Top PDF IARC Monographs - Red meat and processed meat

Dietary assessment in the NIH-AARP Diet and Health Study was described in detail by Cross et al. (2010) . The study included approx- imately half a million women and men, each of whom completed a validated, self-adminis- tered, 124-item FFQ at baseline. Approximately 6 months later, cancer-free participants were mailed a risk factor questionnaire, which detailed information on meat intake and cooking pref- erences. Meat cooking method (grilled/barbe- cued, pan-fried, microwaved, and broiled) and doneness level (well done/very well done and medium/rare) were used in conjunction with the CHARRED database to estimate the intake of several HAAs. The FFQ assessed the usual frequency of consumption and portion size information of foods and drinks over the past 12  months. All types of beef, pork, and lamb were considered red meat, including bacon, beef, cold cuts, ham, hamburger, hot dogs, liver, pork, sausage, and steak. Processed meat included bacon, cold cuts (red and white meat), ham, luncheon meats (red and white meat), poultry sausage, red meat sausage, and standard hot dogs and low-fat hot dogs made from poultry. Meats added to complex food mixtures, such as pizza, chilli, lasagne, and stew, contributed to the relevant meat type. There were many notable strengths to this study. Several of these strengths were related to the FFQ, which not only contained detailed questions pertaining to the components

volume 114 of the IARC Monographs. 1 Red meat refers to unprocessed mammalian muscle meat—for example, beef, veal, pork, lamb, mutton, horse, or goat meat—including minced or frozen meat; it is usually consumed cooked. Processed meat refers to meat that has been transformed through salting, curing, fermentation, smoking, or other processes to enhance fl avour or improve preservation. Most processed meats contain pork or beef, but might also contain other red meats, poultry, off al (eg, liver), or meat byproducts such as blood.

Epidemiological evidence for the association between red and processed meat intake and colorectal cancer KEYWORDS: COLORECTAL CANCER, PROCESSED MEAT, DIETARY ADVICE, RED MEAT A perspective paper was synthesized during the workshop “How can we approach consensus on the healthiness of red meat?” held in Oslo, Norway, in November 2013 (Oostindjer et al., 2014). DE. Corpet and S. De Smet had the honour to participate in this exciting and stimulating meeting and co-signed the article. D. Demeyer was acknowledged in the article for his comments on the draft. The leading authors of the paper probably had the intention to present a balanced view of the discussions, making clear that health issues associated with the consumption of red meat are manifold. However, reaching consensus on a number of critical issues was an ambitious task. The resultant article contains some very interesting information and focuses on the role of red and processed meat in colorectal cancer development. However, not all comments from the co-authors were taken into account in the final manuscript, resulting in a scientifically incorrect statement in the abstract: “Epidemiological and mechanistic data on associations between red and processed meat intake and CRC are inconsistent…” Because of the high visibility of this abstract through many websites and journals we have to strongly object to that statement.

from their definition of processed red meats, and from conflicts of interest. In addition, Alexander et al. (2010) did not consider weak risk factors (less than 1.20) as relevant although they are significant, and would account for a large proportion of the disease burden at the population level (Brenner, Kloor, & Pox, 2014). Furthermore, each new study on meat and cancer adds to the evidence that the link is real (see e.g. Di Maso et al., 2013). We are therefore convinced that “apart from some uncertainty related to age and ethnicity, epidemiological data are consistent, although the underlying mechanisms remain unclear”. To conclude, Oostindjer et al. (2014) present a comprehensive summary of a workshop gathering a group of 23 scientists with sometimes widely different views on a problem not reflected in the main scientific background of the group. We understand that not all parts of the text can be fully accepted by all authors. However, these 23 authors doubting the overall consistency of the epidemiological evidence in the abstract seems to be “a bridge too far”. REFERENCES

Version postprint value. For physical activity (13% of missing values), a “missing class” was introduced into the models. Baseline characteristics of participants were compared across sex-specific quintiles of red and processed meat intake using χ2 tests or Fisher tests wherever appropriate. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models, with age as the primary time variable, to characterize the association between sex-specific quintiles of red meat, processed meat and total red and processed meat intake and incidence of overall, breast or prostate cancer risk (the two main cancer locations in the cohort). We confirmed that the assumptions of proportionality were satisfied through examination of the log-log (survival) vs. log-time plots. Tests for linear trend were performed using the ordinal score on sex-specific quintiles of intake. Participants contributed person-time until the date of cancer diagnosis, the date of last completed questionnaire, the date of death, or August 31 2015, whichever occurred first. For cancer site specific analysis, women who reported a cancer other than breast cancer and men who reported a cancer other than prostate cancer during the study period were censored at the date of diagnosis. Analyses were performed according to menopausal status for breast cancer analyses. For these analyses, women contributed person-time in the Cox model until their date of menopause for premenopausal breast cancer analysis or from their date of menopause for postmenopausal breast cancer analysis. Additionally, models restricted to invasive breast cancer cases (excluding in situ cases) were tested.

food industry funding; typically within ~10 years intervals. Few nation- al authorities have the resources to keep up-to-date with all the devel- opments and advances in the current food supply. Europe has its food compositional analysis in the EuroFIR database ( http://www.euro fir. org ), which contains national data from 26 countries (New Zealand and Canada being the only countries outside Europe). In order to deter- mine how red meat or processed meat is related to health or disease risk, it is crucial to have access to updated data on the composition of the consumed meat. However, there may be a large variability between different pieces of red meat, due to breed/genetics, trimming, animal feed processing and choices, geographic feed origin, age at slaughtering and others, but also sampling procedures and analytical differences. For comparisons it is important to use a representative part of the carcass, such as the minced beef trimming standardized to 14 –16% fat: this covers a large share of the edible part of the carcass (in Norway ~ 40%). It is also important to know whether the samples measured are representative for the entire country. Nutritional databases current- ly lack information about minimum and maximum values, or standard deviations of the measurements. Regarding the components measured, there is a lack of information on some nutrients in meat that may have health implications. Differentiation into inorganic iron and heme iron seems scarce (see http://nevo-online.rivm.nl/Default.aspx for an exception). Plant components (chlorophyll and polyphenols) or their metabolites are typically not included; neither are possible toxins produced for example during a suboptimal fermentation of harvested forage (see Versilovskis & De Saeger, 2010 , for an example of such a discussion). It is important that levels of present and emerging compounds suggestively linked to human diseases are all quanti fied and included in databases. This will make it more ef ficient to identify causal relationships.

increased lipid oxidation products in rodent faeces. 13 Substantial supporting mechanistic evidence was available for multiple meat components (NOC, haem iron, and HAA). Consumption of red meat and processed meat by man induces NOC formation in the digestive tract. High red meat consumption (300 or 420 g/day) increased levels of DNA adducts putatively derived from NOC in exfoliated colonocytes or rectal biopsies in two intervention studies. 19,20 Few human data, especially

tumorigenesis promotion as well as a-tocopherol, while white grape extract and carnosic acid extracted from rosemary did not. Promotion was evidenced on a surrogate end point biomarker, mucin-depleted foci. MDF, formed by dysplastic crypts devoid of mucin, have been identified in the colon of humans at high risk for colon cancer (41) . Like tumors, MDF harbor mutations in genes affecting colon carcinogenesis (Apc and K-ras) and show Wnt signaling activation (42) , a dramatic reduction of MUC2 expression (43) , and a strong activation of the inflammatory process (44) , all features suggesting that MDF are precancerous. Several rodent studies suggest that MDF are better predictors of colorectal cancer than ACF are (45) , and respond more consistently than ACF to promotion by red and processed meat and by dietary heme (9,20,39) ; this is why we focused on MDF data.

3- Nitrite and N-Nitroso Compounds (NOCs) NOCs, which are alkylating agents that can react with DNA, are produced by the reaction of nitrite and nitrogen oxides with secondary amines and N-alkylamides. Many NOCs, including nitrosamines and nitrosamides, are carcinogenic in laboratory animals. Humans can be exposed to NOCs by exogenous routes from certain processed meats (e;g., grilled bacon), smoked fish, cheeses or beers (62). In acidic conditions such as those found in processing procedures of meat, dinitrogen-, tri-, and tetraoxides can form and these are nitrosating agents. In a large-scale Finland cohort, N-nitrosodimethylamine intake from smoked and salted fish, and cured meat, was associated with CRC risk (RR=2.12, CI:1.04- 4.33), but nitrite intake was not related to risk (63). Humans can also be exposed to NOCs by endogenous routes, and a high-red meat diet leads to the endogenous synthesis of NOCs in volunteers (64). Decarboxylation of amino acids by gut bacteria yields amines and amides that can be N-nitrosated in the large bowel (65). Heme from meat strikingly increases NOC formation (66), even in the absence of colonic flora in the upper gastrointestinal tract (67). Ascorbic acid is often added to processed meat, as an antioxidant additive. Since it prevents nitrosation, it may reduce the formation of NOCs in foods and in the digestive tract (68).

This study shows that the incorporation of polyphenol rich plant extracts (pomegranate or red wine) or of a-tocopherol inhibited the promoting effect of cured meat on preneoplastic lesions in carcinogen-induced rats. If these results were confirmed in volunteers’ study, these agents might be added to meat during the curing process to make functional processed meat. This study represents an informative starting point; however, future research should address dose dependence and potential efficacy of modified meats that might induce effects ranging from protection, lack of protection to possible cancer-promoting effect at other doses. The use of the protective agents would reduce colorectal cancer risk compared with processed meat. This study also shows that fecal excretion of a specific class of nitroso compounds, nitrosyl iron was associated with tumorigenesis promotion by cured meat.

1.2- Major meta-analyses on meat and cancer In order to estimate the risk associated with meat intake, all of these studies were gathered in two major meta-analyses, whose major results are reported below (Larsson & Wolk, 2006; Norat, Lukanova, Ferrari, & Riboli, 2002). A meta- analysis is a statistical approach that gathers all data from published epidemiological studies, after exclusion of poor quality studies. Theoretically, the global result is equivalent to a single large study including all the subjects of the original studies. Due to the very high number of included subjects, even relative risks that are not far from one may be significant. In addition it enables the study of sub-groups that were too small to be analyzed in the original studies. Norat's meta-analysis gathers 23 cohort and case-control studies, selected out of 48 studies by using pre-established quality criteria (Norat, et al., 2002). Larsson's meta-analysis gathers 18 prospective studies selected out of 23, aggregating more than one million subjects (Larsson & Wolk, 2006). Both meta-analyses are rather independent from each other, because subjects included in Norat's study make only 15% of Larsson's one. The WCRF-AICR 2007 report also describes a meta-analysis based on original studies already included in Larsson's study, and whose results are very close to Larsson's ones. These three meta-analyses bring global and consistent conclusions for different types of meat: total meat intake, red meat, processed meat, and poultry meat. "Red meat" and "processed meat" definitions are tricky

We thus have demonstrated in animal studies that red meat and processed meat can promote colon carcinogenesis. As reported above, we provide several ways to prevent this toxic effect by changing the diet, the process, or additives: - Diet change: Calcium carbonate supplements bind heme iron and suppress carcinogenesis promotion in rats, and associated peroxidation biomarkers in rats and volunteers. We suggest that dairy products would produce the same effect. Other way to change diet is to reduce meat intake, following WCRF recommendations. - Process changes: Preventing the oxidation of fat during meat processing storage with an anaerobic packaging reduces ham-induced promotion. Also, omission of nitrite in curing solution suppressed ham-induced promotion. However, it will not be easy to get rid of nitrite. - Additives: α-tocopherol added to the curing- solution suppresses cured-meat promotion in rats, and associated biomarkers in human volunteers (unpublished results). Our team is still working on this issue, looking for natural antioxidant and/or anti-nitrosant agents that might be added to meat, notably plant polyphenols. Twelve molecules or extracts from fruits, leaves or rhizome have already been tested in short-term in vivo studies with biochemical endpoints. We are currently testing the most promising chemopreventive agents in a long term carcinogenesis study.

nitrite, oxidized , regarding hexanal concentration and pro-oxidant activity of processed meat ( ] Table 3 ) or TBARs and DHN-MA in rats feces and urine ( Table 3 and 4 ). These results thus do not support the hypothesis that different peroxidation levels could explain the difference in MDF promotion in rats fed dark cooked meat with nitrite, anaerobic and rats fed dark cooked meat with nitrite, oxidized . [ ] [ ] There were more MDF in rats given dark cooked meat with nitrite, oxidized than in rats given the same nitrite-free meat ( [ ] Table 4 ). Nitrites are nitrosating agents and can interact with secondary amino compounds to form N-nitroso-compounds. Parnaud et al. ( 11 52 , ) showed that rats fed fried bacon excrete 10 to 20 times more ATNC in feces than controls, but these ATNC do not initiate ACF in rats, nor do they promote ACF in azoxymethane-initiated rats. Haorah et al. showed that hot-dogs contain 10 times more ATNC than fresh red meat ( 53 ). Mice given a 18 hot-dog diet had 5 times more ATNC in feces than no-meat fed controls ( % 54 55 , ), feeding heme increased ATNC levels in feces of mice also fed nitrite ( 56 ). Lewin et al. showed that in human volunteers fecal ATNC concentrations correlate with N-nitroso-specific adducts, O -carboxymethylguanine ( 6 57 ). The dark cooked meat with nitrite, oxidized diet, which contained more [ ] nitrosyl heme than the other diets ( Table 3 ), led to a nine-fold increase in fecal ATNC excretion ( Table 4 Figure 2 , ). Fecal ATNC may not promote ACF formation ( 11 52 , ), but may explain the MDF promotion observed here.

The horse meat market in France 1 IFCE, pôle développement innovation et recherche, 61310 Exmes, France 2 MOISA, INRA, CIHEAM-IAMM, CIRAD, Montpellier Supagro, Univ Montpellier, Montpellier, France 3 MRM - IAE, Montpellier University, pl. E. Bataillon, 34095 Montpellier, France

6 Departamento de Fitotecnia, Escola de Ciˆencias e Tecnologia, Universidade de ´ Evora, P´olo da Mitra, Ap. 94, 7002-554 ´ Evora, Portugal Correspondence should be addressed to Marta Laranjo; mlaranjo@uevora.pt Received 6 November 2017; Accepted 7 November 2017; Published 21 November 2017 Copyright © 2017 Marta Laranjo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

In human, circulating levels of 25-OH-D are largely linked to the consumption of oily fish, margarine and foods containing vitamin D, exposure to sunlight ( Zerwekh, 2008 ), epidermal concentration of 7-dehydrocholesterol, melanin pigmentation, latitude, season, and exposure time of day ( Olmos-Ortiz et al. 2015 ). Exposure of rats to ultra- violet light leads to a 40-fold increase in vitamin D. In con- trast, similar irradiation of dogs and cats does not signifi- cantly increase dermal vitamin D concentration ( How et al. 1994 ). Most herbivores can produce vitamin D in response to ultraviolet irradiation of the skin, as indicated by the higher concentrations of serum vitamin D in shorn sheep compared with unshorn sheep ( Hidiroglou et al. 1985 ). Fur- thermore, when transferred to lower altitudes or higher lati- tudes where solar radiation is much lower, serum vitamin D concentrations in llamas and alpacas decline to low levels, especially during winter ( Van Saun et al. 1996 ). Baby la- mas born in autumn/winter that had lower vitamin D con-

et al. (2011) pointed in addition to effects from information and media coverage, as well as the objective (factual) and subjective (perceived) knowledge of consumers, and the possible role of product labelling. They explicitly referred to the role of media, the content of media reporting and the quantity of media coverage as determinants of consumer acceptance or rejection. An interesting remark is the fact that even positive intended information can fuel consumer resistance because it can increase awareness of previously unknown risks (Verbeke et al. 2007). Driessen and Korthals (2012) mentioned the fact that the development of cultured meat had already given rise to heightened media attention in the Netherlands, for example, and this prior to the highly publicized tasting of the first cultured meat burger in August 2013 in London (Hopkins 2015). Goodwin and Shoulders (2013) analysed the media coverage about cultured meat in the United States (U.S.) and the European Union (prior to the August 2013 cultured burger tasting) and concluded that print media were primarily supporting the idea of cultured meat production. Problems associated with conventional or traditional meat production as well as the advantages of cultured meat were mostly discussed in the print media, and information sources included mainly proponents of cultured meat, which may have positively influenced initial consumer reactions. However, details on the technology described by the print media were felt to be too technical and possibly confusing for the wider public. A more recent analysis of Western media coverage after the August 2013 cultured burger tasting (Hopkins 2015) concluded that mass media provided a quite distorted picture of the obstacles in the path of cultured meat acceptance, notably through portraying mainly vegetarian consumers’ reactions and referring mainly

However, according to some experts, the capacity of meat production by conventional means is close to its maximum (FAO 2011) and further production, even if possible, would come at high costs of greenhouse gas emission, land usage, energy use and water use (Post 2014). Given the appro- priate technology is developed, meat alternatives have the potential for three major advantages over traditional meat production which make them attractive in this climate of increasing demand coupled with diminishing resources. These advantages are: (i) less and less usage of animals (Dawkins and Bonney 2008), even need of almost no an- imals which may solve welfare and moral issues; (ii) less environmental impact of meat alternatives than production of meat from alive livestock (Tuomisto et al. 2011); and (iii) the ability for mass production to take advantage of economies of scale (Post 2012). Among meat alternatives, in vitro meat produced from stem cells is presented as an interesting process because it mimics natural meat, not only in shape and aspect, but also in biological composition because

Abbreviations of diet names: CON-10, control diet; All experimental diets contained 55% processed meat: LCNA, [light cooked meat with nitrite, anaerobic]; DCNA, [dark cooked meat with ni[r]

Omer Abdelhadi 1 , Salih Babiker 2 , Ibtihal Mohamed 3 , J.F. Hocquette 4 , Bernard Faye 5 1 University of Kordofan, Animal Science, Sudan 2 University of Khartoum, Fac. of Animal Production, Sudan 3 Qatar University, Biological and Environmental Science, Qatar 4 INRA, Herbivore Research Unit, France