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NITRATE AND NITRITE SALTS AND HUMAN HEALTH

Nick Krontiris

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.).

It seems that the presence of phytochemicals, including polyphenols and antioxidants, in nitrate-rich vegetables neutralises the formation of toxic nitrogen-containing species, thus reducing the risk of carcinogenesis.

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

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