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Heterocyclic amines are a group of chemical compounds, many of which can be formed during cooking. They are found in meats that are cooked to the "well done" stage, in pan drippings and in meat surfaces that show a brown or black crust. Epidemiological studies show associations between intakes of heterocyclic amines and cancers of the colon, rectum, breast, prostate, pancreas, lung, stomach, and esophagus, and animal feeding experiments support a causal relationship. The U.S. Department of Health and Human Services Public Health Service labeled several heterocyclic amines as likely carcinogens in its 13th Report on Carcinogens. [1] Changes in cooking techniques reduce the level of heterocyclic amines.
More than 20 compounds fall into the category of heterocyclic amines, often abbreviated HCAs . Table 1 shows the chemical name and abbreviation of those most commonly studied.
Chemical name | Abbreviation | Year discovered |
---|---|---|
2-Amino-3-methylimidazo[4,5-f]quinoline | IQ | 1980 |
2-Amino-3,4-dimethylimidazo[4,5-f]quinoline | MeIQ | 1980 |
2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline | MeIQx | 1981 |
2-Amino-1-methyl-6-phenylimiazo[4,5-b]pyridine | PhIP | 1986 |
All four of these compounds are included in the 13th Report on Carcinogens. [1]
The compounds found in food are formed when creatine (a non-protein amino acid found in muscle tissue), other amino acids and monosaccharides are heated together at high temperatures (125-300o C or 275-572o F) or cooked for long periods. HCAs form at the lower end of this range when the cooking time is long; at the higher end of the range, HCAs are formed within minutes. [3]
A review of 14 studies of HCA content in ground beef cooked under home conditions found in northern Europe and the U.S. found a range of values (Table 2). Because a standard U.S. serving of meat is 3 ounces, Table 2 includes a projection of the maximum amount of HCAs that could be found in a ground beef patty.
HCA | Amount, ng/g | Maximum amount in 3 ounces of ground beef (in ng) |
---|---|---|
IQ | n.d.-1.6 | 136 |
MeIQ | n.d.-1.7 | 145 |
MeIQx | n.d.-16.4 | 1395 |
PhIP | n.d.-68 | 5783 |
(n.d.= none detected)
Meat is a major component of American diets. Data from 1960 show the combined annual per capita consumption of beef, pork and chicken at 148 pounds; in 2004, that amount increased to 195 pounds a year. [4] Ground beef made up 42% of the beef market in 2000. Beef consumption, particularly ground and processed beef, is highest in households with incomes at or below 130 percent of the poverty level.
Patterns of beef intake by race/ethnicity show that non-Hispanic whites and Asians consumed the least amount of beef. Non-Hispanic African-Americans had the highest per capita intake of processed beef, ground beef and steaks compared to three other race/ethnicity groups. [4]
More than half of beef purchased in the U.S. comes from retail stores and is prepared at home. Ground beef makes up the highest per capita intakes of beef both at home and away from home.
Ground beef consumption is highest among males age 12-19 who consume on average 50 pounds per year per capita. The 12-19 age group showed the highest consumption of ground beef for females, but the amount (28.5 lbs) is much lower than that of males. [4]
US dietary exposure has been estimated at 1-17 ng/kg bodyweight per day. [5] Table 3 shows the average daily lifetime consumption of HCAs for subgroups of the U.S. population. [6] This analysis was based on the food intake data of 27215 people participating in the 1994 to 1996 Continuing Survey of Food Intakes by Individuals (CSFII) survey. Approximately 16 percent of HCA exposure came from hamburgers.
HCA type | Lifetime average intake - All, ng/day | Lifetime average intake - All men, ng/kg/day |
---|---|---|
PhIP | 6.0 | 6.2 |
MeIQx | 1.1 | 1.2 |
DiMeQx | 0.20 | 0.21 |
IQ | 0.23 | 0.18 |
African American males had 50-100% higher intakes than white males and African American males consumed three times as many HCAs as white males (Table 4). [6]
HCA type | White | African American | Asian/Pacific Islander |
---|---|---|---|
PhIP | 6.1 | 12.0 | 10.0 |
MeIQx | 1.2 | 1.8 | 1.9 |
DiMeQx | 0.23 | 0.51 | 0.27 |
IQ | 0.16 | 0.24 | 0.29 |
HCA formation during cooking depends on the type of meat, cooking temperature, the degree of browning and the cooking time. Meats that are lower in fat and water content show higher concentrations of HCAs after cooking. More HCAs are formed when pan surface temperatures are higher than 220 °C (428 °F) such as with most frying or grilling. However, HCAs also form at lower temperatures when the cooking time is long, as in roasting. HCA concentrations are higher in browned or burned crusts that result from high temperature. [3] The pan drippings and meat bits that remain after meat is fried have high concentrations of HCAs. Beef, chicken and fish have higher concentrations than pork. Sausages are high in fat and water and show lower concentrations. [7]
Ground beef patties show lower levels of HCAs if they are flipped every minute until the target temperature is reached. [8] Beef patties cooked while frozen show no difference in HCA levels compared to room-temperature patties. [9]
After scientists discovered the carcinogenic components in cigarette smoke, they questioned whether carcinogens could also be found in smoked/burned foods, such as meats. [2] In 1977, cancer-causing compounds heterocyclic amines were discovered in food as a result of household cooking processes. [2] [10]
The most potent of the HCAs, MeIQ, is almost 24 times more carcinogenic than aflatoxin, a carcinogen produced by mold. [2]
Most of the 20 HCAs are more toxic than benzopyrene, a carcinogen found in cigarette smoke and coal tar. MeIQ, IQ and 8-MeIQx are the most potent mutagens according to the Ames test. [11] These HCAs are 100 times more potent carcinogens than PhIP, the compound most commonly found as a result of normal cooking. [11] [12]
HCAs contribute to the development of cancer by causing gene mutations, causing new cells to grow in an uncontrolled manner and form a tumor. Epidemiological studies linked consumption of well-done meats with increased risk of certain cancers, including cancer of the colon or rectum. [13] A review of research articles on meat consumption and colon cancer estimated that red meat consumption contributed to 7 to 9% of colon cancer cases in European men and women.[ citation needed ]
Long-term rat studies showed that PhIP causes cancer of the colon and mammary gland in rats. [12] Female rats given doses of 0, 12.4, 25, 50, 100 or 200 ppm of PhIP showed a dose-dependent incidence of adenocarcinomas. The offspring of female rats exposed to PhIP while pregnant had a higher prevalence of adenocarcinomas than those whose mothers had not been exposed. This was true even for offspring who were not exposed to PhIP. PhIP was transferred from mothers to offspring in their milk.
The effects of HCAs and well-done cooked meat on humans are less well established. Meat consumption, especially of well-done meat and meat cooked at a high temperature, can be used as an indirect measure of exposure to HCAs. A review of all research studies reported between 1996 and 2007 that examined relationships between HCAs, meat and cancer. [14] Twenty-two studies were found; of these, 18 showed a relationship between either meat intake or HCA exposure and some form of cancer. HCA exposure was measured in 10 of the studies and of those, 70% showed an association with cancer. The authors concluded that high intake of well-done meat and/or high exposure to certain HCAs may be associated with cancer of the colon, breast, prostate, pancreas, lung, stomach and esophagus.
A recent study found that the relative risk for colorectal cancer increased at intakes >41.4 ng/day. [15] Some evidence of increased relative risk occurred with intakes of MeIQx greater than or equal to 19.9 ng/day, but the trend was not as strong as for PhIP.
Recent studies had mixed results, finding no relationship between dietary heterocyclic amines and lung cancer in women who had never smoked, [16] no relationship between HCA intake and prostate cancer risk, [17] but suggesting a positive association between red meat, PhIP and bladder cancer [18] and increased risk of advanced prostate cancer with intakes of meat cooked at high temperatures. [19]
Although not all studies report an association between HCA and/or meat intake and cancers, the U.S. Department of Health and Human Services Public Health Service National Toxicology Program found sufficient evidence to label four HCAs as "reasonably anticipated to be a human carcinogen" in its twelfth Report on Carcinogens, published in 2011. The HCA known as IQ was first listed in the tenth report in 2002. MeIQ, MeIQx and PhIP were added to the list of anticipated carcinogens in 2004. [5] The Report on Carcinogens stated that MeIQ has been associated with rectal and colon cancer, MeIQx with lung cancer, IQ with breast cancer and PhIP with stomach and breast cancer. [5] However, no current federal guidelines focus on the recommended consumption limit of HCA levels in meat. [20]
Cooking, also known as cookery or professionally as the culinary arts, is the art, science and craft of using heat to make food more palatable, digestible, nutritious, or safe. Cooking techniques and ingredients vary widely, from grilling food over an open fire, to using electric stoves, to baking in various types of ovens, reflecting local conditions.
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substances are considered carcinogens, but their carcinogenic activity is attributed to the radiation, for example gamma rays and alpha particles, which they emit. Common examples of non-radioactive carcinogens are inhaled asbestos, certain dioxins, and tobacco smoke. Although the public generally associates carcinogenicity with synthetic chemicals, it is equally likely to arise from both natural and synthetic substances. Carcinogens are not necessarily immediately toxic; thus, their effect can be insidious.
Dairy products or milk products, also known as lacticinia, are food products made from milk. The most common dairy animals are cow, water buffalo, nanny goat, and ewe. Dairy products include common grocery store food around the world such as yogurt, cheese, milk and butter. A facility that produces dairy products is known as a dairy. Dairy products are consumed worldwide to varying degrees. Some people avoid some or all dairy products because of lactose intolerance, veganism, or other health reasons or beliefs.
Meat is animal flesh that is eaten as food. Humans have hunted, farmed, and scavenged other animals for meat since prehistoric times. The establishment of settlements in the Neolithic Revolution allowed the domestication of animals such as chickens, sheep, rabbits, pigs, and cattle. This eventually led to their use in meat production on an industrial scale in slaughterhouses.
In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in animals, such mutagens can therefore be carcinogens, although not all necessarily are. All mutagens have characteristic mutational signatures with some chemicals becoming mutagenic through cellular processes.
Marinating is the process of soaking foods in a seasoned, often acidic, liquid before cooking. The origin of the word alludes to the use of brine in the pickling process, which led to the technique of adding flavor by immersion in liquid. The liquid in question, the marinade, can be either acidic or enzymatic, or have a neutral pH. In addition to these ingredients, a marinade often contains oils, herbs, and spices to further flavor the food items.
Grilling is a form of cooking that involves heat applied to the surface of food, commonly from above, below or from the side. Grilling usually involves a significant amount of direct, radiant heat, and tends to be used for cooking meat and vegetables quickly. Food to be grilled is cooked on a grill, using a cast iron/frying pan, or a grill pan.
Benzo[a]pyrene (BaP or B[a]P) is a polycyclic aromatic hydrocarbon and the result of incomplete combustion of organic matter at temperatures between 300 °C (572 °F) and 600 °C (1,112 °F). The ubiquitous compound can be found in coal tar, tobacco smoke and many foods, especially grilled meats. The substance with the formula C20H12 is one of the benzopyrenes, formed by a benzene ring fused to pyrene. Its diol epoxide metabolites, more commonly known as BPDE, react with and bind to DNA, resulting in mutations and eventually cancer. It is listed as a Group 1 carcinogen by the IARC. In the 18th century a scrotal cancer of chimney sweepers, the chimney sweeps' carcinoma, was already known to be connected to soot.
In organic chemistry, nitrosamines are organic compounds with the chemical structure R2N−N=O, where R is usually an alkyl group. They feature a nitroso group bonded to a deprotonated amine. Most nitrosamines are carcinogenic in nonhuman animals. A 2006 systematic review supports a "positive association between nitrite and nitrosamine intake and gastric cancer, between meat and processed meat intake and gastric cancer and oesophageal cancer, and between preserved fish, vegetable and smoked food intake and gastric cancer, but is not conclusive".
Pancetta is a salt-cured pork belly meat, product in a category known as salume. In Italy, it is often used to add depth to soups and pastas.
In gastronomy, red meat is commonly red when raw, in contrast to white meat, which is pale in color before cooking. In culinary terms, only flesh from mammals or fowl is classified as red or white. In nutritional science, red meat is defined as any meat that has more of the protein myoglobin than white meat. White meat is defined as non-dark meat from fish or chicken.
Processed meat is considered to be any meat that has been modified in order to either improve its taste or to extend its shelf life. Methods of meat processing include salting, curing, fermentation, smoking, boiling, frying, and/or the addition of chemical preservatives. Processed meat is usually composed of pork or beef or, less frequently, poultry. It can also contain offal or meat by-products such as blood. Processed meat products include bacon, ham, sausages, salami, corned beef, jerky, hot dogs, lunch meat, canned meat, chicken nuggets, and meat-based sauces. Meat processing includes all the processes that change fresh meat with the exception of simple mechanical processes such as cutting, grinding or mixing.
The International Agency for Research on Cancer is an intergovernmental agency forming part of the World Health Organization of the United Nations. Its role is to conduct and coordinate research into the causes of cancer. It also collects and publishes surveillance data regarding the occurrence of cancer worldwide.
In culinary terms, white meat is meat which is pale in color before and after cooking. In traditional gastronomy, white meat also includes rabbit, the flesh of milk-fed young mammals, and sometimes pork. In ecotrophology and nutritional studies, white meat includes poultry and fish, but excludes all mammal flesh, which is considered red meat.
Curing is any of various food preservation and flavoring processes of foods such as meat, fish and vegetables, by the addition of salt, with the aim of drawing moisture out of the food by the process of osmosis. Because curing increases the solute concentration in the food and hence decreases its water potential, the food becomes inhospitable for the microbe growth that causes food spoilage. Curing can be traced back to antiquity, and was the primary method of preserving meat and fish until the late 19th century. Dehydration was the earliest form of food curing. Many curing processes also involve smoking, spicing, cooking, or the addition of combinations of sugar, nitrate, and nitrite.
Heterocyclic amines, also sometimes referred to as HCAs, are chemical compounds containing at least one heterocyclic ring, which by definition has atoms of at least two different elements, as well as at least one amine (nitrogen-containing) group. Typically it is a nitrogen atom of an amine group that also makes the ring heterocyclic, though compounds exist in which this is not the case. The biological functions of heterocyclic amines vary, including vitamins and carcinogens. Carcinogenic heterocyclic amines are created by high temperature cooking of meat and smoking of plant matter like tobacco. Some well known heterocyclic amines are niacin, nicotine, and the nucleobases that encode genetic information in DNA.
In molecular genetics, a DNA adduct is a segment of DNA bound to a cancer-causing chemical. This process could lead to the development of cancerous cells, or carcinogenesis. DNA adducts in scientific experiments are used as biomarkers of exposure. They are especially useful in quantifying an organism's exposure to a carcinogen. The presence of such an adduct indicates prior exposure to a potential carcinogen, but it does not necessarily indicate the presence of cancer in the subject animal.
Dietary factors are recognized as having a significant effect on the risk of cancers, with different dietary elements both increasing and reducing risk. Diet and obesity may be related to up to 30–35% of cancer deaths, while physical inactivity appears to be related to 7% risk of cancer occurrence.
A co-carcinogen is a chemical that promotes the effects of a carcinogen in the production of cancer. Usually, the term is used to refer to chemicals that are not carcinogenic on their own, such that an equivalent amount of the chemical is insufficient to initiate carcinogenesis. A chemical can be co-carcinogenic with other chemicals or with nonchemical carcinogens, such as UV radiation.
PhIP (2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) is one of the most abundant heterocyclic amines (HCAs) in cooked meat. PhIP is formed at high temperatures from the reaction between creatine or creatinine, amino acids, and sugar. PhIP formation increases with the temperature and duration of cooking and also depends on the method of cooking and the variety of meat being cooked. The U.S. Department of Health and Human Services National Toxicology Program has declared PhIP as "reasonably anticipated to be a human carcinogen". International Agency for Research on Cancer (IARC), part of World Health Organization, has classified PhIP as IARC Group 2B carcinogen. There is sufficient evidence in experimental animals, as well as in vitro models, for the carcinogenicity of PhIP.
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