food cultures for cardiovascular diseases: Japanese food, particularly Okinawan diets. Asia Pac J Clin Nutr 2001; 10: 144145.
  • 11
    FB H. The Mediterranean diet and mortality – olive oil and beyond. N Engl J Med 2003; 348: 25952596.
  • 12
    Keys A. Mediterranean diet and public health: personal reflections. Am J Clin Nutr 1995; 61: 1321S1323.
  • 13
    Mente A, de Koning L, Shannon HS, Anand SS. A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Arch Intern Med 2009; 169: 659669.
  • 14
    Tsuji KMS, Morita Y, Shibata T, Kaneta N, Wakabayashi K, Uchibori-Hase S, Ide S, Fujiwara K, Suzuki H, Ito Y. Naturally occurring of nitrite and nitrate existing in various raw and processed foods. J Food Hyg Soc Jpn 1993; 34: 294302.
  • 15
    Donaldson AN. The Relation of Protein Foods to Hypertension. Cal West Med 1926; 24: 328331.
  • 16
    Sacks FM, Rosner B, Kass EH. Blood pressure in vegetarians. Am J Epidemiol 1974; 100: 390398.
  • 17
    Armstrong B, van Merwyk AJ, Coates H. Blood pressure in Seventh-day Adventist vegetarians. Am J Epidemiol 1977; 105: 444449.
  • 18
    Armstrong B, Clarke H, Martin C, Ward W, Norman N, Masarei J. Urinary sodium and blood pressure in vegetarians. Am J Clin Nutr 1979; 32: 24722476.
  • 19
    Joshipura KJ, Ascherio A, Manson JE, Stampfer MJ, Rimm EB, Speizer FE, Hennekens CH, Spiegelman D, Willett WC. Fruit and vegetable intake in relation to risk of ischemic stroke. JAMA 1999; 282: 12331239.
  • 20
    Joshipura KJ, Hu FB, Manson JE, Stampfer MJ, Rimm EB, Speizer FE, Colditz G, Ascherio A, Rosner B, Spiegelman D, Willett WC. The effect of fruit and vegetable intake on risk for coronary heart disease. Ann Intern Med 2001; 134: 11061114.
  • 21
    Kapil V, Webb AJ, Ahluwalia A. Inorganic nitrate and the cardiovascular system. Heart 2010; 96: 17031709.
  • 22
    Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, Bray GA, Vogt TM, Cutler JA, Windhauser MM, Lin PH, Karanja N. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med 1997; 336: 11171124.
  • 23
    Rouse IL, Beilin LJ, Armstrong BK, Vandongen R. Blood-pressure-lowering effect of a vegetarian diet: controlled trial in normotensive subjects. Lancet 1983; 1: 510.
  • 24
    Lindahl O, Lindwall L, Spangberg A, Stenram A, Ockerman PA. A vegan regimen with reduced medication in the treatment of hypertension. Br J Nutr 1984; 52: 1120.
  • 25
    Gangolli SD, van den Brandt PA, Feron VJ, Janzowsky C, Koeman JH, Speijers GJ, Spiegelhalder B, Walker R, Wisnok JS. Nitrate, nitrite and N-nitroso compounds. Eur J Pharmacol 1994; 292: 138.
  • 26
    White JW Jr. Relative significance of dietary sources of nitrate and nitrite. J Agric Food Chem 1975; 23: 886891.
  • 27
    van Loon AIM, van Klaveren JD. Nitraatinname van de Nederiandse bevolking. Voeding 1991; 52: 96100.
  • 28
    Knight TM, Forman D, Al-Dabbagh SA, Doll R. Estimation of dietary intake of nitrate and nitrite in Great Britain. Food and Chemical Toxicology : An International Journal Published for the British Industrial Biological Research Association 1987; 25: 277285.
  • 29
    Binkerd EF, Kolari OE. The history and use of nitrate and nitrite in the curing of meat. Food Cosmet Toxicol 1975; 13: 655661.
  • 30
    Machha A, Schechter A. Dietary nitrite and nitrate: a review of potential mechanisms of cardiovascular benefits. Eur J Nutr 2011; 50: 293303.
  • 31
    Rocha BS, Gago B, Pereira C, Barbosa RM, Bartesaghi S, Lundberg JO, Radi R, Laranjinha J. Dietary nitrite in nitric oxide biology: a redox interplay with implications for pathophysiology and therapeutics. Curr Drug Targets 2011; 12: 13511363.
  • 32
    Milkowski A, Garg HK, Coughlin JR, Bryan NS. Nutritional epidemiology in the context of nitric oxide biology: a risk-benefit evaluation for dietary nitrite and nitrate. Nitric Oxide 2010; 22: 110119.
  • 33
    Kevil CG, Kolluru GK, Pattillo CB, Giordano T. Inorganic nitrite therapy: historical perspective and future directions. Free Radic Biol Med 2011; 51: 576593.
  • 34
    Omar SA, Artime E, Webb AJ. A comparison of organic and inorganic nitrates/nitrites. Nitric Oxide 2012; 26: 229240.
  • 35
    Tamme T, Reinik M, Roasto M, Juhkam K, Tenno T, Kiis A. Nitrates and nitrites in vegetables and vegetable-based products and their intakes by the Estonian population. Food Addit Contam 2006; 23: 355361.
  • 36
    Santamaria P. Nitrate in vegetables: toxicity, content, intake and EC regulation. J Sci Food Agric 2006; 86: 1017.
  • 37
    Santamaria P, Elia A, Serio F, Todaro E. A survey of nitrate and oxalate content in fresh vegetables. J Sci Food Agric 1999; 79: 18821888.
  • 38
    Santamaria P, Gonnella M, Elia A, Parente A, Serio F. Ways of reducing rocket salad nitrate content. Acta Hortic 2001; 529536.
  • 39
    Meah MN, Harrison N, Davies A. Nitrate and nitrite in foods and the diet. Food Addit Contam 1994; 11: 519532.
  • 40
    Ysart G, Clifford R, Harrison N. Monitoring for nitrate in UK-grown lettuce and spinach. Food Addit Contam 1999; 16: 301306.
  • 41
    Maynard DN, Barker AV, Minotti PL, Peck NH. Nitrate accumulation in vegetables. Adv Agron 1976; 28: 71118.
  • 42
    Corr WJ, Breimer T. Nitrate and Nitrite in Vegetables. Wageningen: Centre for Agricultural Publishing and Documentation (PUDOC), 1979.
  • 43
    Bhattacharjee R, Singh A, Mukhopadhyay S. Use of nitrogen-fixing bacteria as biofertiliser for non-legumes: prospects and challenges. Appl Microbiol Biotechnol 2008; 80: 199209.
  • 44
    Pate JS. Uptake, assimilation and transport of nitrogen compounds by plants. Soil Biol Biochem 1973; 5: 109119.
  • 45
    Andrews M. The partitioning of nitrate assimilation between root and shoot of higher plants. Plant Cell Environ 1986; 9: 511519.
  • 46
    Wallace W. Distribution of nitrate assimilation between the root and shoot of legumes and a comparison with wheat. Physiol Plant 1986; 66: 630636.
  • 47
    Tamme T, Reinik M, Pussa T, Roasto M, Meremae K, Kiis A. Dynamics of nitrate and nitrite content during storage of home-made and small-scale industrially produced raw vegetable juices and their dietary intake. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2010; 27: 487495.
  • 48
    Katan MB. Nitrate in foods: harmful or healthy? Am J Clin Nutr 2009; 90: 1112.
  • 49
    Taylor S. Relative Exposure to Nitrite, Nitrate, and N-Nitroso Compounds from Endogenous and Exogenous Sources. Food Toxicology: A Perspective on the Relative Risks Marcel Dekker Inc 1989; 6364, ISBN 0-8247-8141-4.
  • 50
    Mitchell HH, Shonle HA, Grindley HS. The origin of the nitrates in the urine. J Biol Chem 1916; 24: 461490.
  • 51
    Green LC, Ruiz de Luzuriaga K, Wagner DA, Rand W, Istfan N, Young VR, Tannenbaum SR. Nitrate biosynthesis in man. Proc Natl Acad Sci U S A 1981; 78: 77647768.
  • 52
    Leaf CD, Wishnok JS, Tannenbaum SR. L-arginine is a precursor for nitrate biosynthesis in humans. Biochem Biophys Res Commun 1989; 163: 10321037.
  • 53
    Rhodes P, Leone AM, Francis PL, Struthers AD, Moncada S, Rhodes PM. The L-arginine: nitric oxide pathway is the major source of plasma nitrite in fasted humans. Biochem Biophys Res Commun 1995; 209: 590596.
  • 54
    Penttila PL. Estimation of Food Additive and Pesticide Intakes by Means of A Stepwise Method [Dissertation]. Turku: University of Turku, 1995.
  • 55
    Dejonckheere W, Streubaut W, Drieghe S, Verstraeten R, Braeckman H. Nitrate in food commodities of vegetable origin and the total diet in Belgium, 1992–1993. Microbiologie – Aliments – Nutrition 1994; 12: 359370.
  • 56
    Petersen A, Stoltze S. Nitrate and nitrite in vegetables on the Danish market: content and intake. Food Addit Contam 1999; 16: 291299.
  • 57
    Belitz HD, Grosch W. Food Chemistry, 992. Berlin: Springer-Verlag, 1999.
  • 58
    Chung SY, Kim JS, Kim M, Hong MK, Lee JO, Kim CM, Song IS. Survey of nitrate and nitrite contents of vegetables grown in Korea. Food Addit Contam 2003; 20: 621628.
  • 59
    Pardo-Marín O, Yusà-Pelechà V, Villalba-Martín P, Perez-Dasí JA. Monitoring programme on nitrates in vegetables and vegetable-based baby foods marketed in the Region of Valencia, Spain: levels and estimated daily intake. Food Additives & Contaminants: Part A 2010; 27: 478486.
  • 60
    Menard C, Heraud F, Volatier JL, Leblanc JC. Assessment of Dietary Exposure of Nitrate and Nitrite in France. Food Additives & Contaminants: Part A 2008; 25: 971988.
  • 61
    Thames Water. Water quality report – 2011 data [online]. Available at (last accessed 20 February 2012).
  • 62
    The Open University, Water for life, Section 8. Water and its impurities [online]. Available at (last accessed 20 February 2012).
  • 63
    Queensland Health Dietitians. Foods that contain potassium (K+), April 2012 [online]. Available at (last accessed 14 February 2012).
  • 64
    Comly HH. Landmark article Sept 8, 1945: cyanosis in infants caused by nitrates in well-water. By Hunter H. Comly. JAMA 1987; 257: 27882792.
  • 65
    Walton G. Survey of literature relating to infant methemoglobinemia due to nitrate-contaminated water. Am J Public Health Nations Health 1951; 41: 986996.
  • 66
    Avery AA. Infantile methemoglobinemia: reexamining the role of drinking water nitrates. Environ Health Perspect 1999; 107: 583586.
  • 67
    Willis T. Pharmaceutice Rationalis: Or An Exercitation of the Medicines in Humane Bodies. London: T. Dring, C. Harper, and J. Leigh, 1697.
  • 68
    Hiatt EP. Comparison of the diuretic effects of nitrate salts with other diuretic agents. Am J Physiol 1957; 189: 173176.
  • 69
    Butler AR, Feelisch M. Therapeutic uses of inorganic nitrite and nitrate: from the past to the future. Circulation 2008; 117: 21512159.
  • 70
    Reichert ET, Mitchell SW. On the physiological action of potassium nitrite. Am J Med Sci 1880; 156: 158180.
  • 71
    Stebbing J. Post-prandial syncope due to nitrates in food. Postgrad Med J 1997; 73: 606.
  • 72
    Furchgott RF, Bhadrakom S. Reactions of strips of rabbit aorta to epinephrine, isopropylarterenol, sodium nitrite and other drugs. J Pharmacol Exp Ther 1953; 108: 129143.
  • 73
    Gladwin MT, Shelhamer JH, Schechter AN, Pease-Fye ME, Waclawiw MA, Panza JA, Ognibene FP, Cannon RO 3rd. Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans. Proc Natl Acad Sci U S A 2000; 97: 1148211487.
  • 74
    Tsuchiya K, Takiguchi Y, Okamoto M, Izawa Y, Kanematsu Y, Yoshizumi M, Tamaki T. Malfunction of vascular control in lifestyle-related diseases: formation of systemic hemoglobin-nitric oxide complex (HbNO) from dietary nitrite. J Pharmacol Sci 2004; 96: 395400.
  • 75
    Maher AR, Milsom AB, Gunaruwan P, Abozguia K, Ahmed I, Weaver RA, Thomas P, Ashrafian H, Born GV, James PE, Frenneaux MP. Hypoxic modulation of exogenous nitrite-induced vasodilation in humans. Circulation 2008; 117: 670677.
  • 76
    Curtis E, Hsu LL, Noguchi AC, Geary L, Shiva S. Oxygen regulates tissue nitrite metabolism. Antioxid Redox Signal 2012; 17: 951961.
  • 77
    Lundberg JO, Govoni M. Inorganic nitrate is a possible source for systemic generation of nitric oxide. Free Radic Biol Med 2004; 37: 395400.
  • 78
    Larsen FJ, Ekblom B, Sahlin K, Lundberg JO, Weitzberg E. Effects of dietary nitrate on blood pressure in healthy volunteers. N Engl J Med 2006; 355: 27922793.
  • 79
    Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S, Rashid R, Miall P, Deanfield J, Benjamin N, MacAllister R, Hobbs AJ, Ahluwalia A. Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension 2008; 51: 784790.
  • 80
    Govoni M, Jansson EA, Weitzberg E, Lundberg JO. The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash. Nitric Oxide 2008; 19: 333337.
  • 81
    Petersson J, Carlstrom M, Schreiber O, Phillipson M, Christoffersson G, Jagare A, Roos S, Jansson EA, Persson AE, Lundberg JO, Holm L. Gastroprotective and blood pressure lowering effects of dietary nitrate are abolished by an antiseptic mouthwash. Free Radic Biol Med 2009; 46: 10681075.
  • 82
    Kapil V, Milsom AB, Okorie M, Maleki-Toyserkani S, Akram F, Rehman F, Arghandawi S, Pearl V, Benjamin N, Loukogeorgakis S, Macallister R, Hobbs AJ, Webb AJ, Ahluwalia A. Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO. Hypertension 2010; 56: 274281.
  • 83
    Berry SE, Mulla UZ, Chowienczyk PJ, Sanders TA. Increased potassium intake from fruit and vegetables or supplements does not lower blood pressure or improve vascular function in UK men and women with early hypertension: a randomised controlled trial. Br J Nutr 2010; 104: 18391847.
  • 84
    He FJ, Markandu ND, Coltart R, Barron J, MacGregor GA. Effect of short-term supplementation of potassium chloride and potassium citrate on blood pressure in hypertensives. Hypertension 2005; 45: 571574.
  • 85
    Hobbs AJ. Soluble guanylate cyclase: the forgotten sibling. Trends Pharmacol Sci 1997; 18: 484491.
  • 86
    Dejam A, Hunter CJ, Tremonti C, Pluta RM, Hon YY, Grimes G, Partovi K, Pelletier MM, Oldfield EH, Cannon RO 3rd, Schechter AN, Gladwin MT. Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formation. Circulation 2007; 116: 18211831.
  • 87
    Parker JD, Gori T. Tolerance to the organic nitrates: new ideas, new mechanisms, continued mystery. Circulation 2001; 104: 22632265.
  • 88
    Vanhatalo A, Bailey SJ, Blackwell JR, DiMenna FJ, Pavey TG, Wilkerson DP, Benjamin N, Winyard PG, Jones AM. 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 2010; 299: R11211131.
  • 89
    Bondonno CP, Yang X, Croft KD, Considine MJ, Ward NC, Rich L, Puddey IB, Swinny E, Mubarak A, Hodgson JM. Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: a randomized controlled trial. Free Radic Biol Med 2012; 52: 95102.
  • 90
    Hobbs DA, Kaffa N, George TW, Methven L, Lovegrove JA. Blood pressure-lowering effects of beetroot juice and novel beetroot-enriched bread products in normotensive male subjects. Br J Nutr 2012; 14: 19. [Epub ahead of print].
  • 91
    Mustard JF, Moore S, Packham MA, Kinlough-Rathbone RL. Platelets, thrombosis and atherosclerosis. Prog Biochem Pharmacol 1977; 13: 312325.
  • 92
    Fitzgerald DJ, Roy L, Catella F, FitzGerald GA. Platelet activation in unstable coronary disease. N Engl J Med 1986; 315: 983989.
  • 93
    Radomski MW, Palmer RM, Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet 1987; 2: 10571058.
  • 94
    Radomski MW, Palmer RM, Moncada S. An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci U S A 1990; 87: 51935197.
  • 95
    Benjamin N, O'Driscoll F, Dougall H, Duncan C, Smith L, Golden M, McKenzie H. Stomach NO synthesis. Nature 1994; 368: 502.
  • 96
    Lundberg JO, Weitzberg E, Lundberg JM, Alving K. Intragastric nitric oxide production in humans: measurements in expelled air. Gut 1994; 35: 15431546.
  • 97
    Richardson G, Hicks SL, O'Byrne S, Frost MT, Moore K, Benjamin N, McKnight GM. The ingestion of inorganic nitrate increases gastric S-nitrosothiol levels and inhibits platelet function in humans. Nitric Oxide 2002; 7: 2429.
  • 98
    Rocks SA, Davies CA, Hicks SL, Webb AJ, Klocke R, Timmins GS, Johnston A, Jawad AS, Blake DR, Benjamin N, Winyard PG. Measurement of S-nitrosothiols in extracellular fluids from healthy human volunteers and rheumatoid arthritis patients, using electron paramagnetic resonance spectrometry. Free Radic Biol Med 2005; 39: 937948.
  • 99
    Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993; 329: 20022012.
  • 100
    Lauer T, Preik M, Rassaf T, Strauer BE, Deussen A, Feelisch M, Kelm M. Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action. Proc Natl Acad Sci U S A 2001; 98: 1281412819.
  • 101
    Zweier JL, Wang P, Samouilov A, Kuppusamy P. Enzyme-independent formation of nitric oxide in biological tissues. Nat Med 1995; 1: 804809.
  • 102
    Godber BL, Doel JJ, Sapkota GP, Blake DR, Stevens CR, Eisenthal R, Harrison R. Reduction of nitrite to nitric oxide catalyzed by xanthine oxidoreductase. J Biol Chem 2000; 275: 77577763.
  • 103
    Li H, Samouilov A, Liu X, Zweier JL. Characterization of the magnitude and kinetics of xanthine oxidase-catalyzed nitrite reduction. Evaluation of its role in nitric oxide generation in anoxic tissues. J Biol Chem 2001; 276: 2448224489.
  • 104
    Millar TM, Stevens CR, Benjamin N, Eisenthal R, Harrison R, Blake DR. Xanthine oxidoreductase catalyses the reduction of nitrates and nitrite to nitric oxide under hypoxic conditions. FEBS Lett 1998; 427: 225228.
  • 105
    Zhang Z, Naughton D, Winyard PG, Benjamin N, Blake DR, Symons MC. 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 1998; 249: 767772.
  • 106
    Cortas NK, Wakid NW. Pharmacokinetic aspects of inorganic nitrate ingestion in man. Pharmacol Toxicol 1991; 68: 192195.
  • 107
    Kortboyer JM, Colbers EPH, Vaessen HAMG, Groen K, Zeilmaker MJ, Slob W, Speijers GJA, Meulenbelt J. A Pilot-Study to Investigate Nitrate and Nitrite Kinetics in Healthy Volunteers with Normal and Artificially Increased Gastric Ph after Sodium Nitrate Ingestion Proceeds of the International Workshop on Health Aspects of Nitrate and Its Metabolites (Partcularly Nitrite), November 8–10, 1994. Bilthoven: Council of Europe Press, 1995; 269284.
  • 108
    Bryan NS, Fernandez BO, Bauer SM, Garcia-Saura MF, Milsom AB, Rassaf T, Maloney RE, Bharti A, Rodriguez J, Feelisch M. Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nat Chem Biol 2005; 1: 290297.
  • 109
    McKnight GM, Duncan CW, Leifert C, Golden MH. Dietary nitrate in man: friend or foe? Br J Nutr 1999; 81: 349358.
  • 110
    Wagner DA, Schultz DS, Deen WM, Young VR, Tannenbaum SR. Metabolic fate of an oral dose of N-15-labeled nitrate in humans – effect of diet supplementation with ascorbic-acid. Cancer Res 1983; 43: 19211925.
  • 111
    van Velzen AG, Sips AJ, Schothorst RC, Lambers AC, Meulenbelt J. The oral bioavailability of nitrate from nitrate-rich vegetables in humans. Toxicol Lett 2008; 181: 177181.
  • 112
    Hunault CC, van Velzen AG, Sips AJ, Schothorst RC, Meulenbelt J. Bioavailability of sodium nitrite from an aqueous solution in healthy adults. Toxicol Lett 2009; 190: 4853.
  • 113
    Bartholomew B, Hill MJ. The pharmacology of dietary nitrate and the origin of urinary nitrate. Food Chem Toxicol 1984; 22: 789795.
  • 114
    Florin TH, Neale G, Cummings JH. The effect of dietary nitrate on nitrate and nitrite excretion in man. Br J Nutr 1990; 64: 387397.
  • 115
    Tannenbaum SR, Weisman M, Fett D. The effect of nitrate intake on nitrite formation in human saliva. Food Cosmet Toxicol 1976; 14: 549552.
  • 116
    Spiegelhalder B, Eisenbrand G, Preussmann R. Influence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compounds. Food Cosmet Toxicol 1976; 14: 545548.
  • 117
    Duncan C, Dougall H, Johnston P, Green S, Brogan R, Leifert C, Smith L, Golden M, Benjamin N. Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate. Nat Med 1995; 1: 546551.
  • 118
    Doel JJ, Benjamin N, Hector MP, Rogers M, Allaker RP. Evaluation of bacterial nitrate reduction in the human oral cavity. Eur J Oral Sci 2005; 113: 1419.
  • 119
    Gladwin MT, Schechter AN, Kim-Shapiro DB, Patel RP, Hogg N, Shiva S, Cannon RO 3rd, Kelm M, Wink DA, Espey MG, Oldfield EH, Pluta RM, Freeman BA, Lancaster JR Jr, Feelisch M, Lundberg JO. The emerging biology of the nitrite anion. Nat Chem Biol 2005; 1: 308314.
  • 120
    Huang Z, Shiva S, Kim-Shapiro DB, Patel RP, Ringwood LA, Irby CE, Huang KT, Ho C, Hogg N, Schechter AN, Gladwin MT. Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control. J Clin Invest 2005; 115: 20992107.
  • 121
    Gladwin MT, Kim-Shapiro DB. The functional nitrite reductase activity of the heme-globins. Blood 2008; 112: 26362647.
  • 122
    Shiva S, Huang Z, Grubina R, Sun J, Ringwood LA, MacArthur PH, Xu X, Murphy E, Darley-Usmar VM, Gladwin MT. Deoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respiration. Circ Res 2007; 100: 654661.
  • 123
    Tiso M, Tejero J, Basu S, Azarov I, Wang X, Simplaceanu V, Frizzell S, Jayaraman T, Geary L, Shapiro C, Ho C, Shiva S, Kim-Shapiro DB, Gladwin MT. Human neuroglobin functions as a redox-regulated nitrite reductase. J Biol Chem 2011; 286: 1827718289.
  • 124
    Petersen MG, Dewilde S, Fago A. Reactions of ferrous neuroglobin and cytoglobin with nitrite under anaerobic conditions. J Inorg Biochem 2008; 102: 17771782.
  • 125
    Webb AJ, Milsom AB, Rathod KS, Chu WL, Qureshi S, Lovell MJ, Lecomte FM, Perrett D, Raimondo C, Khoshbin E, Ahmed Z, Uppal R, Benjamin N, Hobbs AJ, Ahluwalia A. Mechanisms underlying erythrocyte and endothelial nitrite reduction to nitric oxide in hypoxia: role for xanthine oxidoreductase and endothelial nitric oxide synthase. Circ Res 2008; 103: 957964.
  • 126
    Li H, Cui H, Kundu TK, Alzawahra W, Zweier JL. Nitric oxide production from nitrite occurs primarily in tissues not in the blood: critical role of xanthine oxidase and aldehyde oxidase. J Biol Chem 2008; 283: 1785517863.
  • 127
    Badejo AM, Hodnette C, Dhaliwal JS, Casey DB, Pankey E, Murthy SN, Nossaman BD, Hyman AL, Kadowitz PJ. Mitochondrial aldehyde dehydrogenase mediates vasodilator responses of glyceryl trinitrate and sodium nitrite in the pulmonary vascular bed of the rat. Am J of Physiol – Heart and Circulatory Physiology 2010; 299: H819826.
  • 128
    Gautier C, van Faassen E, Mikula I, Martasek P, Slama-Schwok A. Endothelial nitric oxide synthase reduces nitrite anions to NO under anoxia. Biochem Biophys Res Commun 2006; 341: 816821.
  • 129
    Vanin AF, Bevers LM, Slama-Schwok A, van Faassen EE. Nitric oxide synthase reduces nitrite to NO under anoxia. Cell Mol Life Sci 2007; 64: 96103.
  • 130
    Milsom AB, Patel NS, Mazzon E, Tripatara P, Storey A, Mota-Filipe H, Sepodes B, Webb AJ, Cuzzocrea S, Hobbs AJ, Thiemermann C, Ahluwalia A. Role for endothelial nitric oxide synthase in nitrite-induced protection against renal ischemia-reperfusion injury in mice. Nitric Oxide 2010; 22: 141148.
  • 131
    Li H, Liu X, Cui H, Chen YR, Cardounel AJ, Zweier JL. Characterization of the mechanism of cytochrome P450 reductase-cytochrome P450-mediated nitric oxide and nitrosothiol generation from organic nitrates. J Biol Chem 2006; 281: 1254612554.
  • 132
    Raikhman LM, Annaev BB. [Nature of the free-radical states in microsomes]. Biofizika 1971; 16: 11351137.
  • 133
    Duthu GS, Shertzer HG. Effect of nitrite on rabbit liver mixed-function oxidase activity. Drug Metab Dispos 1979; 7: 263269.
  • 134
    Reutov VP, Sorokina EG. NO-synthase and nitrite-reductase components of nitric oxide cycle. Biochemistry (Mosc) 1998; 63: 874884.
  • 135
    Nohl H, Staniek K, Sobhian B, Bahrami S, Redl H, Kozlov AV. Mitochondria recycle nitrite back to the bioregulator nitric monoxide. Acta Biochim Pol 2000; 47: 913921.
  • 136
    Kozlov AV, Staniek K, Nohl H. Nitrite reductase activity is a novel function of mammalian mitochondria. FEBS Lett 1999; 454: 127130.
  • 137
    Aamand R, Dalsgaard T, Jensen FB, Simonsen U, Roepstorff A, Fago A. Generation of nitric oxide from nitrite by carbonic anhydrase: a possible link between metabolic activity and vasodilation. Am J Physiol Heart Circ Physiol 2009; 297: H20682074.
  • 138
    Dalsgaard T, Simonsen U, Fago A. Nitrite-dependent vasodilation is facilitated by hypoxia and is independent of known NO-generating nitrite reductase activities. Am J Physiol Heart Circ Physiol 2007; 292: H30723078.
  • 139
    Rudolph TK, Rudolph V, Edreira MM, Cole MP, Bonacci G, Schopfer FJ, Woodcock SR, Franek A, Pekarova M, Khoo NK, Hasty AH, Baldus S, Freeman BA. Nitro-fatty acids reduce atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2010; 30: 938945.
  • 140
    Chobanyan-Jürgens K, Schwarz A, Böhmer A, Beckmann B, Gutzki F-M, Michaelsen JT, Stichtenoth DO, Tsikas D. Renal carbonic anhydrases are involved in the reabsorption of endogenous nitrite. Nitric Oxide 2012; 26: 126131.
  • 141
    McKnight GM, Smith LM, Drummond RS, Duncan CW, Golden M, Benjamin N. Chemical synthesis of nitric oxide in the stomach from dietary nitrate in humans. Gut 1997; 40: 211214.
  • 142
    Lundberg JO, Weitzberg E. NO generation from nitrite and its role in vascular control. Arterioscler Thromb Vasc Biol 2005; 25: 915922.
  • 143
    Widlansky ME, Gokce N, Keaney JF Jr, Vita JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol 2003; 42: 11491160.
  • 144
    Kleinbongard P, Dejam A, Lauer T, Rassaf T, Schindler A, Picker O, Scheeren T, Godecke A, Schrader J, Schulz R, Heusch G, Schaub GA, Bryan NS, Feelisch M, Kelm M. Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals. Free Radic Biol Med 2003; 35: 790796.
  • 145
    Kleinbongard P, Dejam A, Lauer T, Jax T, Kerber S, Gharini P, Balzer J, Zotz RB, Scharf RE, Willers R, Schechter AN, Feelisch M, Kelm M. Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans. Free Radic Biol Med 2006; 40: 295302.
  • 146
    Rassaf T, Heiss C, Hendgen-Cotta U, Balzer J, Matern S, Kleinbongard P, Lee A, Lauer T, Kelm M. Plasma nitrite reserve and endothelial function in the human forearm circulation. Free Radic Biol Med 2006; 41: 295301.
  • 147
    Stokes KY, Dugas TR, Tang Y, Garg H, Guidry E, Bryan NS. Dietary nitrite prevents hypercholesterolemic microvascular inflammation and reverses endothelial dysfunction. Am J Physiol Heart Circ Physiol 2009; 296: H12811288.
  • 148
    Bahra M, Kapil V, Pearl V, Ghosh S, Ahluwalia A. Inorganic nitrate ingestion improves vascular compliance but does not alter flow-mediated dilatation in healthy volunteers. Nitric Oxide 2012; 26: 197202.
  • 149
    Cheriyan J, Webb AJ, Sarov-Blat L, Elkhawad M, Wallace SM, Maki-Petaja KM, Collier DJ, Morgan J, Fang Z, Willette RN, Lepore JJ, Cockcroft JR, Sprecher DL, Wilkinson IB. Inhibition of p38 mitogen-activated protein kinase improves nitric oxide-mediated vasodilatation and reduces inflammation in hypercholesterolemia. Circulation 2011; 123: 515523.
  • 150
    Sindler AL, Fleenor BS, Calvert JW, Marshall KD, Zigler ML, Lefer DJ, Seals DR. Nitrite supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness with aging. Aging Cell 2011; 10: 429437.
  • 151
    Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a ‘set up’ for vascular disease. Circulation 2003; 107: 139146.
  • 152
    Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part II: the aging heart in health: links to heart disease. Circulation 2003; 107: 346354.
  • 153
    Lakatta EG. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part III: cellular and molecular clues to heart and arterial aging. Circulation 2003; 107: 490497.
  • 154
    Cecelja M, Chowienczyk P. Dissociation of aortic pulse wave velocity with risk factors for cardiovascular disease other than hypertension: a systematic review. Hypertension 2009; 54: 13281336.
  • 155
    Wilkinson IB, Franklin SS, Cockcroft JR. Nitric oxide and the regulation of large artery stiffness: from physiology to pharmacology. Hypertension 2004; 44: 112116.
  • 156
    McEniery CM, Wilkinson IB. Large artery stiffness and inflammation. J Hum Hypertens 2005; 19: 507509.
  • 157
    Lalaoui MZ, El Midaoui A, de Champlain J, Moreau P. Is there a role for reactive oxygen species in arterial medial elastocalcinosis? Vascul Pharmacol 2007; 46: 201206.
  • 158
    Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol 2010; 55: 13181327.
  • 159
    Ahanchi SS, Tsihlis ND, Kibbe MR. The role of nitric oxide in the pathophysiology of intimal hyperplasia. J Vasc Surg 2007; 45: A64A73.
  • 160
    Alef MJ, Vallabhaneni R, Carchman E, Morris SM, Shiva S, Wang Y, Kelley EE, Tarpey MM, Gladwin MT, Tzeng E, Zuckerbraun BS. Nitrite-generated NO circumvents dysregulated arginine/NOS signaling to protect against intimal hyperplasia in Sprague-Dawley rats. J Clin Invest 2011; 121: 16461656.
  • 161
    Duranski MR, Greer JJ, Dejam A, Jaganmohan S, Hogg N, Langston W, Patel RP, Yet SF, Wang X, Kevil CG, Gladwin MT, Lefer DJ. Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver. J Clin Invest 2005; 115: 12321240.
  • 162
    Lu P, Liu F, Yao Z, Wang CY, Chen DD, Tian Y, Zhang JH, Wu YH. Nitrite-derived nitric oxide by xanthine oxidoreductase protects the liver against ischemia-reperfusion injury. Hepatobiliary Pancreat Dis Int 2005; 4: 350355.
  • 163
    Jung KH, Chu K, Ko SY, Lee ST, Sinn DI, Park DK, Kim JM, Song EC, Kim M, Roh JK. Early intravenous infusion of sodium nitrite protects brain against in vivo ischemia-reperfusion injury. Stroke 2006; 37: 27442750.
  • 164
    Bryan NS, Calvert JW, Elrod JW, Gundewar S, Ji SY, Lefer DJ. Dietary nitrite supplementation protects against myocardial ischemia-reperfusion injury. Proc Natl Acad Sci U S A 2007; 104: 1914419149.
  • 165
    Tripatara P, Patel NS, Webb A, Rathod K, Lecomte FM, Mazzon E, Cuzzocrea S, Yaqoob MM, Ahluwalia A, Thiemermann C. Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion injury in vivo: role for xanthine oxidoreductase. J Am Soc Nephrol 2007; 18: 570580.
  • 166
    Dezfulian C, Raat N, Shiva S, Gladwin MT. Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics. Cardiovasc Res 2007; 75: 327338.
  • 167
    Webb A, Ahluwalia A. Mechanisms of nitrite reduction in ischemia in the cardiovascular system: therapeutic potential. In: Nitric Oxide (2nd Edition) Biology and Pathobiology, ed. Ignarro L . London: Academic Press, 2010; 555586.
  • 168
    Presley TD, Morgan AR, Bechtold E, Clodfelter W, Dove RW, Jennings JM, Kraft RA, Bruce King S, Laurienti PJ, Jack Rejeski W, Burdette JH, Kim-Shapiro DB, Miller GD. Acute effect of a high nitrate diet on brain perfusion in older adults. Nitric Oxide 2011; 24: 3442.
  • 169
    Lauer T, Heiss C, Balzer J, Kehmeier E, Mangold S, Leyendecker T, Rottler J, Meyer C, Merx M, Kelm M, Rassaf T. Age-dependent endothelial dysfunction is associated with failure to increase plasma nitrite in response to exercise. Basic Res Cardiol 2008; 103: 291297.
  • 170
    Kenjale AA, Ham KL, Stabler T, Robbins JL, Johnson JL, Vanbruggen M, Privette G, Yim E, Kraus WE, Allen JD. Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. J Appl Physiol 2011; 110: 15821591.
  • 171
    Barstow TJ, Lamarra N, Whipp BJ. Modulation of muscle and pulmonary O2 uptakes by circulatory dynamics during exercise. J Appl Physiol 1990; 68: 979989.
  • 172
    Grassi B, Poole DC, Richardson RS, Knight DR, Erickson BK, Wagner PD. Muscle O2 uptake kinetics in humans: implications for metabolic control. J Appl Physiol 1996; 80: 988998.
  • 173
    Jones AM, Wilkerson DP, Koppo K, Wilmshurst S, Campbell IT. Inhibition of nitric oxide synthase by L-NAME speeds phase II pulmonary.VO2 kinetics in the transition to moderate-intensity exercise in man. J Physiol 2003; 552: 265272.
  • 174
    Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol 2007; 191: 5966.
  • 175
    Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise. Free Radic Biol Med 2010; 48: 342347.
  • 176
    Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, Dimenna FJ, Wilkerson DP, Tarr J, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol 2009; 107: 11441155.
  • 177
    Bailey SJ, Fulford J, Vanhatalo A, Winyard PG, Blackwell JR, DiMenna FJ, Wilkerson DP, Benjamin N, Jones AM. Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans. J Appl Physiol 2010; 109: 135148.
  • 178
    Lansley KE, Winyard PG, Fulford J, Vanhatalo A, Bailey SJ, Blackwell JR, DiMenna FJ, Gilchrist M, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of walking and running: a placebo-controlled study. J Appl Physiol 2011; 110: 591600.
  • 179
    Lansley KE, Winyard PG, Bailey SJ, Vanhatalo A, Wilkerson DP, Blackwell JR, Gilchrist M, Benjamin N, Jones AM. Acute dietary nitrate supplementation improves cycling time trial performance. Med Sci Sports Exerc 2011; 43: 11251131.
  • 180
    Vanhatalo A, Fulford J, Bailey SJ, Blackwell JR, Winyard PG, Jones AM. Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia. J Physiol 2011; 589: 55175528.
  • 181
    Cermak NM, Gibala MJ, van Loon LJ. Nitrate supplementation's improvement of 10-km time-trial performance in trained cyclists. Int J Sport Nutr Exerc Metab 2012; 22: 6471.
  • 182
    Larsen FJ, Schiffer TA, Borniquel S, Sahlin K, Ekblom B, Lundberg JO, Weitzberg E. Dietary inorganic nitrate improves mitochondrial efficiency in humans. Cell Metab 2011; 13: 149159.
  • 183
    Zhu S-G, Kukreja RC, Das A, Chen Q, Lesnefsky EJ, Xi L. Dietary Nitrate Supplementation Protects Against Doxorubicin-Induced Cardiomyopathy by Improving Mitochondrial Function. J Am Coll Cardiol 2011; 57: 21812189.
  • 184
    Gladwin MT, Hunter CJ, Dejam A, Blood AB, Shields H, Kim-Shapiro D, Machado RF, Tarekegn S, Mulla N, Hopper AO, Schechter AN, Power GG. Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator. Nat Med 2004; 10: 11221127.
  • 185
    Ingram TE, Pinder AG, Bailey DM, Fraser AG, James PE. Low-dose sodium nitrite vasodilates hypoxic human pulmonary vasculature by a means that is not dependent on a simultaneous elevation in plasma nitrite. Am J Physiol Heart Circ Physiol 2010; 298: H331339.
  • 186
    Dias-Junior CA, Gladwin MT, Tanus-Santos JE. Low-dose intravenous nitrite improves hemodynamics in a canine model of acute pulmonary thromboembolism. Free Radic Biol Med 2006; 41: 17641770.
  • 187
    Baliga RS, Milsom AB, Ghosh SM, Trinder SL, Macallister RJ, Ahluwalia A, Hobbs AJ. Dietary nitrate ameliorates pulmonary hypertension: cytoprotective role for endothelial nitric oxide synthase and xanthine oxidoreductase. Circulation 2012; 125: 29222932.
  • 188
    Gago B, Lundberg JO, Barbosa RM, Laranjinha J. Red wine-dependent reduction of nitrite to nitric oxide in the stomach. Free Radic Biol Med 2007; 43: 12331242.
  • 189
    Rocha BS, Gago B, Barbosa RM, Laranjinha J. Dietary polyphenols generate nitric oxide from nitrite in the stomach and induce smooth muscle relaxation. Toxicology 2009; 265: 4148.
  • 190
    Zand J, Lanza F, Garg HK, Bryan NS. All-natural nitrite and nitrate containing dietary supplement promotes nitric oxide production and reduces triglycerides in humans. Nutr Res 2011; 31: 262269.
  • 191
    Gago B, Nyström T, Cavaleiro C, Rocha BS, Barbosa RM, Laranjinha J, Lundberg JO. The potent vasodilator ethyl nitrite is formed upon reaction of nitrite and ethanol under gastric conditions. Free Radic Biol Med 2008; 45: 404412.
  • 192
    Moya MP, Gow AJ, Califf RM, Goldberg RN, Stamler JS. Inhaled ethyl nitrite gas for persistent pulmonary hypertension of the newborn. Lancet 2002; 360: 141143.
  • 193
    O'Donnell VB, Eiserich JP, Chumley PH, Jablonsky MJ, Krishna NR, Kirk M, Barnes S, Darley-Usmar VM, Freeman BA. Nitration of unsaturated fatty acids by nitric oxide-derived reactive nitrogen species peroxynitrite, nitrous acid, nitrogen dioxide, and nitronium ion. Chem Res Toxicol 1998; 12: 8392.
  • 194
    Cui T, Schopfer FJ, Zhang J, Chen K, Ichikawa T, Baker PR, Batthyany C, Chacko BK, Feng X, Patel RP, Agarwal A, Freeman BA, Chen YE. Nitrated fatty acids: endogenous anti-inflammatory signaling mediators. J Biol Chem 2006; 281: 3568635698.
  • 195
    Li Y, Zhang J, Schopfer FJ, Martynowski D, Garcia-Barrio MT, Kovach A, Suino-Powell K, Baker PRS, Freeman BA, Chen YE, Xu HE. Molecular recognition of nitrated fatty acids by PPAR[gamma]. Nat Struct Mol Biol 2008; 15: 865867.
  • 196
    Borniquel S, Jansson EÅ, Cole MP, Freeman BA, Lundberg JO. Nitrated oleic acid up-regulates PPARγ and attenuates experimental inflammatory bowel disease. Free Radic Biol Med 2010; 48: 499505.
  • 197
    Kelley EE, Batthyany CI, Hundley NJ, Woodcock SR, Bonacci G, Del Rio JM, Schopfer FJ, Lancaster JR Jr, Freeman BA, Tarpey MM. Nitro-oleic acid, a novel and irreversible inhibitor of xanthine oxidoreductase. J Biol Chem 2008; 283: 3617636184.
  • 198
    Liu H, Jia Z, Soodvilai S, Guan G, Wang MH, Dong Z, Symons JD, Yang T. Nitro-oleic acid protects the mouse kidney from ischemia and reperfusion injury. Am J Physiol Renal Physiol 2008; 295: F942949.
  • 199
    Nitrites, nitrosamines, and cancer. Lancet 1968; 1: 10711072.
  • 200
    Magee PN, Barnes JM. The production of malignant primary hepatic tumours in the rat by feeding dimethylnitrosamine. Br J Cancer 1956; 10: 114122.
  • 201
    Sakshaug J, Sognen E, Hansen MA, Koppang N. Dimethylnitrosamine; its hepatotoxic effect in sheep and its occurrence in toxic batches of herring meal. Nature 1965; 206: 12611262.
  • 202
    Sander J. [Can nitrites in the human diet be the cause of cancerogenesis through formation of nitrosamines?]. Arch Hyg Bakteriol 1967; 151: 2228.
  • 203
    Druckrey H, Schildbach A, Schmaehl D, Preussmann R, Ivankovic S. [Quantitative Analysis of the Carcinogenic Effect of Diethylnitrosamine]. Arzneimittelforschung 1963; 13: 841851.
  • 204
    Bartsch H, Ohshima H, Pignatelli B. Inhibitors of endogenous nitrosation. Mechanisms and implications in human cancer prevention. Mutat Res 1988; 202: 307324.
  • 205
    World Health Organisation. Fifty-ninth Report of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Geneva: Evaluation of Certain Food Additives, 2002.
  • 206
    Mensinga TT, Speijers GJ, Meulenbelt J. Health implications of exposure to environmental nitrogenous compounds. Toxicol Rev 2003; 22: 4151.
  • 207
    Alexander J, Benford D, Cockburn A, Cravedi JP, Dogliotti E, Domenico AD, Fernández-Cruz ML, Fink-Gremmels J, Fürst P, Galli C, Grandjean P, Gzyl J, Heinemeyer G, Johansson N, Mutti A, Schlatter J, van Leeuwen R, van Peteghem C, Verger P. Opinion of the Scientific Panel on Contaminants in the Food chain on a request from the European Commission to perform a scientific risk assessment on nitrate in vegetables. The European Food Safety Authority Journal 2008; 689: 179.
  • 208
    Winter JW, Paterson S, Scobie G, Wirz A, Preston T, McColl KE. N-nitrosamine generation from ingested nitrate via nitric oxide in subjects with and without gastroesophageal reflux. Gastroenterology 2007; 133: 164174.
  • 209
    World Cancer Research Fund / American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington DC: AICR, 2007.
  • 210
    Steinmetz KA, Potter JD. Vegetables, fruit, and cancer prevention: a review. J Am Diet Assoc 1996; 96: 10271039.
  • 211
    Mirvish SS, Wallcave L, Eagen M, Shubik P. Ascorbate-nitrite reaction: possible means of blocking the formation of carcinogenic N-nitroso compounds. Science 1972; 177: 6568.
  • 212
    Combet E, Paterson S, Iijima K, Winter J, Mullen W, Crozier A, Preston T, McColl KEL. Fat transforms ascorbic acid from inhibiting to promoting acid-catalysed N-nitrosation. Gut 2007; 56: 16781684.
  • 213
    Kuroiwa Y, Yamada M, Matsui K, Okamura T, Ishii Y, Masumura K, Tasaki M, Umemura T, Mitsumori K, Nohmi T, Hirose M, Nishikawa A. Combined ascorbic acid and sodium nitrite treatment induces oxidative DNA damage-associated mutagenicity in vitro, but lacks initiation activity in rat forestomach epithelium. Toxicol Sci 2008; 104: 274282.
  • 214
    Hirose M, Tanaka H, Takahashi S, Futakuchi M, Fukushima S, Ito N. Effects of sodium nitrite and catechol, 3-methoxycatechol, or butylated hydroxyanisole in combination in a rat multiorgan carcinogenesis model. Cancer Res 1993; 53: 3237.
  • 215
    Kawabe M, Takaba K, Yoshida Y, Hirose M. Effects of combined treatment with phenolic compounds and sodium nitrite on two-stage carcinogenesis and cell proliferation in the rat stomach. Jpn J Cancer Res 1994; 85: 1725.
  • 216
    Yoshida Y, Hirose M, Takaba K, Kimura J, Ito N. Induction and promotion of forestomach tumors by sodium nitrite in combination with ascorbic acid or sodium ascorbate in rats with or without N-methyl-N'-nitro-N-nitrosoguanidine pre-treatment. Int J Cancer 1994; 56: 124128.
  • 217
    Miyauchi M, Nakamura H, Furukawa F, Son HY, Nishikawa A, Hirose M. Promoting effects of combined antioxidant and sodium nitrite treatment on forestomach carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine. Cancer Lett 2002; 178: 1924.
  • 218
    Combet E, El Mesmari A, Preston T, Crozier A, McColl KE. Dietary phenolic acids and ascorbic acid: influence on acid-catalyzed nitrosative chemistry in the presence and absence of lipids. Free Radic Biol Med 2010; 48: 763771.
  • 219
    Kuroiwa Y, Ishii Y, Umemura T, Kanki K, Mitsumori K, Nishikawa A, Nakazawa H, Hirose M. Combined treatment with green tea catechins and sodium nitrite selectively promotes rat forestomach carcinogenesis after initiation with N-methyl-N'- nitro-N-nitrosoguanidine. Cancer Sci 2007; 98: 949957.
  • 220
    Aschebrook-Kilfoy B, Ward MH, Gierach GL, Schatzkin A, Hollenbeck AR, Sinha R, Cross AJ. Epithelial ovarian cancer and exposure to dietary nitrate and nitrite in the NIH-AARP Diet and Health Study. Eur J Cancer Prev 2012; 21: 6572. 10.1097/CEJ.0b013e328347622f.
  • 221
    Ward MH, Kilfoy BA, Weyer PJ, Anderson KE, Folsom AR, Cerhan JR. Nitrate intake and the risk of thyroid cancer and thyroid disease. Epidemiology 2010; 21: 389395.
  • 222
    Aschebrook-Kilfoy B, Cross AJ, Stolzenberg-Solomon RZ, Schatzkin A, Hollenbeck AR, Sinha R, Ward MH. Pancreatic cancer and exposure to dietary nitrate and nitrite in the NIH-AARP Diet and Health Study. Am J Epidemiol 2011; 174: 305315.
  • 223
    Ward MH, Heineman EF, Markin RS, Weisenburger DD. Adenocarcinoma of the stomach and esophagus and drinking water and dietary sources of nitrate and nitrite. Int J Occup Environ Health 2008; 14: 193197.
  • 224
    Ward MH, Cerhan JR, Colt JS, Hartge P. Risk of non-Hodgkin lymphoma and nitrate and nitrite from drinking water and diet. Epidemiology 2006; 17: 375382.
  • 225
    Ward M, Rusiecki J, Lynch C, Cantor K. Nitrate in public water supplies and the risk of renal cell carcinoma. Cancer Causes Control 2007; 18: 11411151.
  • 226
    Kapadia GJ, Azuine MA, Rao GS, Arai T, Iida A, Tokuda H. Cytotoxic effect of the red beetroot (Beta vulgaris L.) extract compared to doxorubicin (Adriamycin) in the human prostate (PC-3) and breast (MCF-7) cancer cell lines. Anticancer Agents Med Chem 2011; 11: 280284.
  • 227
    Kapadia GJ, Tokuda H, Konoshima T, Nishino H. Chemoprevention of lung and skin cancer by Beta vulgaris (beet) root extract. Cancer Lett 1996; 100: 211214.
  • 228
    Kapadia GJ, Azuine MA, Sridhar R, Okuda Y, Tsuruta A, Ichiishi E, Mukainake T, Takasaki M, Konoshima T, Nishino H, Tokuda H. Chemoprevention of DMBA-induced UV-B promoted, NOR-1-induced TPA promoted skin carcinogenesis, and DEN-induced phenobarbital promoted liver tumors in mice by extract of beetroot. Pharmacol Res 2003; 47: 141148.
  • 229
    Lechner JF, Wang LS, Rocha CM, Larue B, Henry C, McIntyre CM, Riedl KM, Schwartz SJ, Stoner GD. Drinking water with red beetroot food color antagonizes esophageal carcinogenesis in N-nitrosomethylbenzylamine-treated rats. J Med Food 2010; 13: 733739.
  • 230
    Georgiev V, Weber J, Kneschke E-M, Denev P, Bley T, Pavlov A. Antioxidant activity and phenolic content of betalain extracts from intact plants and hairy root cultures of the red beetroot Beta vulgaris cv. Detroit dark red. Plant Foods Hum Nutr 2010; 65: 105111.
  • 231
    Morant R, Jungi WF, Koehli C, Senn HJ. [Why do cancer patients use alternative medicine?]. Schweiz Med Wochenschr 1991; 121: 10291034.
  • 232
    Obrist R, von Meiss M, Obrecht JP. [The use of paramedical treatment methods by cancer patients. A inquiry on 101 ambulatory patients]. Dtsch Med Wochenschr 1986; 111: 283287.