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Meat and meat products consumption and cancer Dr. Karl O. Honikel Chairman of Nutrition and Health Working Group CLITRAVI Preface During the meeting of the Nutrition and Health Working Group at the annual meeting of CLITRAVI in Toulouse on 13 May 2009 the idea arose to compile and evaluate the most recent data on meat/meat products and cancer. As the chairman I have collected and read in the last few months quite a number of papers and reports. The result is quite promising. Contrary to the decades before when positive papers on meat were only published by meat oriented people, now scientists well recognized as toxicologists, nutritionists or medical doctors report that meat is good for you and should be a part of a balanced diet. I assume that the rather aggressive statements (some call it “nannying” the consumer) of the 2nd World Cancer Research Fund report (WCRF II) published in a joint effort with the American Institute for Cancer Research (AICR) in November 2007 and the way it was made public triggered some recent publications and statements. Even the International Agency for Research on Cancer (IARC) in Lyon which published in the years before (see the paper of Norat et al in the table) and by the E. Riboli a former scientists in the IARC sounds nowadays much more careful. In http://www.iarc.fr IARC states in a report of December 2008: “The high expectations we had that epidemiological studies would discover that the dietary habits are associated with increased or decreased cancer were not realized”. They continue later on: “In particular intakes of fat, fruit, vegetables and of meat either not associated or only slightly associated with colorectal, breast or prostate cancer occurrence”. Other critical remarks on the WCRF II have been published elsewhere. Now the WCRF/AIRC rows backwards in a new report (WCRF 2009), see table for details. Despite this promising outlook we should take this worldwide read and accepted report WCRF II serious and I will evaluate the points on meat in the following. Points to observe in the WCRF reports The report II of the World Cancer Research Fund (WCRF II) was published (see table, paper 5) with 2 parallel press conferences in Washington, DC and London in November 2007. We still have a short statement about it in the CLITRAVI homepage. WCRF published it in a joint venture with the American Institute for Cancer Research (AICR) and it was supported by leading scientists worldwide in its evaluations of about 7000 publications and conclusions on food and cancer and opinions drawn finally by a panel of toxicologists. The studies evaluated on meat and cancer are much smaller with 12 and 5 studies (see table). The opinions have caused in some countries and with several governments the concern that besides other causes the eating of red meat and processed meat may promote colorectal cancer. The WCRF panel states that there is a relationship of colorectal cancer and intake of red meat / processed meat with “Convincing Evidence” This “convincing evidence” is met in the foods area only by alcohol and aflatoxin contaminated foods. However, a BMI >30, no or low physical activity and other none food attributed behaviours like smoking are even worse with convincing evidence for 7 different kinds of cancer. The report received criticism from many sides mainly by opposing its “nannying” recommendations. In a new report of WCRF in 2009 called” The Policy and Action for Cancer Prevention Food, Nutrition and Physical Activity: a Global Perspective” (WCRF 2009), see table for details, they step back slightly and state that is was by no means their intentions to tell the people what to eat. In the Appendix A of this report on page 150 they try on the example of red meat to improve their statements by stating that eating red meat between 10 and 80g/day has a relative risk (RR) of 1.03 and a Population Attributable Fraction (PAF)of cancer incidence of 5% for colorectal cancer calculated for UK. A RR of 1.03 is regarded in such statistical evaluations as not significant at all, (actually up to RR 1.1 values are regarded as insignificant) and a 5% PAF lets one wonder where the “Convincing Evidence” remains. But as it is common this second statement only a few people will read and take up in their judgements. Thus I will take a look at the arguments of the November 2007 report. 1. The panel recommends with regard to meat a.) to eat as an individual <500g cooked red meat including the part of red meat in the processed products per week. This is equivalent to 71g red meat/day. In the report (WCRF II) on several pages and especially in the printed summary of the report it is said that the 500g are calculated from 700 to 750g raw red meat. It means that on processing and preparation one looses 29 to 33% of the raw weight. It is, however, a long experience in the meat business and catering that preparing fresh meat result in a loss of 15 to 25%. Let us take a mean value of 20 %. The apparently intended figure for intake of red meat by the WCRF panel is based on 700 to 750g raw meat. Nutritionists who refer to the WCRF report state indeed 100g raw red meat/ day. This is equivalent to 80 g prepared meat /day. This figure is the value in the new report with 10 to 80g/day (WCRF 2009) and an RR of 1.03. What about the processing? In the 80g/day also the processed red meat is included. Do we loose weight during processing? I calculated it taking into account the cooked and nonheat treated meat products. By adding water, salt and additives to the meat in heated product and the loss of weight in the non-heat treated dried products one ends up at about 97 to 103 g per 100g raw meat, depending on the percentage of the meat product groups which varies between the countries. Thus we can state that there is no weight loss in processed meat in comparison to the raw meat used. In order to avoid too much complexity I recommend that we take 80g/day prepared and processed red meat also used by the WCRF in the new 2009 report as the figure for further calculations keeping in mind that this is a conservative value. According to our calculations in the list of last year for meat and meat products intake and composition (see annex 1 to NUT/08/057) compiled vs the unsatisfying list of EFSA for nutritional profiles and thresholds we stated that the average European consumer has 150g of raw meat available/day of which 2/3 = 100g/day is red meat. Thus we can state that the European consumer eats the amount what the WCRF panel recommends for an individual as the maximum value. We assume further on that of the total meat 40% is processed. That means 40% of 150g is 60g/day are used for processed meat resulting in 48g processed meat products (80%) of which we can assume that 75% are made from red meat which is equal to 36g/day. Taking then the white meat remaining it means that 50g/day are available as raw material resulting in 40g prepared white meat (80% of raw). b.) The panel states that all processed meats should be avoided. In Europe it means according to the calculations above that 36g processed red meat and about 12g of processed white meat, total 48g/day of processed meat, are produced. They should be avoided. 2. Causes for red meat/processed meat and cancer The expressions and explanations of the WCRF II report about the causes for red meat and cancer are not very clear. The panel gives only hints what could be the cause for the convincing evidence which they state. In the text they indicate some possible causes: i.) the nitrite in the food itself forming nitrosamines in the food and the body. In other parts of the report, however, they clearly say that 70 to 90% of the nitrite comes by reduction in the body and saliva from plant nitrate. Furthermore studies since 3 decades show very clearly that meat products themselves contain very low concentrations of nitrite and nitrosamines for various reasons. ii.) free iron as a transition metal can easily take up various states of oxidation. Fe2+, Fe3+ and Fe4+ are common in food. In raw meat without any question the Fe is bound. In cooked meat some iron is free. Also it is a known fact that the iron in meat is absorbed in the intestines about 4 times higher than plant iron (ca. 20 vs 5%). Absorbance means it must have been at least free iron for some time to be absorbed. By the change of oxidation status Fe ions promote radical formation. Myoglobin with its iron containing porphyrin moiety is believed to be involved in the radical forming process. The presence or addition of antioxidants like ascorbate will prevent the formation of radicals. This indication by the panel cannot be put aside. It is the most serious one. We should consider doing something about it. iii.) Heterocyclic aromatic amines (HAA) or polycyclic aromatics hydrocarbons (PAH) are definitely no serious problem in products. The HAA and PAH may occur in frying and grilling of meat and to a lower extent in meat products. Actually much more HAA precursors are present in the white poultry meat which is supposed to be less “dangerous”. Heavy metals are very low in European meat cuts and products. PCB, Dioxins and related compounds are present in meat but in much smaller amounts than in dairy products which show no such incidence of cancer. iv.) The panel also mentions the fatty acid composition of meat and cholesterol as a cause for cancer. It is more than astonishing actually irritating that these people who dare to make recommendations about cancer evidence do not know the basic facts of textbooks on nutrition that meat and meat fat is not rich in saturated fatty acids and cholesterol. In their ignorance they point to the statements of saturated fatty acids in dairy products in which indeed the saturated fatty acids are higher with about 65%. 3. The panel recognizes also that in the studies used for evaluation the definitions of meat and meat products vary considerably. I myself read through several of the original papers. In some the expression of meat is defined as all meat in cuts including cooked and raw ham but interestingly in one paper not bacon. They define as meat products every processed meat which is minced or comminuted including even minced meat itself which has in Hamburgers quite a share of 5-10%. Others call processed meat everything with a cured red colour. Taking such a variation into account how can the conclusions be compared? Nevertheless the panel does so. Sometimes in white meat also fish is included. 4. Red meat is defined meat from bovines, porcines, goat, sheep, and wild animals. White meat is then in consequence the meat of all birds. Even accepting that ducks and geese together with wild birds are of minor importance, the fact that some turkey muscle contain at least the same or more myoglobin then some porcine muscles has not been taken into account. Chicken and turkey carcasses do not contain light breast muscles only. 5. Statistical approach in the studies evaluated. In nearly all of the studies used by the WCRF for the evaluation of meat and cancer incidents meat is the only food, sometimes also fish, at which the authors look. Besides food the age, gender, race, physical activity, BMI and smoking are evaluated for cancer. That means that other foods are neglected and not statistically evaluated which is even often stated in the introduction of the papers. It is also a common approach and applied also in the WCRF report that the highest vs the lowest intake is compared and the high RR is taken for evaluation and reported. As an example the most recent paper of Sinha et al. (see table for details) compares the eating of about 200g red meat/day with the low intake of 97g/day and states the high RR as the relevant figure for the cancer incidence. The RR for the 97g/day is set at 1.00. Furthermore very interesting in this paper is the fact that the amount of meat and products and of what species and cut (fat/energy content) eaten in the last 12 months was asked retrospective twice in 10 years of follow-up. Everybody can do the testing himself: what did you eat in September 2008 as meat, products, which cut which species and what other foods did you eat and in which quantity? Sinha et al. came to the statistical conclusion that the RR of highest 200g/day vs. lowest 97g/day was 1.44. Using the Sinha figures in its quintiles and applying it to European conditions, then the RR is 1.07. This is as said above of no statistical significance. Conclusions Reading the reported facts and figures and investigating in detail the figures I wonder how the panel comes to such conclusions. But due to the importance and worldwide acceptance of the WCRF which is a joint venture with the powerful AICR we must take their statements seriously and we should investigate the questions involved. Demeyer, De Smet and I have made last year in the Meat Science paper some recommendations for research. Little reaction has been reported to me. In the list below I compiled some publications of recent years which are often cited or used pro and contra meat and meat products. Even if the opinions are no longer unisono against meat we should be aware that it will take a full generation or its professional period to change the opinions. Finally I recommend reading the cited paper of Jarvis 2007 for arguments. References 1. Sandhu M.S.and White I.R.(2001). “Systematic review of the prospective cohort studies on meat consumption and colorectal cancer risk: a meta-analytical approach”. Cancer Epidemiol Biomarkers Prev 10: 439-446 2. Norat, T., Lukanova, A., Ferrari, P., Riboli, E. et al. (2002). “Meat consumption and colorectal cancer risk: dose-response meta-analysis of epidemiological studies”. International Journal of Cancer 98: 241-256 3. Chang-Claude, J., Hermann, S., Eilber, U., and Steindorf, K. (2005), Life-style Determinants and Mortality in German Vegetarians and Health-conscious Persons. Results of a 21 Year Follow-up, Cancer, Epidemiol. Biomarkers Prev.14(4) 963-968 4. Larsson, S.C., Wolk, A., (2006). “Meat consumption and risk of colorectal cancer: A meta-analysis of prospective studies”. International Journal of Cancer, 119: 2657-2664 5. The World Cancer Research Fund/American Institute for Cancer Research (2007). “Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspectiv”. Washington, DC, AICR, 6. Policy and Action for Cancer Prevention, Food, Nutrition and Physical Activity: a Global Perspective WCRF and AICR, Washington , DC (2009) 7. Sinha, R., Cross, A., Graubard, B.I., Leitzmann, M.F, Schatzkin, A., (2009). “Meat Intake and Mortality“, Arch. Intern. Med, 169, 6, 562-571 8. Key, T., J., Appleby, P., N., Spencer, E., A., Travis, R., C., Roddam, A., W., Allen, N., E., (2009), Cancer Incidence in Vegetarians: Results from a European Prospective Investigation into Cancer and Nutrition (Epic –Oxford) Am. J. Clin. Nutr. 89, supplement 1S-7S 9. Alexander, D., D., Cushing, C. A., Lowe, K.A., Sceurman, B., and Roberts, M.A. (2009) Metaanalysis of Animal Fat and Animal Protein Intake and Colorectal Cancer, Am. J. Clin. Nutr. 89, 1-8 Other reports either general or on specific cancer types: EPIC-Studie 2009. http://epic.iarc.fr/ [online 8. Juni 2009] Gonzalez et al. (2006). “Meat Intake and Risk of Stomach and Esophageal Adenocarcinoma within the European Prospective Investigation Into Cancer and Nutrition (EPIC)”; Journal of the National Cancer Institute, Vol. 98, No. 5, March 1, 345-354 MF Faramawi, E Johnson, MW Fry, M Sall and Z Yi (2006). “Consumption of different types of meat and the risk of renal cancer: meta-analysis of case-control studies.” Cancer Causes and Control 18: 125-133 Jarvis, W.T., (2007), The Role of Meat in the Diet, Misinformation and Misbelief, Proc. 60th Reciprocal Meat Conference, Brookings S:D. AMSA Chicago Ill. USA 1-11 Table: Meta-analyses and publications on red meat and cancer year type of analysis area 2001 13 prospect. studies USA, NL, JP,SF 2002 9 prospect. studies worldwide 1973-99 2005 1 prosp.study D veget. 2006 15 prosp. st. on red meat (N=7400 p) 14prosp.st. meat products (N=7900) 2007 12 prosp.studies. red meat 5 prosp.studies proc. meat worldwide 2009 addition to WCRF 2007report 2009 1 prosp. study 2009 1 prosp.study 2009 6 prosp. study worldwide 1975-2005 USA UK, EPIC Oxford worldwide animal fat animal protein cancer type result and rel.risk (RR) colorectal 100g/d totalmeat 1.15 25g/d products 1.49 colorectal low vs high red meat 1.35 proc.meat 1.31 cancer veget vs meateater meteater -17% colorectal low vs high red meat 1.28 meatproducts 1.20 colorectal >100g rawmeat/d 1.43 >50g proc.meat 1.21 reference 1 2 3 4 5 WCRF colorectal red meat 1080g/d 1.07 6 WCRF page 150 cancer 7 low vs. high high ca.200g/d 1.44 colorectal nonveget. vs.veget. 0.84 colorectal low vs. high 1.02-1.04 1.05 8 9