ALIA - Alimentation et industries alimentaires

Strategies of prevention of colon carcinogenesis in production and processing of meats – SECURIVIANDE

Limit the risk of colon cancer associated with excessive consumption of meat products

Change the production of meat products to reduce the risk of colon cancer associated with a high consumption: a study from the cell to the consumer

Define an alternative to limitation of consumption

Colorectal cancer is the leading cause of cancer death among non-smokers in France, every day, 100 cases are detected, and 45 people die. Epidemiology shows that excessive consumption of red meat, porcessed meat and other meat products is a risk factor for colon cancer. The recommendations of the WCRF-2007 are accurate and strong: to limit consumption of red meat (less than 300 g / week at the population level) and avoid processed meat. These recommendations, important for public health, lead to limit or exclude the consumption of red meat and meat products, but they provide essential nutrients hard to find elsewhere (haem iron, vitamin B12 etc. ... ).<br />It therefore seems important to invest in preventive strategies to decrease the incidence of colorectal cancer without getting to stop eating meat. According to the results of a previous project, HemeCancer (ANR-PNRA), these strategies can be based (i) for industrial, on process changes of processed and (ii) for the consumer, on specific dietary recommendations (combination of complementary foods). This project aims to establish meat production that bringing benefits in terms of safety of meat products, compared to the risk of colorectal carcinogenesis.<br />For this project, hypothesis is that heme iron from meat increases lipid peroxidation, nitrosylation, and cytotoxicity of colonic contents: aldehydes and N-nitroso compounds produced are at the origin of tumor promotion. This project will therefore test the formulations and methods of processing of meat products from beef and pork, limiting the formation of peroxides, N-nitroso compounds in the gut or cytotoxic.

The project SecuriViande is organized around 4 steps:
-the first is to produce meat and cured meats models (n = 32) with manufacturing process modified to potentially modify the risk of promotion of colon cancer. Once the meat produced, impact on biomarkers of peroxidation and nitrosylation will be assessed in rats. The most effective manufacturing process for the limitation of these two reactions will be selected for the second stage.
-The second phase will test the impact of these manufacturing process (n = 12) on the promotion of colon cancer. The most effective for minimizing the risk in comparison to an unmodified meat will be selected to be tested in humans (n = 6).
-Effect of meat products will be evaluated as the fundamental point of view to determine the mechanisms involved in the promotion of colon carcinogenesis (third step).
-Finally, to ensure the extrapolation of experimental data to humans (fourth step), we measure the effect of the 6 modified meats in healthy volunteers, to monitor (as in the animal model) the modulation of fecal biomarkers of nitrosylation and peroxidation. Finally, as these changes in manufacturing process will have an organoleptic impact, we will test acceptability by the consumer.

The first two stages of the project have been completed, and the the most significant result at this stage of project SecuriViande is the firt demonstration in the experimental model that consumption of meat or processe meat increases colorectal carcinogenesis at the tumoral level. More importantly, we demonstrated that adding grenade or tocopherol during processed meat processing was protective, or modifying red meat with marinade (grape and olive oil) limited promotion of colorectal carcinogenesis. This is the first evidence that the concept of modification of the processing of meat to decrease the risk of colorectal carcinogenesis associated with their consumption is possible. This must obviously be confirmed in human at the fecal and urinary biomarkers level(fourth stage)

If the project resulted in the identification of manufacturing process
-effective in animal models (with validation in humans at the level of biomarkers) and
-accepted by the consumer,
the final goal could be to define recommendations for change modes of production of industrial products with meat

-Presentation of the project to the two industrial sectors (red meat and cured meat)
-Presentation in congresses (Congress of Nutrition, Congress mass spectrometry)
.

Colorectal cancer is the first cause of death in non-smokers: each day one hundred new cases are detected in France and 45 of them will die within few years. Red meat and processed meat intake is clearly a risk factor for colorectal cancer, according to meta-analyses of epidemiological studies. The increase in risk is not very high (+25-30%) but WCRF-2007 panel recommendations are strong: "Limit red meat intake (300 g/week at a population level), and avoid processed meat intake". These key recommendations to improve public health could lead to a drastic reduction of meat intake, and could have dramatic economical consequences be dramatic on the processed meat pork industry and on the bovine market.
The research of preventive strategies is thus important to reduce colorectal cancer risk without eliminating any food from our plates. Two strategies can be considered: (i) industrial processes could be modified to produce healthier meat and processed meat, and (ii) consumers could adhere to specific recommendations (e.g., eating a specific protective food in the same meal as processed meat). The first suggestion would lead to production of processed meat without cancer risk, by changing food processing: the goal of this project is thus to define processing, and packaging that would improve food safety and decrease colorectal cancer risk. The central hypothesis is that heme iron in meat would increase lipoperoxidation, nitrosation and cytotoxicity of the intestinal content. Resulting aldehydes and N-nitrosated compounds would select tumor cells and promote tumor growth. The present project will thus test additives and processes to make beef and pork meat products that limit fat peroxidation, N-nitrosation, and cytotoxicity in the colon lumen. Most effective modifications will be identified in animal and cellular models, and these modifications will be validated in human volunteers. In addition, the research of molecular mechanisms should lead to new molecular biomarkers that we will use to translate results from rodents to Humans. Furthermore, the project aims to validate the acceptance of these new meat products by consumers, testing their sensory (organoleptic) properties. The project is structured in six steps: (i) beef and pork meat processing to obtain 28 beef meat products and 16 pork meat products. These products will be given to rodents to test (ii) the impact on peroxidation, cytotoxicity, nitrosylation and iron status in the colon. Following this step, six meat processes will be chosen, according to their effect on the above cited biomarkers. These six processed meats will be tested in rodents to see (iii) their effect on colorectal carcinogenesis, and (iv) their cellular and molecular mechanisms of effect. (v) Relevance of these processes will be tested in “real life” industrial workshop. Eventually, three processes will be chosen to be tested in human volunteers (vi) to check their effect on fecal peroxidation and cytotoxicity and on consumer acceptance.
This scientific project is thus part of the effort of food industry to improve continuously the safety of food products, and specifically to adapt to the recently identified cancer risk associated with meat consumption.

Project coordination

Fabrice PIERRE (Organisme de recherche)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Fleury Michon Fleury Michon
ADIV ASSOCIATION POUR LE DEVELOPPEMENT DE L'INSTITUT DE LA VIANDE
UR 1213 INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE - CENTRE DE RECHERCHE DE CLERMONT FERRAND THEIX
FICT Fédération Française des Industriels Charcutiers, Traiteurs, Transformateurs de Viandes
IFIP IFIP - INSTITUT DU PORC
UR 0370 INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE - CENTRE DE RECHERCHE DE CLERMONT FERRAND THEIX
CRNH CENTRE DE RECHERCHE EN NUTRITION HUMAINE D AUVERGNE ( CRNH)
UMR1324 INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE - CENTRE DE RECHERCHE DE DIJON
NOVALEADS

Help of the ANR 748,051 euros
Beginning and duration of the scientific project: - 48 Months

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