Health Stream Literature Summary - Issue 50 - June 2008

When does nitrate become a risk for humans?
Powlson, D.S., Addiscott, T.M., Benjamin, N., Cassman, K.G., De Kok, T.M., Van Grinsven, H., L'Hirondel, J.-L., Avery, A.A. and Van Kessel, C. (2008) Journal of Environmental Quality, 37(2); 291-295.

There is still substantial disagreement among scientists over the question of whether nitrate is harmful to humans and whether the current limits for nitrate concentration in drinking water are justified by science. The WHO limit for nitrate in the EU is 50 mg of nitrate /L and in the USA 44 mg /L. A symposium was held on "The Nitrogen Cycle and Human Health" to address these questions. This article presents the issues discussed at the symposium and during subsequent email exchanges between some participants.

There are two main health issues associated with nitrate and human health: infant methaemoglobinaemia, (also known as blue baby syndrome) and cancer of the digestive tract. Studies conducted in the 1940s attributed the incidence of methaemoglobinaemia in babies to nitrate concentrations in rural well water used for making up formula milk replacement. A re-evaluation of these original studies indicated that cases of methaemoglobinaemia always occurred when wells were contaminated with human or animal excrement and that the well water contained appreciable numbers of bacteria and high concentrations of nitrate. Some scientists now believe that many early cases of infant methaemoglobinaemia that were attributed at the time to nitrate in well water were in fact caused by gastroenteritis due to the presence of bacteria rather than nitrate.

There have been about 50 epidemiological studies since 1973 investigating the link between nitrate and stomach cancer incidence and mortality in humans. On the basis of the evidence the Chief Medical Officer in Britain, the Scientific Committee for Food in Europe and the Subcommittee on Nitrate and Nitrite in Drinking Water in the USA all concluded that there is no convincing association between nitrate in drinking water and stomach cancer incidence and mortality.

There is evidence emerging of a possible benefit of nitrate in cardiovascular health. A study of the coronaries of rats provided with sodium nitrate-containing water for 18 months found that the coronaries became thinner and more dilated that the coronaries of the rats in the control group. One study in healthy young human volunteers showed a short-term increase in dietary nitrate reduced diastolic blood pressure. Nitrate is made in the human body with the rate of production influenced by factors such as exercise. It has been show in recent years that body cells produce nitric oxide from the amino acid L-arginine and that this production it crucial to maintain normal blood circulation and protection from infection. Nitrate can also be chemically reduced to nitric oxide in the stomach where it can assist in the destruction of swallowed pathogens that can cause gastroenteritis.

A recent literature review suggests that there are certain subgroups in the population that may be more susceptible than others to adverse health effects of nitrate. It appears that those individuals with increased rates of endogenous formation of carcinogenic N-nitroso compounds are likely to be susceptible. Factors known to alter susceptibility to the development of cancer in the digestive system include: inflammatory bowel diseases, high red meat consumption, amine-rich diets, smoking and dietary intake of inhibitors of endogenous nitrosation (e.g. polyphenols and vitamin C). It is argued that such susceptible subpopulations should be considered when trying to make a risk-benefit analysis for the intake of nitrate.

Levels of nitrate and other N-containing species have increased in many parts of the ecosystem due to the increased use of fertilisers and combustion of fossil fuels. The environmental impacts of reactive N compounds are serious, so therefore an integrated systems management approach is required to better match the amount and timing of N fertiliser application to the actual crop N demand in time and space. The adverse environmental impact of reactive N species needs to be considered as they have increased over the last few decades and this trend appears to be continuing. Some of these molecules such as nitrogen oxides come from combustion of fossil fuels in automobiles and power plants however the main source is through the cultivation of nitrogen-fixing crops and the manufacture and use of N fertilisers. N enrichment causes changes to terrestrial and aquatic ecosystems with indirect health effects.

The authors conclude that there is an urgent need to re-examine the scientific validity of current drinking water standards for nitrate. In particular efforts should be made to examine susceptible population subgroups, develop biomarkers for endogenous nitrosation, and methods for quantifying mediating factors. There is also a need for defining water quality standards for protection of aquatic ecosystems.