This article examines the relationship between dietary nitrates and human health.
Nitrates, which can be found in green leafy vegetables, beetroot and other plant foods, have emerged as a subject of considerable interest because of their potential therapeutic and ergogenic benefits for cardiovascular, oral, neurocognitive and metabolic health, as well as athletic performance.
However, the evidence appears to be contradictory, as high intake of nitrates has also been associated with an increased risk of cancer, particularly in the gastrointestinal tract, as well as other diseases such as thyroid disease, birth defects and infant methemoglobulinemia.

NITRATES, NITRITES AND POSITIVE HEALTH EFFECTS
Nitrates are abundant in the natural environment, especially in plants. Leafy greens such as rocket, spinach, lettuce and chard, as well as root vegetables such as beetroot and radish, contain high amounts of nitrates, often in the range of 1000-2000+ mg/kg. These nitrate-rich vegetables can often also contain small amounts of nitrites, along with an abundance of fibre, vitamins, minerals and phytochemicals, including polyphenols.
Regular consumption of fruits and vegetables, especially nitrate-rich green leafy vegetables, is inversely associated with coronary heart disease, stroke, type 2 diabetes and also mortality. The cardiometabolic benefits of dietary nitrates, including their effect on blood pressure, have also been reported after ingestion of nitrates not derived from plants, such as potassium nitrate.
However, the cardiometabolic benefits of dietary nitrates are more obvious when consumed from plant sources, as we see in diets high in nitrates (e.g.: rich in green leafy vegetables, beetroot juice, etc.).
Also, compounds such as S-nitrosothiols and nitrolipids may have beneficial effects, such as regulating oxygen delivery and exerting anti-inflammatory effects.

NITRATES, NITRITES AND NEGATIVE HEALTH EFFECTS
Nitrate and nitrite salts, including sodium nitrate and nitrite and potassium nitrate and nitrite (E249/E250/E251/E252), are food additives currently authorised for use in the European Union.
These preservatives are added to cured meats such as bacon, sausages and ham, as well as to cheeses, to improve flavour and colour, prevent microbial growth and extend shelf life. The production of nitric oxide from nitrates kills bacteria, preventing their growth and accumulation, thus delaying meat rotting.
However, the exogenous metabolism of nitrates added as a preservative increases the proportion of available nitrite and preformed nitrosamines, which are carcinogenic, compared to foods naturally rich in nitrates where the formation of nitrite and other nitrate metabolites is prevented by high concentrations of antioxidants and polyphenols, such as in vegetables.
It is estimated that foods containing nitrate/nitrite preservatives, such as processed meats and cheeses, although providing only 6-8% of total dietary nitrate, provide a large 35-39% of total dietary nitrite intake.
Indeed, the higher ratio of preformed nitrite and secondary reactive nitrogen species seems to favour the formation of carcinogenic N-nitroso compounds rather than the formation of nitric oxide, even when the total nitrate load is lower.
Ingestion of preformed nitrosamines, including N-nitrosodimethylamine (NDMA), is consistently associated with increased risks of gastrointestinal and other cancers.

In addition, processed meats and cheeses lack key antioxidants and phytochemicals that inhibit further nitrosamine formation from available nitrites. As a matter of a fact, a recent study showed that the addition of plant phytochemicals in the processing of red meat can reduce the formation of N-nitroso compounds, even without a simultaneous reduction in the use of nitrite preservatives.
Consequently, high consumption of red and processed meat is associated with more than 30% increased risk of colorectal cancer, and an increased risk of breast, endometrial, colorectal, rectal, lung and kidney cancer.
High intakes of nitrates and nitrites from animal sources have also been found to be associated with an increased risk of gastric cancer, type 2 diabetes mellitus, non-alcoholic steatohepatitis, Alzheimer's disease and cardiovascular disease-related mortality.
Taken together, these data suggest that consumption of foods containing nitrate/nitrite additives, particularly of animal origin, adversely modifies nitrate metabolism, promoting the formation of carcinogenic N-nitroso compounds and leading to impaired cardiometabolic health.
Other food processing methods have also been shown to promote the exogenous formation of N-nitroso compounds and thus may contribute to the risk of nitrate-related cancer, such as smoked, salted and cured foods.
In addition, frequent consumption of pickled vegetables, including nitrate-rich vegetables such as cabbage, is associated with >50% greater risk of developing gastric cancer.
Once again, this appears to be linked to the concentration of preformed N-nitroso compounds produced during the process, despite the fact that the antioxidant capacity of these foods is retained to some extent.
Traditional methods of packaging liquid vegetables that leave them in a jar for weeks or months to ferment facilitate the growth of microorganisms that can lead to the production of N-nitroso compounds and mycotoxins.
Drinking water can also represent a significant source of dietary nitrates due to contamination from inorganic or manure-based agricultural fertilisers entering surface and groundwater from waste run-off and/or human or animal waste.
Industrial areas often report nitrate concentrations in rainwater of up to ~5 mg/L; however, in most countries the concentration of nitrate in drinking water does not exceed 10 mg/L, which is still significantly lower than the current US and European limits of 45 mg/L and 50 mg/L, respectively, and contributes less than 14 % of total intake.
Nitrates in drinking water have been linked (although not conclusively) to the development of infantile methemoglobulinemia, also known as blue baby syndrome, as well as with cancer of the colon and the stomach, although the carcinogenic potential of nitrates in drinking water is not as clear as nitrates in processed meat.

CONCLUSIONS
- In conclusion, we note that interestingly, beneficial effects are often observed when nitrate is consumed from plant sources, while adverse effects are more often associated with nitrate intake from drinking water and processed meats.
- The presence of antioxidants and polyphenols in fruits and vegetables helps to shift the conversion of nitrites to nitric oxide formation and away from the production of potentially carcinogenic N-nitroso compounds.
- On the other hand, the presence of nitrosatable precursors and heme in (processed) red meat promotes nitrification and the formation of carcinogenic N-nitroso compounds, while exogenous metabolism of nitrate and nitrite salts increases the proportion of available nitrite and preformed nitrosamines, which are carcinogenic.
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Sources/bibliography/more reading:
- Zurbau A, Au-Yeung F, Blanco Mejia S, Khan TA, Vuksan V, Jovanovski E, Leiter LA, Kendall CWC, Jenkins DJA, Sievenpiper JL. Relation of Different Fruit and Vegetable Sources With Incident Cardiovascular Outcomes: a Systematic Review and Meta-Analysis of Prospective Cohort Studies. j Am Heart Assoc. 2020 Oct 20;9(19):e017728. doi: 10.1161/JAHA.120..017728. epub 2020 Oct 1. PMID: 33000670; PMCID: PMC7792377.
- Schwingshackl L, Hoffmann G, Lampousi AM, Knüppel S, Iqbal K, Schwedhelm C, Bechthold A, Schlesinger S, Boeing H. Food groups and risk of type 2 diabetes mellitus: a systematic review and meta-analysis of prospective studies. Eur J Epidemiol. 2017 May;32(5):363-375. doi: 10.1007/s10654-017-0246-y. Epub 2017 Apr 10. PMID: 28397016; PMCID: PMC5506108.
- Yip CSC, Chan W, Fielding R. The Associations of Fruit and Vegetable Intakes with Burden of Diseases: a Systematic Review of Meta-Analyses. J Acad Nutr Diet. 2019 Mar;119(3):464-481. doi: 10.1016/j.jand.2018.11.007. Epub 2019 Jan 11. PMID: 30639206.
- Wang DD, Li Y, Bhupathiraju SN, Rosner BA, Sun Q, Giovannucci EL, Rimm EB, Manson JE, Willett WC, Stampfer MJ, Hu FB. Fruit and Vegetable Intake and Mortality: Results From 2 Prospective Cohort Studies of US Men and Women and a Meta-Analysis of 26 Cohort Studies. Circulation. 2021 Apr 27;143(17):1642-1654. doi: 10.1161/CIRCULATIONAHA.120..048996. epub 2021 Mar 1. PMID: 33641343; PMCID: PMC8084888.
- McDonagh STJ, Wylie LJ, Webster JMA, Vanhatalo A, Jones AM. Influence of dietary nitrate food forms on nitrate metabolism and blood pressure in healthy normotensive adults. Nitric Oxide. 2018 Jan 30;72:66-74. doi: 10.1016/j.niox.2017.12.001. epub 2017 Dec 6. PMID: 29223585.
- Zhang Y, Zhang H, An W, Li D, Qin L. Regulatory effect of dietary nitrate on blood pressure: a meta-analysis of randomized controlled trials. Food Funct. 2023 Feb 21;14(4):1839-1850. doi: 10.1039/d2fo03140j. PMID: 36740972.
- Behrens CE Jr, Ahmed K, Ricart K, Linder B, Fernández J, Bertrand B, Patel RP, Fisher G. Acute beetroot juice supplementation improves exercise tolerance and cycling efficiency in adults with obesity. Physiol Rep. 2020 Oct;8(19):e14574. doi: 10.14814/phy2.14574. PMID: 33063953; PMCID: PMC7556310.
- Pateiro M, Domínguez R, Munekata PES, Nieto G, Bangar SP, Dhama K, Lorenzo JM. Bioactive Compounds from Leaf Vegetables as Preservatives. Foods. 2023 Feb 2;12(3):637. doi: 10.3390/foods12030637. PMID: 36766166; PMCID: PMC9914076.
- Pobel D, Riboli E, Cornée J, Hémon B, Guyader M. Nitrosamine, nitrate and nitrite in relation to gastric cancer: a case-control study in Marseille, France. Eur J Epidemiol. 1995 Feb;11(1):67-73. doi: 10.1007/BF01719947. PMID: 7489775.
- De Stefani E, Boffetta P, Mendilaharsu M, Carzoglio J, Deneo-Pellegrini H. Dietary nitrosamines, heterocyclic amines, and risk of gastric cancer: a case-control study in Uruguay. Nutr Cancer. 1998;30(2):158-62. doi: 10.1080/01635589809514656. PMID: 9589435.
- Loh YH, Jakszyn P, Luben RN, Mulligan AA, Mitrou PN, Khaw KT. N-nitroso compounds and cancer incidence: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study. Am J Clin Nutr. 2011 May;93(5):1053-61. doi: 10.3945/ajcn.111.012377. Epub 2011 Mar 23. PMID: 21430112.
- Keszei AP, Goldbohm RA, Schouten LJ, Jakszyn P, van den Brandt PA. Dietary N-nitroso compounds, endogenous nitrosation, and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study. Am J Clin Nutr. 2013 Jan;97(1):135-46. doi: 10.3945/ajcn.112.043885. Epub 2012 Nov 28. PMID: 23193003.
- van Breda SG, Mathijs K, Pieters HJ, Pieters HJ, Sági-Kiss V, Kuhnle GG, Georgiadis P, Saccani G, Parolari G, Virgili R, Sinha R, Hemke G, Hung Y, Verbeke W, Masclee AA, Vleugels-Simon CB, van Bodegraven AA, de Kok TM; PHYTOME consortium. Replacement of Nitrite in Meat Products by Natural Bioactive Compounds Results in Reduced Exposure to N-Nitroso Compounds: The PHYTOME Project. Mol Nutr Food Res. 2021 Oct;65(20):e2001214. doi: 10.1002/mnfr.202001214. epub 2021 Aug 27. PMID: 34382747; PMCID: PMC8530897.
- Norat T, Lukanova A, Ferrari P, Riboli E. Meat consumption and colorectal cancer risk: dose-response meta-analysis of epidemiological studies. Int J Cancer. 2002 Mar 10;98(2):241-56. doi: 10.1002/ijc.10126. PMID: 11857415.
- Farvid MS, Sidahmed E, Spence ND, Mante Angua K, Rosner BA, Barnett JB. Consumption of red meat and processed meat and cancer incidence: a systematic review and meta-analysis of prospective studies. Eur J Epidemiol. 2021 Sep;36(9):937-951. doi: 10.1007/s10654-021-00741-9. Epub 2021 Aug 29. PMID: 34455534.
- Hernández-Ramírez RU, Galván-Portillo MV, Ward MH, Agudo A, González CA, Oñate-Ocaña LF, Herrera-Goepfert R, Palma-Coca O, López-Carrillo L. Dietary intake of polyphenols, nitrate and nitrite and gastric cancer risk in Mexico City. Int J Cancer. 2009 Sep 15;125(6):1424-30. doi: 10.1002/ijc.24454. PMID: 19449378; PMCID: PMC2787087.
- Tong M, Neusner A, Longato L, Lawton M, Wands JR, de la Monte SM. Nitrosamine exposure causes insulin resistance diseases: relevance to type 2 diabetes mellitus, non-alcoholic steatohepatitis, and Alzheimer's disease. J Alzheimers Dis. 2009;17(4):827-44. PMID: 20387270; PMCID: PMC2952429.
- Bondonno NP, Pokharel P, Bondonno CP, Erichsen DW, Zhong L, Schullehner J, Frederiksen K, Kyrø C, Hendriksen PF, Hodgson JM, Dalgaard F, Blekkenhorst LC, Raaschou-Nielsen O, Sigsgaard T, Dahm CC, Tjønneland A, Olsen A. Source-specific nitrate intake and all-cause mortality in the Danish Diet, Cancer, and Health Study. Eur J Epidemiol. 2024 May 28. doi: 10.1007/s10654-024-01133-5. Epub ahead of print. PMID: 38802612.
- Ren JS, Kamangar F, Forman D, Islami F. Pickled food and risk of gastric cancer-a systematic review and meta-analysis of English and Chinese literature. Cancer Epidemiol Biomarkers Prev. 2012 Jun;21(6):905-15. doi: 10.1158/1055-9965.EPI-12-0202. epub 2012 Apr 12. PMID: 22499775.
- Fan AM, Steinberg VE. Health implications of nitrate and nitrite in drinking water: an update on methemoglobinemia occurrence and reproductive and developmental toxicity. Regul Toxicol Pharmacol. 1996 Feb;23(1 Pt 1):35-43. doi: 10.1006/rtph.1996.0006. PMID: 8628918.
- Essien EE, Said Abasse K, Côté A, Mohamed KS, Baig MMFA, Habib M, Naveed M, Yu X, Xie W, Jinfang S, Abbas M. Drinking-water nitrate and cancer risk: a systematic review and meta-analysis. Arch Environ Occup Health. 2022;77(1):51-67. doi: 10.1080/19338244.2020.1842313. Epub 2020 Nov 3. PMID: 33138742.
- Picetti R, Deeney M, Pastorino S, Miller MR, Shah A, Leon DA, Dangour AD, Green R. Nitrate and nitrite contamination in drinking water and cancer risk: a systematic review with meta-analysis. Environ Res. 2022 Jul;210:112988. doi: 10.1016/j.envres.2022.112988. doi: 10.1016/j.envres.2022.112988. Epub 2022 Feb 22. PMID: 35217009.
- Bowles EF, Burleigh M, Mira A, Van Breda SGJ, Weitzberg E, Rosier BT. Nitrate: 'the source makes the poison'. Crit Rev Food Sci Nutr. 2024 Aug 30:1-27. doi: 10.1080/10408398.2024.2395488. PMID: 39213282.