Why deli meats with nitrites are carcinogenic

Nitrite salts (potassium E249 or sodium E250 nitrites) are used as preservatives in various preparations of processed meats, in particular in deli meats.

For several years, their effects on health have been pointed out. In view of the available scientific data, there is now no longer any doubt that there is a link between consumption of nitrated deli meats and increased risk of colorectal cancer. However, it is also known that nitrite itself is not directly the cause of colorectal cancer. What happens, then, after it is added to the charcuterie? How can an initially non-carcinogenic compound be problematic?

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To understand it, we must remember the famous maxim attributed to the chemist Antoine Lavoisier: in chemistry “nothing is lost, nothing is created, everything is transformed”.

This is the case with nitrite additives: in contact with meat, they are transformed into other much more problematic compounds, reactive nitrogen species, also called “nitrosated compounds”. This seriously complicates the task in terms of health expertise and risk management…

Nitrite, real false culprit?

Nitrite, with the chemical formula NO2-, is a toxic nitrogen oxide if ingested and very toxic to the environment, as recalled its safety data sheet.

But it is not this direct toxicity that poses a problem when nitrite is added to charcuterie. Indeed, very quickly, it reacts and disappears: from the 120 mg added per kilo of ham, only 10-20% remains a few days later.

Nitrite is what is called a “reactive molecule”: it interacts with other biomolecules, such as lipids or proteins, and forms other chemically active molecules. Thus, about 80% of added nitrites in deli meats become “something else”, turning into molecules called “reactive nitrogen species”. And this, more or less quickly depending on the environment.

It is because of this ability to transform that nitrite is used as a preservative: the nitrogenous molecules produced have biological effects that destroy undesirable microorganisms which could, in large quantities, be the cause of food poisoning. . The problem is that some of these molecules, such as nitrosamines, have a strong carcinogenic potential.

Reactive nitrogen species

The members of this family are very varied, and have very different reactivities and toxicities from each other. There are, for example, molecules related to nitric oxide NO°, an essential signal molecule that regulates a very large number physiological functions in humans.

This NO° can bind to metals and metalloproteins and form heme-nitrosyl complexes, such as nitrosyl-myoglobin, which plays a crucial role in neurotransmission, control of vasodilation, platelet aggregation and immunological responses.

Other members of this family, nitrosothiols, are molecules formed by adding NO° to proteins or biomolecules, some of which, such as glutathione, play an important protective role in cells.

A third type of reactive nitrogen species are molecules capable of modifying organic molecules by causing them to undergo “nitrosation” (such as nitrogen dioxide, NO2). Finally, another category of these reactive nitrogen species consists of highly reactive molecules capable, like peroxynitrite, of modifying a wide range of biomolecules.

Document provided by the authors

Not all reactive nitrogen species have the same toxic potential, as shown in the figure above. If adducts such as nitrosothiols (green) are considered to be of low toxicity, this is not at all the case for species such as NO2 (orange) or peroxynitrite (red) at the origin of most nitrosating and oxidizing stress. cellular, and associated with a large number of pathologies, such as cancer, diabetes, cardiovascular and neurodegenerative diseases, etc.

A changing soup of molecules

These extremely reactive molecules have very short lifespans, depending on their biological environment, and are constantly reacting and transforming into each other.

We are not dealing with a series of stable and very distinct molecules, but with a chemical soup in perpetual boiling, whose reactivity and toxicity are constantly changing, and which are difficult to characterize: the identity, the the future and the impact on the organism of this multiplicity of molecules depend above all on the biological environment and history.

Not only does this “nitrogen soup” change in processed meats, but reactive nitrogen species change as they travel through the gastrointestinal tract depending on the physical, chemical and biological conditions of the organs.

Possible evolutions of various reactive nitrogen species in the gastrointestinal tract. | Document provided by the authors

But then, how to assess the risks to human health of this nitrite treatment when we do not know the nature of the products to which we are exposed, the actual quantity of each molecule, and their dangerousness?

The evaluation challenge

The difficulty lies in the standard risk assessment procedure. This is based on regulatory toxicology approaches, such as the “acceptable daily intake”. However, as we have seen, in the case of nitrites, a changing mixture of reactive molecules is generated, which complicates the quantification and qualification of exposure.

In such a situation, it is necessary to change the paradigm and no longer seek separately to identify, quantify and characterize the toxicity of molecules, which are too versatile and ephemeral. We must rather follow this soup of nitrogen and try to determine, for each tissue, for each physiological condition, its impact.

In other words, the idea is rather to follow the “fingerprint” left by the reactive nitrogen species, the marks they imprint on the tissues (oxidation, nitrosation, nitration, adducts, etc.), which are as much chemical evidence of their passage and reactivity, rather than the molecules themselves.

Thus, we will not know the exact composition of this nitrogen soup, but we will measure its toxicity directly.

Beyond this biochemist discourse, how can this knowledge be put into practice in the context of health expertise? This is the question posed by the “Risk assessment of nitrates and nitrites” working group, set up by the National Agency for Food, Environmental and Occupational Health Safety (ANSES ). In his report published in July 2022he underlines the difficulties of this exercise.

What knowledge for health expertise?

Any assessment of health risks is necessarily incomplete, temporary and requires constant readjustment. Faced with the complexity of assessing the risks due to reactive molecules, several questions arise. That of the nature of the knowledge that can and must be mobilized in the context of health expertise, in particular, is crucial.

As the reports have pointed out of the General Inspectorate of Sanitary Affairs (IGAS) or of ANSES’s Scientific Councilit is essential to integrate the most recent academic knowledge into the expertise process.

We must also be wary of the misinterpretations that could be made of these complex and scientifically demanding reports, so as not to set up standardized regulatory methods that would prove to be inadequate in the face of the complexity of biological systems.

The case of nitro additives in processed meats is a good illustration of these problems. As with all reactive molecules used as additives, it is impossible to conduct a “standard” risk assessment. There is indeed a strong risk of confusion between the intrinsic toxicity of nitrite and the carcinogenicity of charcuterie. However, as explained previously, the problem, in the case of the risk of colorectal cancer, is not the nitrite, but the molecules which result from its addition to meat-based preparations. Risk management policies should therefore not be based on controlling exposure to nitrite (by the acceptable daily intake), because this is a false culprit, and therefore a perfect decoy.

This tension between academic knowledge and public expertise brings to the fore the question of the level of proof necessary to enlighten and guide public decision-making.

In the future, further studies may yield new scientific data on the effects of all nitroso compounds that are formed both in deli meats and in the body after consumption. In the meantime, it is important to discuss the nature and relevance of the scientific elements available and brought to the attention of the public authorities.

Risk managers must be informed that, in this specific case, epidemiological approaches constitute the highest possible level of evidence to guide public action.

This article is republished from The Conversation sous licence Creative Commons. Lire l’article original.

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