Dietary exposure to meat-related carcinogenic ...

http://informahealthcare.com/ijf ISSN: 0963-7486 (print), 1465-3478 (electronic) Int J Food Sci Nutr, Early Online: 1–7 ! 2014 Informa UK Ltd. DOI: 10.3109/09637486.2014.917146

COMPREHENSIVE REVIEW

Dietary exposure to meat-related carcinogenic substances: is there a way to estimate the risk? Joanna Trafialek and Wojciech Kolanowski

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The Faculty of Human Nutrition and Consumer Sciences, Warsaw University of Life Sciences, Warsaw, Poland

Abstract

Keywords

N-Nitroso compounds (NOCs), heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PHAs) are examples of carcinogenic substances, which are formed during cooking and processing of meat. Many researches suggest that high consumption of meat is positively associated with increased risk of some cancers. The majority of the researches are of epidemiological nature and, therefore, provide only associations related to population exposure to diet-related carcinogenic substances. The individual’s exposure risk may be estimated by using food frequency questionnaire and analytical methods. However, there is a lack of methods which enable estimation of the risk concerning particular meat meals. The purpose of this paper was to summarize and emphasize the importance of factors influencing the formation of carcinogenic substances in meat during cooking.

Carcinogens, cooking methods, heterocyclic amines, meat, polycyclic aromatic hydrocarbon

Introduction Dietary carcinogens constitute one of the major causes of carcinogenesis in humans (Sugimura, 2000). Mycotoxins, pesticide residues, dioxins, N-nitroso compounds (NOCs), and oxidative agents are some examples of carcinogenic substances related to food. Some carcinogens are formed during cooking in high temperature, e.g. acrylamide, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs) (Ferguson, 2010; Parzefall, 2008). Cooked meat is one of the major dietary sources of NOCs, HCAs, and PAHs (Keszei et al., 2013). A growing body of research suggests that consumption of cooked meat is linked to cancer (Cross et al., 2007). To enhance individual’s, as well as the whole population, health, there is a need to diminish exposure to carcinogens also from the diet. The most important strategy to decrease the risk of some types of cancer is to increase consumer’s awareness and knowledge on diet-related hazardous factors. The next step could be to use calculation methods thanks to which it would be possible to estimate the risk of carcinogenic substances in the diet, especially in cooked meat meals, both by the individual consumer and by diet advisors. There are many factors affecting carcinogens formation during cooking. Thus, the purpose of this paper was to summarize and emphasize the importance of factors influencing the formation of carcinogenic substances in meat during cooking.

Meat in the diet Meat can be divided into red meat (beef, pork, mutton/lamb, horse, and goat), processed meat (all meat products, including ham, bacon, sausages, hot dogs, salami, etc.), white meat (poultry, Correspondence: Wojciech Kolanowski, The Faculty of Human Nutrition and Consumer Sciences, Warsaw University of Life Sciences, Nowoursynowska str. 166, 02-787 Warsaw, Poland. Tel: +48 22 5937079. Fax: +48 22 5937058. E-mail: [email protected]

History Received 10 August 2013 Revised 1 April 2014 Accepted 8 April 2014 Published online 14 May 2014

including chicken, hen, turkey, duck, goose, unclassified poultry, and domestic rabbit), and fish. High consumption of meat, especially red, is common in many societies (Daniel et al., 2011). In developed Western countries, average meat consumption is ca. 100 kg per person per year, i.e. ca. 270 g/d. In contrast, average meat consumption in developing countries reaches ca. 30 kg per person per year, i.e. ca. 80 g/d (Food and Agriculture Organization, 2009). However, depending on the preferences and capacity, one consumer may eat more than 200 kg per year and others – much less amounts or nothing at all, e.g. vegetarians. Meat in the diet is an important source of essential nutrients like protein, iron, zinc, B-vitamins B, A, and fat. The bioavailability of iron and folate from meat is much higher than from plant foods such as grains and vegetables. However, the nutritional weakness of meat, particularly red one, is the high content of cholesterol and saturated fatty acids, as well as homocysteine, which is formed during meat protein metabolism. These compounds were shown to be positively associated with plasma low-density lipoprotein (LDL) concentrations and the risk of cardiovascular diseases (McAfee et al., 2010; Mozaffarian et al., 2010; Pan et al., 2012). Meat is also a natural dietary source of L-carnitine. However, recently Koeth et al. (2013) showed that L-carnitine (both from meat and from supplements) can be easily converted by gut bacteria into the compound trimethylamine N-oxide (TMAO) an emerging risk factor for arteriosclerosis. The authors pointed that L-carnitine, rather than saturated fat and cholesterol, explain the link between red meat consumption and cardiovascular diseases. Moreover, meat is the best source of iron in the diet. Although iron is essential for the prevention of anemia, too high intake of heme iron is related to the endogenous formation of NOCs in the gastro-intestinal tract which may promote cancer (Bingham et al., 2002; Joosen et al., 2009). Thus, in excess heme iron may be, above others, the risk factor for some types of cancer, e.g. colorectal cancer. Colorectal cancer is the third most common


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type of cancer in humans (Hebels et al., 2011; Kim et al., 2013). Nevertheless, in meat several potential anticarcinogens can be found including omega-3 polyunsaturated fatty acids (especially in fish) or conjugated linoleic acid (present in ruminant meats, e.g. beef, lamb) (Ferguson, 2010). Red meat in particular is also an important source of micronutrients with anticancer properties including selenium and B-vitamins (Ferguson, 2010). Meat and meat-based products are almost always cooked before being eaten. The cooking process not only destroys pathogenic or spoilage microorganisms and increases digestibility of proteins but also develops food taste, color, flavor, and texture, which are characteristic to cooked meat. Despite nutritional value and highly acceptable flavor, cooked meat may be also a source of carcinogenic substances usually related to meat processing and cooking (Kim et al., 2013; McAfee et al., 2010). Red meat contains high amount of heme iron, as well as amino acids, carnitine and creatine, which are the main source of HCAs formation during cooking (Turesky, 2007). Moreover, many consumers prefer well-done strongly heated meat and meat products, which were charcoal-grilled/barbecued, pan fried or roasted, prepared at home, outdoor, or in restaurants (McKenna et al., 2004). Such food is characterized by high palatability and dark, flavorful crust formed during cooking (Reicks et al., 2011; Shrestha et al., 2010). However, most consumers do not realize the risk of such cooking process, which can result in elevated formation of substances dangerous to human health by decreasing food safety (Danowska-Oziewicz, 2009; Lu¨cke & Trafialek, 2010). Food quality and safety are of paramount concern to modern consumer. However, even health-conscious consumers find it hard to maintain a healthy diet, particularly with regard to cancer risk. Carcinogenic substances were found in a wide variety of cooked or processed foods, especially meat and fish (Kikugawa, 2004; Sugimura et al., 2004). Substances found in cooked meat, which fall into the category of dietary carcinogens are NOCs, HACs and PHAs. N-nitroso compounds NOCs are known to be the risk factor for colon cancer (Hebels et al., 2011). Nitrosamines are NOCs of the highest carcinogenic activity. Ingestion of nitrates and nitrites can cause endogenous formation of NOCs in human gut. Red meat is considered the most important dietary component linked to NOCs formation, although nitrates and vitamin C also contribute (Holtrop et al., 2012). Vitamin C was shown to counteract NOCs formation in vitro and in humans (Holtrop et al., 2012). Nitrates are components of curing salts and can be found in processed meat and pickled fish. Nitrates help kill bacteria, produce a characteristic flavor, and preserve pink or red color of meat products. Nitrates are also used as fertilizers in agriculture and may be found in vegetables and fertilizer-contaminated water (Bruning-Fann & Kaneene, 1993). Oxidation of nitrates to nitrites may be caused by the action of nitrifying bacteria delivering free nitrites into the gastrointestinal tract for acid catalyzed N-nitrosation (Kuhnle et al., 2007; Loh et al., 2011). NOCs are products of reaction of nitrites with amines, some of them are carcinogenic and others might be easily converted into carcinogens. For example, nitrosoproline (Figure 1) can be decarboxylated to nitrosoprrrolidyne during heating of cured meat (Lijinsky, 1992). Additionally high intake of heme iron with meat increases the endogenous formation of NOCs (Cross et al., 2003). Iron can cause oxidative stress and DNA damage and heme iron can catalyze the formation of NOCs, as well as cytotoxic and genotoxic aldehydes by peroxidation of lipids (Bastide et al., 2011; Bingham et al., 2002). It was shown that NOCs may

Int J Food Sci Nutr, Early Online: 1–7

Figure 1. Formation nitrosoproline.

of

carcinogenic

nitrosopyrrolidine

form

Figure 2. Formation of carcinogenic MeIQ from creatine.

promote gastric, bladder and oesophagal cancers (Ferrucci et al., 2010; Keszei et al., 2013). HCAs HCAs are a group of procancerogenic substances identified in meat cooked to the well-done stage, in pan residues and in meat surface that shows a crispy brown crust (Kinze et al., 1999). More than 20 HCAs were identified in cooked meat among which the most carcinogenic is MeIQ (2-amino-3,4-dimethylimidazo(4,5-fquinoline) (Skog et al., 1998; Sugimura, 2000). HCAs undergo metabolic activation by N-hydroxylation of the exocyclic amine groups to produce intermediate arylnitrenium ion which is the critical metabolite implicated in toxicity and DNA damage (Turesky & Le Marchand, 2011). HCAs are formed in high-protein foods during heat treatment in temperatures over 160 C. The higher the temperature of meat treatment is, the more the HCAs are formed (Skog & Sloyakov, 2002). Precursors of HCAs are free amino acids found in muscle tissue mainly creatine and creatinine. HCAs are formed as a result of Maillard reactions in conditions typically applied for meat cooking (Kikugawa, 2004). HCAs are formed when creatine, other amino acids, and glucose are heated together at high temperatures range from 125 to 300 C or cooked for long periods of time (Figure 2). HCAs form at lower end of this range when the cooking time is long, at the higher end of the range HCAs are formed within minutes (Skog et al., 1998). The less creatine and creatinine content in meat, the fewer HCAs are formed (Kikugawa, 2004). Environmental acidity (pH) also plays an important role during Maillard reactions. Hence, the formation of HCAs depends also on meat pH (Ja¨gerstad et al., 1998; Skog & Sloyakov, 2002; Turesky, 2007). The highest HCAs level was determined in juice exuded from meat during cooking (roasting, grilling) (Kinze et al., 1999). The juice is rich in free amino acids and contact with high temperature of cooking, which increases HCAs formation. Due to rich, highly acceptable flavor, the heated meat juice together with meat fat, which also exudes from meat during cooking, are components of gravy commonly used as dressing for meat meals. HCAs produce strong carcinogenic and mutagenic action (Zheng & Lee, 2009). Total HCAs concentrations in cooked meat generally range from less than 1 to about 500 mg/kg but usually are less than 100 mg/kg (Kinze et al., 1999; Salmon et al., 2000). Laboratory grilled samples were reported to contain much high HCAs levels over 300 mg/kg (Kinze et al., 1999). The effects of cooking methods on the formation of HCAs in poultry meat were

DOI: 10.3109/09637486.2014.917146

investigated by Liao et al. (2010). In the case of chicken breast, the highest HCAs level was found in charcoal-grilled meat 34.6 mg/kg, in pan fried 22.5 mg/kg, and in deep fried only 3.2 mg/kg (Liao et al., 2010). HCAs intake may contribute to the development of cancer by causing mutations in genes, causing new cells to grow in an uncontrolled manner, and form a tumor (Kim et al., 2013). Epidemiological studies have linked consumption of well-done meat with an increased risk of colon and rectum cancers (Kim et al., 2013; Weisburger, 2002). Rohrmann et al. (2009) found that the relative risk for colorectal cancer was increased at HCAs intakes at level over 41.4 ng/d.


PAHs PAHs are formed by the incomplete combustion of organic matter. PAHs are present in the atmosphere, water, sediments, tobacco smoke, and foods (Codex Alimentarius Commission, 2005). In foods, PAHs are generated during meat smoking and grilling (Alomirah et al., 2011). About 660 different compounds belong to the PAHs group, seven of which show carcinogenic, mutagenic, and teratogenic properties (Phillips, 1999). The most well-known carcinogenic PAHs is benzo(a)pyrene (Figure 3) (Stolyhwo & Sikorski, 2005). As a direct consequence of smoking, phenolic substances are generated. They are important for the sensory properties of smoked meat products and also prevent unsaturated fatty acids against oxidation. In some countries, a lot of smoked meat is consumed, e.g. in Germany about 60% of meat products are smoked (Hitzel et al., 2013). Exposures to PAHs should be as low as reasonably achievable (Codex Alimentarius Commistion, 2005). Processing of food (such as drying and smoking) and cooking of meat at high temperatures (grilling, roasting, and pan frying) are major sources generating PAHs (Phillips, 1999). Extremely high benzo(a)pyrene content at the level of 700 mg/kg was found in sausage smoked at uncontrolled domestic conditions (Dobrikova & Svetlikowa, 2007). In developing countries, smoking is carried out in traditional way at very high temperature. Study of Essumang et al. (2012) showed that in Ghana the mean total PAHs level in smoked sardines ranged from 510 mg/kg to 1460 mg/kg. Laboratory fried hamburgers contained PAHs at level up to 38 mg/kg (Kinze et al., 1999). Levels as 200 mg/kg were found in smoked fish and meat. In charcoal-grilled meat, the level of 130 mg/kg was reported, whereas the average background PAHs values are usually in the range of 0.01–1 mg/kg in uncooked foods (Codex Alimentarius Commission, 2005). Charcoal grilling is an intense thermal process, which results in very high PAHs formation in meat (Alomirah et al., 2011). PAHs levels assessment in duck breast steaks undergoing various cooking treatments for 0.5–1.5 h, showed that charcoal-grilled samples without skin contained the highest amount of total PAHs 320 mg/kg, followed by charcoal grilled with skin 300 mg/kg, smoked 210 mg/kg, roasted 130 mg/kg, and steamed 8.6 mg/kg (Codex Alimentarius Commission, 2005). There are several mechanisms of PAHs formation such as melted fat that undergoes pyrolysis when dripping onto the heat source and pyrolysis of the meat due to the very high temperature contact. However, if dripping of melted fat onto the heat source

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is prevented less PAHs will be formed in the grilled meat (Farhadian et al., 2012). Understanding the conditions that form PAHs can lead to use cooking procedures greatly reducing PAHs level in meat.

Meat consumption and cancer Much of the global variation in cancer incidence was attributed to environmental influence including dietary preferences (Giovannucci et al., 1994; Larsson & Wolk, 2006). High consumption of meat, particularly red, processed and strongly heated may be related to increased risk of some types of cancer, e.g. colorectal, pancreatic, bladder, breast, and prostate cancers (Anderson et al., 2012; Cross et al., 2007; Koushik et al., 2007; Parr et al., 2013). Meat could be involved in carcinogenesis via multiple carcinogenic compounds related to cooking and processing (Ferrucci et al., 2010). Several epidemiological studies, meta-analyses, and clinical studies showed that high intake of meat, particularly red and processed meat, were positively associated with increased cancer risk, especially colon cancer risk (Alexander et al., 2011; Cross et al., 2007; Giovannucci et al., 1994; Kim et al., 2013; Larsson & Wolk, 2006; McAfee et al., 2010; Sandhu et al., 2001). However, some authors did not confirm such association (Loh et al., 2011; Par et al., 2013; Truswell, 2002). Nevertheless, World Cancer Research Fund and American Institute for Cancer Research (WCRF) report based on an extensive review of the existing evidence concluded that research supporting the association between red and processed meat intake and colon cancer risk was convincing. The risk of colon cancer was estimated to increase by 29% for every 100 g/d increase in red meat consumption and by 21% for every 50 g/d increase in processed meat consumption (World Cancer Research Fund/American Institute for Cancer Research, 2007). Moreover, meat cooking methods and doneness level additionally increase the risk of colorectal and other cancers (McKenna et al., 2004; Sinha et al., 1999). High level of salt usually used in grilled or processed meat may also increase the risk of gastric cancer (Kelley & Duggan, 2003). In addition to colorectal or gastric cancer risk, some epidemiological studies reported positive correlation between intake of meat cooked in high temperature and pancreatic and bladder cancer (Anderson et al., 2012; Ferrucci et al., 2010). Moreover, it was suggested that high red meat intake in adolescence may increase the risk of premenopausal breast cancer (Koushik et al., 2007; Linos et al., 2008). The Iowa Women’s Health Study results showed also a dose–response relationship between doneness levels of consumed meat and breast cancer risk. The adjusted odds ratios for very well-done meat versus rare or medium-done meat were 1.54 for hamburger, 2.21 for beef steak, and 1.64 for bacon. Women who consumed these three meats frequently very well-done had a 4.62 times higher risk than that of women who consumed the meat rare or medium-done (Zheng et al., 1998). The risk of breast cancer was also elevated with increasing intake of well-done to very welldone meat. Thus consumption of well-done meat that increases exposure to HCAs and other compounds formed during high temperature cooking may play an important role in the risk of breast cancer (Steck et al., 2007).

Hazard factors of carcinogens presence in cooked meat

Figure 3. Formation of benzo(a)pyrene from simpler hydrocarbons during incomplete combustion of organic matter.

There are many hazard factors that influence the carcinogenic substances occurrence in cooked meat. Some of them may be estimated by every health-conscious consumer, which could be helpful in decreasing the exposure to cooked meat-related carcinogens.


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Red meats are usually cooked at higher temperature and for longer time than more delicate white meats and fish, which results in usually higher HCAs concentration in red meat meals (Trafialek & Przybylski, 2011). Additionally, due to higher level of heme iron the risk of N-NOCs formation in red meat is higher, especially when the meat is processed and cooked (e.g. hamburgers, sausages). So meat type influences the potential level of health-hazardous substances formation during cooking (Anderson et al., 2012). High temperature of cooking is positively associated with level of carcinogenic substances in meat. It was shown that temperature increase by 40 C (from 160 C to 200 C) as well as lengthening the cooking time can cause even four-fold increase in HCAs content (Skog et al., 1998). The most hazardous is cooking meat in direct contact with open flame, e.g. traditional charcoal-grilling or roasting. In many Western societies, charcoal-grilling is often chosen by consumers for outdoor cooking, which may contribute to higher risk of dietary exposure to HCAs and PHAs. However, in many developing countries, meat cooking in contact with open flame is common cooking technique. Thus, dietary habits and preferences also influence the exposure risk to meat-related carcinogenic substances. Cooking methods using high or very high temperatures like grilling/barbecuing, pan frying, broiling, and traditional roasting increase HCAs formation. When cooking meat is in direct contact with open flame, the cooking temperature is very high and fat burning results in PHAs formation which penetrate the meat with smoke. Cooking techniques like boiling, oven roasting in bags, as well as deep-frying or microwaving cause the formation of small amount of HCAs and PHAs (Skog & Solyakov, 2002). Long-time grilling, broiling, or pan frying of meat portion on one side, without frequent turning over, contributes to longer contact of meat with the heat source. This increases HCAs content in the more browned outer part. It was demonstrated that frequent turning over of meat during frying process can be an important factor lowering HCAs level (Tran et al., 2002). Salmon et al. (2000) showed that when meat was turned over just once at 5 min, there was a great effect of pan temperature in increasing HCAs formation. However, if the meat was turned every minute during cooking much less HCAs were detected. Thus, cooking at external temperature 160–180 C and turning the meat over every minute greatly reduce the formation of HCAs during meat frying. Usually dark flavorful crust is formed when cooking at high temperature. The higher the temperature, the darker, crispier, and more flavorful is the crust, until it starts to burn. Color and flavor of the crust is an effect of Maillard reactions of free amino acids with sugars which also result in HCAs formation. The darker is the crust, the higher is the HCAs level in meat. Consumption of well-done or very well-done meat may increase cancer risk due to high HCAs formation during cooking in high temperature. Meat doneness level depends on the cooking temperature and time. Very well-done outer meat surface contains 20–300 times higher HCAs level than microwave cooked meat. This is why it is recommended to remove the burnt fragments of meat before eating (Zimmerli et al., 2001). Dietary exposure risk to harmful compounds influences also the serving size of cooked meat. The highest serving size, the longer time of cooking is needed. Long time of cooking in high temperature results in elevated risk of carcinogenic substances formation. Unprocessed meat serving sizes is ca. 85 g which correspond to the size of a deck of playing cards or bar of soap. Processed red meat serving size is usually lower, e.g. bacon – 2 slices (13 g), hot dogs – one (45 g) (Pan et al., 2012). Mean meat serving size (including processed meat products) could be estimated as 50–75 g.


Total meat consumption level may additionally influence the risk. It was established that the higher meat consumption, the higher exposure risk to meat-related carcinogenic substances (Cross et al., 2007; McAfee et al., 2010). Regarding the association between meat intake and cancer the World Cancer Research Fund and American Institute for Cancer Research (2007) advices to consume less than 500 g of red meat per week, i.e. less than 71 g/d, minimize intake of processed meat and avoid cooking meat at very high temperatures. Despite recommendations of health authorities in many countries, the average meat consumption level is much higher. High meat consumption level, especially when cooked at high temperature, may significantly elevate dietary exposure to meatrelated carcinogenic substances. Furthermore, some consumers eat much more meat than average level, which may additionally elevate the risk. Many consumers enjoy consuming meat with gravy. Gravy consists of meat juice and fat run naturally from meat during cooking. Meat juice contains large amounts of free amino acids, which are easily transformed to HCAs in high temperature of cooking. High temperature increases darkness of meat juice and HCAs concentration. However, it is suggested that spices used for meat seasoning can effectively reduce HCAs formation. The most effective were shown to be rosemary, sage, and garlic (Murkovic et al., 1998). Onion addition to minced meat, e.g. hamburger, was found to be a beneficial way to reduce mutagenicity. Antioxidant substances present in spices and virgin olive oil, e.g. phenolic compounds, reduce formation of HCAs during cooking (Kikugawa, 2004). Also marinating of meat before cooking with sour (containing vinegar), oily marinades containing virgin olive oil, lemon juice, and natural spices like onion, garlic, rosemary was shown to reduce the formation of HCAs and PAHs during cooking (Farhadian et al., 2012; Gibis, 2007). Nevertheless, some authors suggest that flavor enhancers like monosodium glutamate (MSG), which often occurs in commercially available meat seasoning blends, may increase HCAs level during meat cooking in high temperature (Tai et al., 2001). Vegetables and fruits consumption together with meat meal may diminish the dietary exposure to meat-related carcinogenic substances due to fiber, vitamin C, and natural antioxidants content. An inverse association between fruit and vegetables and colon cancer risk was observed among individuals with elevated intakes of red and processed meat (Koushik et al., 2007; van Duijnhoven et al., 2009). Fiber, in the form of vegetables, bran, or resistant starch, does not reduce the level of N-nitroso substances, HCAs and PHAs, although carcinogens contact time to intestinal mucosa is diminished by acceleration of peristalsis (Bingham et al., 2002). Most of the fruits and some vegetables are rich in vitamin C, which was shown to decrease HCAs formation (Holtrop et al., 2012). Also flavones and flavonoids, which are found in many fruits, vegetables, cereals herbs and spices, were reported as inhibitors of the HCA-type mutagens (Lee et al., 1992). Other risk factors of meat-related carcinogenic substances formation during cooking like creatine and creatinine content, glucose content, and meat pH cannot be estimated by the consumer.

Estimation of dietary exposure to meat-related carcinogens Many epidemiologic studies showed that diet containing high level of meat and high caloric intake may increase some cancers risk (Cross et al., 2007; Kim et al., 2013). Exposure to carcinogenic substances present in the diet depends on both the food consumption patterns and the concentration of the particular


DOI: 10.3109/09637486.2014.917146

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Table 1. Hazard factors and risk level of carcinogenic substances occurrence in cooked meat. Hazard factor Meat type Cooking external temperature

Cooking method Turning over during cookingb Dark, flavorful crust formation


Meat doneness Seasonings and marinating of meat Gravy consumption (meat juice) Serving size (g) Vegetables and fruits intake with meat

Hazard factor variants a

Processed meat Red meat (raw) White meat (raw) Very high temp. (4200 C) High temp. (160–190 C) Medium temp. (130–155 C) Low temp. (100–125 C) Grilling/barbecuing, pan frying, broiling, traditional roasting Roasting in bags Boiling, stewing or microwaving Often – every minute Rarely Partly burnt surface Brown and crispy crust Light brown and soft crust Pale and soft crust Well done Medium done Rare done Natural spices or acid oily marinates Only salt or none Yes No Large – 150–200 Small – 50–100 Yes No

Expected risk increase High Low Very low Very high High Low Very low or High Moderate Very low or Low Moderate Very high High Moderate Low High Moderate Low Very low or Low Moderate Very low or Moderate Low Very low Low

none none

none none

a

Meat and meat products red and white, cured with nitrate (bacon and sausages) usually cooked or/and smoked. Meat grilled/barbecued, pan fried, or traditionally roasted.

b

substances in food. Exposure to carcinogens present in food may be evaluated by food consumption data collected using food frequency questionnaire method and analytical methods based on chromatography (Alomirah et al., 2011; Bogen & Keanting, 2001; Jahurul et al., 2010). Questionnaire method indicates how often specific food are consumed. Collected data are elaborated by dietitians who, based on the known carcinogenic potency of some substances occurred in food, can formulate recommendations related to the individual’s or the whole population diet. However, there is a lack of methods which could be easy to use by individual health-conscious consumer enabling fast and easy dietrelated health hazards assessment. To estimate probable risk of meat-related carcinogenic substances intake with meat meals, the most important hazard factors should be taken under consideration. Particular hazard factors of carcinogenic substances occurrence in cooked meat are meat type, cooking temperature (external), cooking method, turning over during cooking, dark, flavorful crust formation, meat doneness, seasonings and marinating, gravy consumption, serving size, vegetables, and fruits intake with meat (Table 1). Hazard factors, depending on the variant and intensity, may affect the formation of harmful substances in meat during cooking in varying degree. Thus, possible risk increase of carcinogenic substances occurrence in cooked meat may be estimated from very low (or none), e.g. boiling of meat, to very high, e.g. charcoal-grilling. As presented in Table 1, hazard factors and risk levels of carcinogenic compounds occurrence in cooked meat should be assessed with regard to particular meat meal. Many factors differently influence the risk of carcinogenic substances occurrence in particular meat meal. To estimate the risk special calculation, formula could be developed. Such formula should take into account all hazard factors. This may enable calculation of the average exposure to meat-related carcinogenic substances and the risk estimation.

Conclusions The risk of exposure to meat-related carcinogenic substances varies greatly among individual consumers. It depends on dietary habits and preferences, as well as cooking methods. Raw meat usually contains very low amounts of NOCs, HCAs, or PAHs, which increase during processing and cooking. Consumption of meals prepared from not processed meat may decrease the risk of exposure to NOCs. Reducing the cooking temperature and time seems to be the most effective way to decrease the formation of HCAs, avoiding the conditions where the temperature is below the one needed to kill harmful microorganisms. The formation of PAHs can be reduced by avoiding direct meat contact with heat source and avoiding meat smoking, especially during grilling. Marinating of meat with marinades containing vinegar and natural spices can reduce the formation of HCAs and PAHs during cooking. Moreover, avoiding consumption of gravy (meat juice) and consumption of vegetable and fruit together with meat meal, as well as lowering the total meat consumption level to those advised by health authorities, may diminish dietary exposure to meat-related carcinogenic substances. Future research is needed to elaborate calculation method estimating dietary exposure risk to carcinogenic substances related to particular meat meals. The method may be based on mathematical formula including the most important hazard factors. Such formula may be helpful for health-conscious consumers, as well as for diet advisors and quality control personnel within restaurants and catering companies, to reduce formation of meat-related carcinogenic substances, thus decreasing the risk of some kinds of cancer.

Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

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References Alexander D, Weed D, Cushing C, Lowe K. 2011. Metaanalysis of prospective studies of red meat consumption and colorectal cancer. Eur J Cancer Prev 20:293–307. Alomirah H, Al-Zenki S, Al-Hooti S, Zaghloul S, Sawaya W, Nisar A, Kurunthachalam K. 2011. Concentrations and dietary exposure to polycyclic aromatic hydrocarbons (PAHs) from grilled and smoked foods. Food Control 22:2028–2035. Anderson K, Mongin S, Sinha R, Stolzenberg-Solomon R, Gross M, Ziegler R, Mabie J, et al. 2012. Pancreatic cancer risk: associations with meat-derived carcinogen intake in the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO) cohort. Mol Carcinog 51: 128–137. Bastide N, Pierre F, Corpet P. 2011. Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved. Cancer Prev Res 4:177–184. Bingham S, Hughes R, Cross A. 2002. Effect of white versus red meat on endogenous N-nitrosation in the human colon and further evidence of a dose response. J Nutr 132:S3522–S3525. Bogen K, Keating G. 2001. U.S. dietary exposures to heterocyclic amines. J Exp Anal Environ Epid 11:155–168. Bruning-Fann C, Kaneene J. 1993. The effects of nitrate, nitrite and N-nitroso compounds on human health: a review. Vet Hum Toxicol 35: 521–538. Codex Alimentarius Commission. 2005. Joint FAO/WHO Food Standards Programme. (2005). Codex Committee on food additives and contaminants. Discussion paper on polycylic aromatic hydrocarbons (PAH) contamination CX/FAC 05/37/34. Hague, the Netherlands: FAO/WHO. [Online] Available at: ftp://ftp.fao.org/codex/meetings/CCFAC/ CCFAC37/FA37_34e.pdf. Accessed on 27 December 2013. Cross A, Leitzmann M, Gail M, Hollenbeck A, Schatzkin A, Sinha R. 2007. A prospective study of red and processed meat intake in relation to cancer risk. PLoS Med 4:e325. Cross A, Pollock J, Bingham S. 2003. Haem, not protein or inorganic iron, is responsible for endogenous intestinal N-nitrosation arising from red meat. Cancer Res 63:2358–2360. Daniel C, Cross A, Koebnick C, Sinha R. 2011. Trends in meat consumption in the United States. Public Health Nutr 14: 575–583. Danowska-Oziewicz M. 2009. The influence of cooking method on the quality of pork patties. J Food Procc Preser 33:473–485. Dobrikova E, Svetlikowa S. 2007. Occurrence of benzo[a]pyrene in some foods of animal origin in the Slovak Republic. J Food Nutr Res 46: 181–185. Essumang D, Dodoo D, Adjei J. 2012. Polycyclic aromatic hydrocarbon (PAH) contamination in smoke-cured fish products. J Food Comp Anal 27:128–138. Farhadian A, Jinap S, Faridah Zaidu I. 2012. Effects of marinating on the formation of polycyclicaromatic hydrocarbons (benzo(a)pyrene, benzo(b)fluoranthene and fluoranthene) in grilled beef meet. Food Control 28:420–425. Ferguson L. 2010. Meat and cancer. Meat Sci 84:308–313. Ferrucci L, Sinha R, Ward H, Graubard B, Hollenbeck A, Kilfoy B, Schatzkin A, et al. 2010. Meat and components of meat and the risk of bladder cancer in the NIH-AARP diet and health study. Cancer 116: 4345–4353. Food and Agriculture Organization. 2009. The state of food and agriculture. Rome, Italy: FAO. Gibis M. 2007. Effect of oil marinades with garlic, onion, and lemon juice on the formation of heterocyclic aromatic amines in fried beef patties. J Agric Food Chem 55:10240–10247. Giovannucci E, Rimm E, Stampfer M, Colditz G, Ascherio A, Willet W. 1994. Intake of fat, meat and fiber in relation to risk of colon cancer in men. Cancer Res 54:2390–2397. Hebels D, Sveje K, de Kok M, van Herwijnen M, Kuhnle G, Engels L, Vleugels-Simon C, et al. 2011. N-nitroso compound exposureassociated transcriptomic profiles are indicative of an increased risk for colorectal cancer. Cancer Lett 309:1–10. Hitzel A, Poehlmann M, Schwaegele F, Speer K, Jira W. 2013. Polycyclic aromatic hydrocarbons (PAH) and phenolic substances in meat products smoked with different types of wood and smoking spices. Food Chem 139:955–962. Holtrop G, Johnstone A, Fyfe C, Gratz S. 2012. Diet composition is associated with endogenous formation of N-Nitroso compounds in obese men. J Nutr 142:1652–1658.


Ja¨gerstad M, Skog K, Arvidsson P, Solyakov A. 1998. Chemistry, formation and occurrence of genotoxic heterocyclic amines identified in model systems and cooked foods. Z Lebensm Unters Forsch A 207: 419–427. Jahurul H, Jinap S, Ang S, Abdul-Hamid A, Hajeb P, Lioe H, Zaidul I. 2010. Dietary exposure to heterocyclic amines in high-temperature cooked meat and fish in Malaysia. Food Addit Contam: Part A 27: 1060–1071. Joosen A, Kuhnle G, Aspinall S, Barrow T, Lecommandeur E, Azqueta A, Collins A, Bingham S. 2009. Effect of processed and red meat on endogenous nitrosation and DNA damage. Carcinogenesis 30: 1402–1407. Kelley J, Duggan J. 2003. Gastric cancer epidemiology and risk factors. J Clin Epid 56:1–9. Keszei A, Goldbohm R, Schouten L, Jakszyn P, van den Brandt P. 2013. Dietary N-nitroso compounds, endogenous nitrosation, and the risk of esophageal and gastric cancer subtypes in the Netherlands Cohort Study. Am J Clin Nutr 97:135–146. Koeth R, Wang Z, Levison B, Buffa J, Org E, Sheehy B, Britt E, et al. 2013. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 19:576–585. Kikugawa K. 2004. Prevention of mutagen formation in heated meats and model systems. Mutagenesis 19:431–439. Kim E, Coelho D, Blachier F. 2013. Review of the association between meat consumption and risk of colorectal cancer. Nutr Res 33:983–999. Kinze M, Salmon C, Paris P, Felton J. 1999. Food heating and the formation of heterocyclic aromatic amine and polycyclic aromatic hydrocarbon mutagens/carcinogens. Adv Exp Med Biol 459:179–193. Koushik A, Hunter D, Spiegelman D, Beeson W, van den Brandt P, Buring J, Calle E, et al. 2007. Fruits, vegetables, and colon cancer risk in a pooled analysis of 14 cohort studies. J Natl Cancer Inst 99: 1471–1483. Kuhnle G, Story G, Reda T, Mani A, Moore K, Lunn J, Bingham S. 2007. Diet-induced endogenous formation of nitroso compounds in the GI tract. Free Radic Biol Med 43:1040–1047. Larsson S, Wolk A. 2006. Meat consumption and risk of colorectal cancer: a meta-analysis of prospective studies. Int J Cancer 119: 2657–2664. Lee H, Jiaan C, Tsai S. 1992. Flavone inhibits mutagen formation during heating in a glycine/creatinine/glucose model system. Food Chem 45: 235–248. Liao G, Wang G, Xu X, Zhou G. 2010. Effect of cooking methods on the formation of heterocyclic aromatic amines in chicken and duck breast. Meat Sci 85:149–154. Lijinsky W. 1992. Chemistry and biology of N-nitroso compounds. Cambridge: Cambridge University Press. Linos E, Willett W, Cho E, Colditz G, Frazier L. 2008. Red meat consumption during adolescence among premenopausal women and risk of breast cancer. Cancer Epidemiol Biomark Prev 17:2146–2151. Loh Y, Jakszyn P, Luben R, Mulligan A, Mitrou P, Khaw K. 2011. N-nitroso compounds and cancer incidence: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study. Am J Clin Nutr 93:1053–1061. Lu¨cke F, Trafialek J. 2010. Umsetzung der HACCP – prinzipen in fleisch verarbeitenden betrieben in Polen ins in Deutschland. Fleischwirtschaft 90:43–45. McAfee A, McSorley E, Cuskelly G, Moss B, Wallace J, Bonham M, Fearon A. 2010. Red meat consumption: an overview of the risks and benefits. Meat Sci 84:1–13. McKenna D, Lorenzen C, Pollol K, Morgan W, Mies W, Harris J, Murphy R, et al. 2004. Interrelationships of breed type, USDA quality grade, cooking method and degree of doneness on consumer evaluations of beef in Dallas and San Antonio, Texas, USA. Meat Sci 66:399–406. Mozaffarian D, Micha R, Wallace S. 2010. Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Med 7:e1000252. Murkovic M, Steinberger D, Pfannhauser W. 1998. Antioxidant spices reduce the formation of heterocyclic amines in fried meat. Z Lebensm Unters Forsch A 207:477–480. Pan A, Sun Q, Bernstein A, Schulze M, Manson J, Stampfer M, Willett C, Hu F. 2012. Red meat consumption and mortality: results from 2 prospective cohort studies. Arch Int Med 172:555–563. Parr C, Hjartaker A, Lund E, Veierod M. 2013. Meat intake, cooking methods and risk of proximal colon, distal colon and rectal cancer: the


DOI: 10.3109/09637486.2014.917146

Norwegian Women and Cancer (NOWAC) cohort study. Int J Cancer 133:1153–1163. Parzefall W. 2008. Minireview on the toxicity of dietary acrylamide. Food Chem Toxicol 46:1360–1364. Phillips D. 1999. Polycyclic aromatic hydrocarbons in the diet. Mutat Res 443:139–147. Reicks A, Brooks J, Garmyn A, Thompson L, Miller M. 2011. Demographics and beef preferences affect consumer motivation for purchasing fresh beef steaks and roasts. Meat Sci 87:403–411. Rohrmann S, Hermann S, Linseisen J. 2009. Heterocyclic aromatic amine intake increases colorectal adenoma risk: finding from a prospective European cohort study. Am J Clin Nutr 89:1418–1424. Salmon C, Knize M, Panteleakos F, Wu R, Nelson D, Felton J. 2000. Minimization of heterocyclic amines and thermal inactivation of Escherichia coli in fried ground beef. J Natl Cancer Inst 92:1773–1778. Sandhu M, White I, McPherson K. 2001. Systematic review of the prospective cohort studies on meat consumption and colorectal cancer risk: a meta-analytical approach. Cancer Epid Biomark Prev 10: 439–446. Shrestha S, Cornforth D, Nummer B. 2010. Process optimization and consumer acceptability of salted ground beef patties cooked and held hot in flavored marinade. J Food Sci 75:607–612. Sinha R, Chow W, Kulldorff M, Denobile J, Butler J, Garcia-Closas M, Weil R, et al. 1999. Well-done, grilled red meat increases the risk of colorectal adenomas. Cancer Res 59:4320–4324. Skog K, Johansson M, Ja¨gerstad M. 1998. Carcinogenic heterocyclic amines in model systems and cooked foods: a review on formation, occurrence and intake. Food Chem Toxicol 36:879–896. Skog K, Solyakov A. 2002. Heterocyclic amines in poultry products: a literature review. Food Chem Toxicol 40:1213–1221. Steck S, Gaudet M, Eng S, Britton J, Teitelbaum S, Neugut A, Santella R, Gammon M. 2007. Cooked meat and risk of breast cancer – lifetime versus recent dietary intake. Epidemiology 18:373–382. Stolyhwo A, Sikorski Z. 2005. Polycyclic aromatic hydrocarbons in smoked fish – a critical review. Food Chem 91:303–311. Sugimura T. 2000. Nutrition and dietary carcinogens. Carcinogenesis 21: 387–395.


7

Sugimura T, Wakabayashi K, Nakagama H, Nagao M. 2004. Heterocyclic amines: mutagens/carcinogens produced during cooking of meat and fish. Cancer Sci 95:290–299. Tai C, Lee K, Chen B. 2001. Effects of various additives on the formation of heterocyclic amines in fried fish fibre. Food Chem 75:309–316. Trafialek J, Przybylski W. 2011. Analysis of risk exposure to carcinogenic diseases from pork meat. Fleischwirtschaft Int 26:73–78. Tran L, Salmon C, Knize M, Colvin M. 2002. Experimental and simulation studies of heat flow and heterocyclic amine mutagen/ carcinogen formation in pan-fried meat patties. Food Chem Toxicol 40: 673–684. Truswell A. 2002. Meat consumption and cancer of the large bowel. Eur J Clin Nutr 56:S19–S24. Turesky R. 2007. Formation and biochemistry of carcinogenic heterocyclic aromatic amines in cooked meats. Toxicol Lett 168:219–227. Turesky R, Le Marchand L. 2011. Metabolism and biomarkers of heterocyclic aromatic amines in molecular epidemiology studies: lessons learned from aromatic amines. Chem Res Toxicol 24: 1169–1214. van Duijnhoven F, Bueno-De-Mesquita H, Ferrari P, Jenab M, Boshuizen H, Ros M, Asagrande C, et al. 2009. Fruit, vegetables, and colorectal cancer risk: the European Prospective Investigation into cancer and nutrition. Am J Clin Nutr 89:1441–1452. Weisburger J. 2002. Comments on the history and importance of aromatic and heterocyclic amines in public health. Mutat Res 506–507:9–20. World Cancer Research Fund/American Institute for Cancer Research. 2007. Food, nutrition, physical activity and the prevention of cancer: a global perspective. Washington, DC: American Institute for Cancer Research. Zheng W, Lee S. 2009. Well-done meat intake, heterocyclic amine exposure, and cancer risk. Nutr Cancer 61:437–446. Zheng W, Gustafson D, Sinha R, Cerhan J, Moore D, Hong C, Anderson K, et al. 1998. Well-done meat intake and the risk of breast cancer. J Natl Cancer Inst 90:1724–1729. Zimmerli B, Rhyn P, Zoller O, Schlatter J. 2001. Occurrence of heterocyclic aromatic amines in the Swiss diet: analytical method, exposure estimation and risk assessment. Food Addit Contam 18: 533–551.