Nitrates and Nitrites – are nitrates in food safe?

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There is a lot of public concern about nitrates in food and water and a lot of conflicting information regarding their safety for babies, children and adults. Many parents ask us if it is safe to feed children beetroot and spinach. There are two main health issues: the link between nitrate and (i) infant methaemoglobinaemia, also known as blue baby syndrome and (ii) cancers of the digestive tract. The issue is complex, so we have divided this article in two. Part I explains the background and the scientific research in some detail and Part II (coming soon) explains how this might relate to your family’s diet.

What are nitrates, nitrites and nitrosamines?

Nitrate is a naturally-occurring form of nitrogen, which is found in soil. Nitrogen is essential to all life. Nitrate is also found in man-made fertilizers and in groundwater. Plants use nitrates from the soil and many are high in inorganic nitrates and also some nitrites, particularly green leafy vegetables and root vegetables. Nitrates and nitrites are also used as preservatives, for example in the preparation of processed meats. Most exposure to nitrate and nitrite comes from naturally-occurring and endogenous sources such as saliva; the body makes nitrate (Bryan, 2012).

Nitrate itself is inert, but after ingestion (or in well water and meat treated with nitrite preservative, before ingestion) bacteria convert nitrates to nitrites. Nitrite may then be converted to other compounds such as nitric oxide or nitrosamines. Recent research suggests that nitric oxide may have numerous positive effects, including its ability to dilate the blood vessels, increase mitochondrial function (Larsen, 2011) improve athletic performance (Murphy, 2012) and lower blood pressure (Siervo, 2013). Beetroot is considered excellent for cardiovascular health (Hobbs, 2012; Tang, 2011). One Swedish study found that the conversion of nitrite to nitric oxide is greatly enhanced by Vitamin C and polyphenols, both of which are abundant in the diet (Lundberg, 2008).

Under certain conditions in the body, however, or due to cooking practices such as frying meat at high temperatures, nitrites can react with food constituents such as amines and amides to form compounds called N-nitrosamines, N-nitroso compounds (NOC) the majority of which are, or have the potential to be, carcinogenic (Tricker, 1991). A higher stomach pH results in a higher nitrate to nitrite conversion and more nitrite available to convert to NOC (Rostkowska, 1991). Children younger than 6 months tend to have higher digestive pH than older children and adults (Maffei, 1975). These differences disappear at approximately 6 months of age (McMullen, 2005).

Methemoglobinemia/Blue Baby Syndrome

The high nitrite content of well water has been linked to methemoglobinemia or ‘blue baby syndrome’, a disease that affects the blood’s ability to carry oxygen, in babies under 6 months. For this reason, many health agencies also advise parents to avoid high-nitrate vegetables like beetroot and green, leafy vegetables until a certain age, which varies by country. The American Academy of Pediatrics suggests avoiding high-nitrate vegetables before 3 months of age (Greer, 2005). In Sweden, Livsmedelsverket is more cautious, advising parents to wait until 12 months to give spinach and other greens.

The link between nitrate and methaemoglobinaemia was based on studies from the 1940s in the Midwestern USA. In part, these studies linked cases of methaemoglobinaemia in babies to nitrate concentrations in well water used to make formula milk. However, Comly (1945), who first investigated what he called “well-water methaemoglobinaemia,” found that the wells contained bacteria (which convert nitrates to nitrite) as well as nitrate. A re-evaluation of these studies showed that every case of methaemoglobinaemia occurred when wells were contaminated with human or animal excrement (Avery, 1999).

This may explain why the few human trials carried out on children and adults have not produced methemoglobinemia (Cornblath, 1948; Dejam, 2007). In the United States, only one child has been reported to have suffered nitrate poisoning from eating plant foods (Greer, 2005). The lack of evidence for nitrate as the cause of infant methemoglobinemia has called into question recommendations to avoid nutritious high-nitrate vegetables, particularly those relating to babies over the age of 6 months. It has also led scientists to give alternative explanations for the observed methemoglobinemia in infants, such as gastroenteritis caused by bacterial contamination (Addiscott, 2005; Avery, 1999; Hegesh and Shiloah, 1982; L’hirondel, 2006; Ward, 2005).

Cancer

It has also been proposed that nitrates, nitrites and NOC in foods such as fruits, vegetables and meat may be linked to cancers of the digestive tract. In humans however, the association is extremely uncertain.

Meat

Numerous studies have found an association between nitrite, nitrate or NOC from animal sources and certain types of cancer (Hernandez-Ramirez, 2009; Kim, 2007; Jakszyn, 2006; Mayne, 2001; Van Loon, 1998). A Swedish study found that foods high in NDMA, the most frequently occurring NOC in food (the study looked at bacon, side pork, sausages, ham, smoked fish, caviar and roe, light beer, medium-strong beer, strong beer, whiskey and chocolate) doubled the risk of stomach cancer but did not look at nitrate or nitrite specifically (Larsson, 2006). An earlier Finnish study found a similar link between NDMA and colorectal cancer (Knekt, 1999). The most recently published study, which was based on a study of the UK population, found that dietary NDMA was associated with certain cancers whilst dietary nitrate was not. Other studies have found links between meat and cancer but no link between nitrite or nitrate and cancer (Cross, 2011).

The World Cancer Research Fund has funded thousands of studies on the causes of cancer. In light of studies on red and processed meat (Chan et al, 2011; Rohrmann et al, 2013) and reviews into the processed meat studies, the WCRF recommends limiting red meat consumption to 500 grams per week for adults and avoiding all processed meat.

Vegetables

When it comes to vegetables, however, the vast majority of studies conclude that consumption of nitrate-rich vegetables lowers the risk of cancers of the digestive tract (Compare, 2010; Hernandez-Ramirez, 2009; Hertog, 1996; Kim, 2007; Kobayashi, 2002). This is thought to be because vegetables also contain numerous antioxidants which have been shown to modify the nitrosation process by inhibiting or blocking NOC production (Loh, 2011; Mirvish, 1995). The most important antioxidants (in their natural form in food) are thought to be Vitamin C, beta-carotene, Vitamin E and various polyphenols.

Several studies have specifically evaluated the combined effect of nitrate and/or nitrite and/or NDMA consumption and antioxidants such as Vitamin C and E on cancer risk. One found no association between cancer and nitrates or nitrites (Van Loon, 1998). Three found the highest cancer risk among those with the highest intake of nitrates/nitrites and the lowest intake of the antioxidants in fruits and vegetables which can prevent the conversion of nitrites to NOC, (Buatti, 1990; Kim, 2007; Mayne, 2001). The most recent found a positive association between dietary NDMA and certain cancers and an inverse relationship between cancer and Vitamin C intake (Loh, 2011).

A Mexican study evaluated animal sources of nitrite and nitrate separately from plant sources for the first time (Hernandez-Ramirez, 2009). It also uniquely evaluated the impact of dietary polyphenols. High consumption of nitrate and nitrite from animal sources combined with low polyphenol consumption increased the risk of stomach cancer compared with low nitrate intake from animal sources combined with high polyphenol consumption, which decreased the risk. Most important was the ratio of polyphenols to nitrate. Total nitrate intake was not linked to increased cancer risk, nor was high nitrate or nitrite consumption from vegetable sources.

The methodology of the nitrate studies has been questioned by some experts, at least in the case of stomach cancer (Bryan, 2012) and especially the studies into the safety of nitrates in drinking water (Ward, 2005). Several experts have questioned the hypothesis that nitrates and nitrites are inherently toxic (Bryan, 2012; Hord, 2009). There is great disagreement about this subject amongst experts. In “Ingested nitrate and nitrite and stomach cancer risk: an updated review” (Bryan, 2012) the authors criticize the methodology of many studies, concluding that neither nitrate nor nitrite per se has conclusively been linked to stomach cancer (although their review did not address other types of cancer of the digestive tract, or processed meat). The authors proposed that future studies should look further into other factors known to impact this area, such as Vitamin C intake, emphasizing that whilst not conclusive, the strongest data suggests salt and salted foods as risk factors and fruits and vegetables as protective (Compare, 2010; Crew, 2006; Tsugane, 2004).

Finally, it is worth noting that some experts believe that the nitrates themselves may confer benefits (Bryan, 2012; Hord, 2009; Mcknight, 1999; Tang, 2011). One review concluded that “The strength of the evidence linking the consumption of nitrate- and nitrite-containing plant foods to beneficial health effects supports the consideration of these compounds as nutrients” (Hord, 2009) whilst another found that “The collective body of evidence suggests that foods enriched in nitrite and nitrate provide significant health benefits with very little risk”.

Conclusions

In summary, it is unlikely that nitrates in vegetables alone cause methemoglobinemia in children under 6 months. They can probably be eaten safely in small quantities so long as they are not prepared with well water, although most current recommendations suggest waiting until 6 months to introduce solid foods. There is no evidence to suggest that nitrates in plant foods are harmful to babies and children over 6 months – or adults – who eat a healthy, balanced diet containing plenty of antioxidants and polyphenols.

A considerable body of research suggests that plant foods, particularly those which are high in nitrates such as spinach and beetroot, have many health benefits. The research into processed meats has produced mixed results but there is evidence to suggest that processed meat may be harmful. The World Cancer Research Fund has not been able to find a safe level of processed meat and currently advises the avoidance of all processed meat for children and adults alike.

We hope that you found our review of the evidence in this area helpful. Part II will explain in a bit more detail what this might mean for your family’s diet.

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