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Nitrite Prime Suspect in Processed Meat Carcinogenesis

Many questions have remained unanswered in a long-standing debate over the cancer risk attributable to eating meat. For instance: Does the risk apply to red as well as processed meats? Are all types of processed meat a potential hazard? How much needs to be eaten to impart a significant risk? What is responsible for the increased risk? However, there may be new clarity on the issue resulting from a study by Queen's University Belfast demonstrating how too much nitrite-cured meat imparts "a clear risk of colorectal cancer".

The researchers noted that colorectal cancer (CRC) is the third most prevalent malignancy worldwide and the second most prevalent in Europe. Around 5% of cases are attributable to familial adenomatous polyposis, but the rest are believed to be influenced by environmental factors. Diet is "a leading candidate in the search for causes of CRC", and "an important modifiable risk factor," they said.

Public Health Advice at Odds With Reality

"Current public health advice treats all processed meat equally, when in reality there are many differences in their composition," said the researchers. "Most notably, there is the addition of sodium nitrite as a preservative, which is present in some products and not in others." For example, nitrites are not traditionally an ingredient in the manufacture of British/Irish sausages, but are more common in continental European sausages.

While sodium nitrite uniquely prevents the growth of Clostridium Botulinum, and contributes to the colour and taste of processed meat, ingested nitrite has the potential to form N-Nitroso compounds (NOC) including nitrosamines, some of which are known to be carcinogenic. NOCs have been proposed to be involved in the aetiology of several types of cancer, particularly those in the gastrointestinal tract.

As well as being incriminated in colorectal cancer, red and processed meats have been implicated in dementia, cardiovascular and specifically ischaemic heart disease. The International Agency for Research on Cancer (IARC) has advised consumers to avoid consuming processed meat, and to limit the quantity of red meat consumed.

The World Health Organisation (WHO) baldly declared in 2015 that all processed meats – which include bacon, sausages, ham,prosciutto, hot dogs (frankfurters), corned beef, biltong or beef jerky, and salami – cause cancer. It specified that 50g of processed meat a day - less than two slices of bacon - increased the chance of CRC by 18%. However, in classifying all processed meat as a carcinogen, it did not distinguish between processed meats containing nitrites and those without.

'Confusing' situation for Industry and Public

This was "confusing" for the food industry and the public, according to a 2019 paper, also from Queen's University Belfast, that found the evidence of a link with CRC jumped from around half of all studies included in a meta-analysis to just under two-thirds (65%) when only processed meats containing the preservative sodium nitrite were included. The researchers said there was "a need to define the health risk of both types of processed meat separately".

For the new study, published in npj Science of Food, they attempted to dissect the difference in an animal model. They noted that previous pre-clinical studies mostly used cancer that was chemically induced and not spontaneous, and that animal studies reporting significant causative effects on CRC supplied ≥50% processed meat in the diet. "This does not reflect typical human consumption, and therefore further studies employing more realistic levels of processed meat are required."

For the latest investigations, scientists studied mice with adenomatous polyposis coli (APC) multiple intestinal neoplasia (min) to assess how the CRC pathology and metabolic status were perturbed following 8 weeks' consumption of pork meat representing 15% dietary inclusions of either nitrite-free pork, nitrite-free sausage, or nitrite-containing sausage (frankfurter) versus a parallel control group fed 100% normal chow. The dietary options were designed to reflect real-world human food choices, and directly compared commercially available pork products on an equivalent gram-for-gram basis.

Nitrite Diet Led to More Tumours

The authors reported that after 8 weeks, the mice consuming the nitrite-containing frankfurter diet had 53% more (P = 0.014) gastrointestinal tumours than control mice, although aberrant crypt foci and mucin deplin foci did not differ. Urine and serum lipid peroxidation markers were 59% (P = 0.001) and 108% (P = 0.001) higher, respectively, in the nitrite frankfurter group. Gut dysbiosis was evident in these mice, the researchers said, with comparably fewer Bacteriodes and more Firmicutes. Fasting serum levels of trimethylamine N-oxide and numerous triglycerides were elevated. Various serum phosphotidylcholine species were decreased.

The researchers said: "These results demonstrate that nitrite-containing sausages may exacerbate the development of CRC pathology in APCMin mice to a greater extent than nitrite-free sausages, and this is associated with greater lipid peroxidation, wide-ranging metabolic alternation and gut dysbiosis."

Not All Processed Meats Carry the Same Risk

They added that the results "clearly show that not all processed meats carry the same risk of CRC development, and that the consumption of nitrite-containing processed meat exacerbates CRC pathology in a genetically predisposed murine model".

Lead author Professor Chris Elliott from the Institute for Global Food Security at Queen's University, who led the investigation into the horsemeat scandal of 2013, called on the Government to ban the use of nitrites in food in light of the study. "The results of this new study make the cancer risk associated with nitrite-cured meat even clearer. The everyday consumption of nitrite-containing bacon and ham poses a very real risk to public health."

Conservative MP and former health minister, Dr Daniel Poulter, has previously called for meat producers to use more natural alternatives to nitrite that perform its preservation function without the additional cancer risk.

Funding: Industrial partners: Studies investigating links between meat consumption and CRC are in-part supported by Agri-Food QUEST, a membership-based, industry-led Innovation Centre for agri-food business in Northern Ireland. Agri-Food QUEST is not only supported by funding from Invest Northern Ireland (InvestNI) but also were partially supported by commercial funding from: Finnebrogue Artisan, Karro Food group, and Cranswick.The study was also supported by the Bualuang ASEAN Chair Professor Fund and published in partnership with Beijing Technology and Business University.

C.T.E. declares that he is an editor for npj Science of Food, but was not involved in the journal's review of, or decisions related to, this manuscript. The remaining authors declare no competing interests.