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Dietary nitrate in man: friend or foe?

  • G. M. McKnight (a1), C. W. Duncan (a1) (a2), C. Leifert (a3) and M. H. Golden (a1) (a2)

Based on the premise that dietary nitrate is detrimental to human health, increasingly stringent regulations are being instituted to lower nitrate levels in food and water. Not only does this pose a financial challenge to water boards and a threat to vegetable production in Northern Europe, but also may be eliminating an important non-immune mechanism for host defence. Until recently nitrate was perceived as a purely harmful dietary component which causes infantile methaemoglobinaemia, carcinogenesis and possibly even teratogenesis. Epidemiological studies have failed to substantiate this. It has been shown that dietary nitrate undergoes enterosalivary circulation. It is recirculated in the blood, concentrated by the salivary glands, secreted in the saliva and reduced to nitrite by facultative Gram-positive anaerobes (Staphylococcus sciuri and S. intermedius) on the tongue. Salivary nitrite is swallowed into the acidic stomach where it is reduced to large quantities of NO and other oxides of N and, conceivably, also contributes to the formation of systemic S-nitrosothiols. NO and solutions of acidified nitrite, mimicking gastric conditions, have been shown to have antimicrobial activity against a wide range of organisms. In particular, acidified nitrite is bactericidal for a variety of gastrointestinal pathogens such as Yersinia and Salmonella. NO is known to have vasodilator properties and to modulate platelet function, as are S-nitrosothiols. Thus, nitrate in the diet, which determines reactive nitrogen oxide species production in the stomach (McKnight et al. 1997), is emerging as an effective host defence against gastrointestinal pathogens, as a modulator of platelet activity and possibly even of gastrointestinal motility and microcirculation. Therefore dietary nitrate may have an important therapeutic role to play, not least in the immunocompromised and in refugees who are at particular risk of contracting gastroenteritides.

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Corresponding author
Corresponding author: Professor Michael Golden, fax +(0)1224 699884, email*
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TM Addiscott (1996) Fertilizers and nitrate leaching. In Agricultural Chemicals and the Environment, Issues in Environmental Science and Technology, no. 5, pp. 126 [ RE Hester and RM Harrison , editors]. Cambridge: Royal Society of Chemistry.

E Angaard (1994) Nitric oxide: mediator, murderer and medicine. Lancet 343, 11991206.

TE Arbuckle , GJ Sherman , PN Corey , D Walters & B Lo (1988) Water nitrates and CNS birth defects; a population-based case–control study. Archives of Environmental Health 43, 162167.

R Armijo & AH Coulson (1975) Epidemiology of stomach cancer in Chile: the role of nitrogen fertilizers. International Journal of Epidemiology 4, 301309.

R Armijo , A Gonzales , M Orellana , AH Coulson , JW Sayre & R Detels (1981) Epidemiology of gastric cancer in Chile II. Nitrate exposures and stomach cancer frequency. International Journal of Epidemiology 10, 5762.

A Aschengrau , S Zierler & A Cohen (1989) Quality of community water and the occurrence of spontaneous abortion. Archives of Environmental Health 44, 283290.

H Bartsch , H Ohshima & B Pignatelli (1988) Inhibitors of endogenous nitrosation. Mechanisms and implications in human cancer prevention. Mutation Research 202, 307324.

N Benjamin , F O'Driscoll , H Dougall , C Duncan , L Smith , M Golden & H McKenzie (1994) Stomach NO synthesis. Nature 368, 502.

SA Beresford (1985) Is nitrate in the drinking water associated with the risk of cancer in the urban UK?. International Journal of Epidemiology 14, 5763.

L Brunelli , JP Crow & JS Beckmann (1995) The comparative toxicity of nitric oxide and peroxynitrite to Escherichia coli. Archives of Biochemistry and Biophysics 316, 327334.

M Carnrick , BD Plois & T Klein (1946) Methaemoglobinaemia: treatment with ascorbic acid. Archives of Internal Medicine 78, 296302.

DR Cave (1996) Transmission and epidemiology of Helicobacter pylori. American Journal of Medicine 100, 12S17S.

HH Comly (1945) Cyanosis in infants caused by nitrates in well water. Journal of the American Medical Association 129, 112116.

D Corella , P Cortina , M Guillen & JI Gonzalez (1996) Dietary habits and geographic variation in stomach cancer mortality in Spain. European Journal of Cancer Prevention 5, 249257.

JM Davies (1980) Stomach cancer mortality in Worksop and other Nottinghamshire mining towns. British Journal of Cancer 41, 438445.

MJ Davies & T Thomas (1981) The pathological basis and microanatomy of occlusive thrombus formation in human coronary arteries. Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences 294, 225229.

AJ de Belder , R MacAllister , MW Radomski , S Moncada & PJ Vallance (1994) Effects of S-nitroso-glutathione in the human forearm circulation: evidence for selective inhibition of platelet activation. Cardiovascular Research 28, 691694.

MA DeGroote , D Granger , Y Xu , G Campbell , P Prince & FC Fang (1995) Genetic and redox determinants of nitric oxide cytotoxicity in a Salmonella typhimurium model. Proceedings of the National Academy of Sciences USA 92, 63996403.

KM Desai , WC Sessa & JR Vane (1991) Involvement of nitric oxide in the reflex relaxation of the stomach to accommodate food or fluid. Nature 351, 477479.

HT Dougall , L Smith , C Duncan & N Benjamin (1995) The effect of amoxycillin on salivary nitrite concentrations: an important mechanism of adverse reactions?. British Journal of Clinical Pharmacology 39, 460462.

C Duncan , H Dougall , P Johnston , S Green , R Brogan , C Leifert , LM Smith , M Golden & N Benjamin (1995) Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate. Nature Medicine 1, 546551.

RS Dykhuizen , A Fraser , H McKenzie , M Golden , C Leifert & N Benjamin (1998) Helicobacter pylori is killed by nitrite under acidic conditions. Gut 42, 334337.

D Forman , SA Al-Dabbagh & R Doll (1985) Nitrates, nitrites and gastric cancer in Great Britain. Nature 313, 620625.

RF Furchgott & JV Zawadzki (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288, 373376.

JM Gaziano , JE Manson , LG Branch , GA Colditz , WC Willett & JE Buring (1995) A prospective study of consumption of carotenoids in fruits and vegetables and decreased cardiovascular mortality in the elderly. Annals of Epidemiology 5, 255260.

DA Geller , PD Freeswick , D Nguyen , AK Nussler , M Di Silvio , RA Shapiro , SC Way , RL Simmons & TP Billiar (1994) Differential induction of nitric oxide synthase in hepatocytes during endotoxaemia and the acute phase response. Archives of Surgery 129, 169171.

BR Goldin & SL Gorbach (1996) Phytoestrogens: possible role in preventing human disease. Nutrition 12, 216217.

CA Gonzalez , JM Sanz , G Marcos , S Pita , E Brullet , E Saigi , A Badia & E Riboli (1991) Dietary factors and stomach cancer in Spain: a multi-centre case–control study. International Journal of Cancer 49, 513519.

MJ Hill , GM Hawksworth & G Tattersall (1973) Bacteria, nitrosamines and cancer. British Journal of Cancer 28, 562567.

N Hogg , VM Darley-Usmar , MT Wilson & S Moncada (1992) Production of hydroxyl radicals from the simultaneous generation of superoxide and nitric oxide. Biochemical Journal 281, 419424.

N Inui , N Yoshisuke , M Taketomi & M Mori (1979) Transplacental action of sodium nitrite on embryonic cells of Syrian Golden Hamster. Mutation Research 66, 149158.

OM Jensen (1982) Nitrate in drinking water and cancer in northern Jutland, Denmark, with special to stomach cancer. Ecotoxicology and Environmental Safety 6, 258267.

CJ Johnson & BC Kross (1990) Continuing importance of nitrate contamination of groundwater and wells in rural areas. American Journal of Industrial Medicine 18, 449456.

TJA Key , M Thorogood , PN Appleby & ML Burr (1996) Dietary habits and mortality in 11 000 vegetarians and health conscious people: results of a 17 year follow up. British Medical Journal 313, 775778.

TM Knight , D Forman , SA Al-Dabbagh & R Doll (1987) Estimation of dietary intake of nitrate and nitrite in Great Britain. Food and Chemical Toxicology 25, 277285.

TM Knight , D Forman , R Piratsu , P Comba , R Iannarilli , PL Cocco , G Angotzi , E Ninu & S Schierano (1990) Nitrate and nitrite exposure in Italian populations with different gastric cancer rates. International Journal of Epidemiology 19, 510515.

H Low (1974) Nitroso compounds: safety and public health. Archives of Environmental Health 29, 256260.

JON Lundberg , E Weitzberg , JM Lundberg & K Alving (1994) Intragastric nitric oxide production in humans: measurements in expelled air. Gut 35, 15431546.

G McKnight , LM Smith , RS Drummond , CW Duncan , MNH Golden & N Benjamin (1997) The chemical synthesis of nitric oxide in the stomach from dietary nitrate in man. Gut 40, 211214.

PN Magee & JM Barnes (1967) Carcinogenic nitroso compounds. Advances in Cancer Research 10, 163246.

RN Neal , SO Brijj , RCB Slack , CJ Hawkey & RFA Logan (1994) Recent treatment with H2 antagonists and antibiotics and gastric surgery as risk factors for salmonella infection. British Medical Journal 308, 176.

WE Philips (1971) Naturally occurring nitrate and nitrite in foods in relation to infant methaemoglobinaemia. Food and Cosmetics Toxicology 9, 219228.

JM Pique , BJR Whittle & JV Esplugues (1989) The vasodilator role of endogenous nitric oxide in the rat gastric microcirculation. European Journal of Pharmacology 174, 293296.

D Pobel , E Riboli , J Cornee , B Hemon & M Guyader (1995) Nitrosamine, nitrate and nitrite in relation to gastric cancer: a case control study in Marseille, France. European Journal of Epidemiology 11, 6773.

JJ Rademacher , TB Young & MS Kanarek (1992) Gastric cancer mortality and nitrate levels in Wisconsin drinking water. Archives of Environmental Health 47, 292294.

MW Radomski , RMJ Palmer & S Moncada (1990) An l-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proceedings of the National Academy of Sciences USA 87, 51935197.

MW Radomski , RM Palmer & S Moncada (1991) Modulation of platelet aggregation by an l-arginine–nitric oxide pathway. Trends in Pharmacological Sciences 12, 8788.

MW Radomski , DD Rees , A Dutra & S Moncada (1992) S-nitroso-glutathione inhibits platelet activation in vitro and in vivo. British Journal of Pharmacology 107, 745749.

T Sasaki & K Matano (1979) Formation of nitrite from nitrate at the dorsum linguae. Journal of the Food Hygiene Society of Japan 20, 363369.

NP Sen , DC Smith & L Schwinghamer (1969) Formation of N-nitrosamines from secondary amines and nitrate in human and animal gastric juice. Food and Cosmetics Toxicology 7, 301307.

GM Sobala , B Pignatelli , CJ Schorah & H Bartsch (1991) Levels of nitrite, nitrate, N-nitroso compounds, ascorbic acid and total bile acids in gastric juice of patients with and without precancerous conditions of the stomach. Carcinogenesis 12, 193198.

GM Sobala , CJ Schorah , M Sanderson , MF Dixon , DS Tompkins , P Godwin & AT Axon (1989) Ascorbic acid in the human stomach. Gastroenterology 97, 257363.

B Spiegelhalder , G Eisenbrand & R Preussmann (1976) Influence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compounds. Food and Cosmetics Toxicology 14, 545548.

JS Stamler , DI Simon , JA Osborne , ME Mullins , O Jaraki , T Michel , DJ Singel & J Loscalzo (1992) S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proceedings of the National Academy of Sciences USA 89, 444448.

SR Tannenbaum , M Weisman & D Fett (1976) The effect of nitrate intake on nitrite formation in human saliva. Food and Cosmetics Toxicology 14, 549552.

J Tenuovo & KK Makinen (1976) Concentration of thiocyanate and ionizable iodine in saliva of smokers and nonsmokers. Journal of Dental Research 55, 661663.

AM Walker , H Jick & J Porter (1979) Drug-related superinfection in hospitalised patients. Journal of the American Medical Association 242, 12731275.

DA Wink , KS Kasprzak , CM Maragos , RK Elespuru , M Misra , TM Dunams , TA Cebula , WH Koch , AW Andrews , JS Allen & LK Keefer (1991) DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science 254, 10011003.

G Xu , P Song & PI Reed (1992) The relationship between gastric mucosal changes and nitrate intake via drinking water in a high-risk population for gastric cancer in Moping County, China. European Journal of Cancer Prevention 1, 437443.

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British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
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