Heterocyclic amine formation in meat

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A well-done steak, with accompaniments. The black lines where it has rested on the grill will contain heterocyclic amines. Thanksgiving steak risotto.jpg
A well-done steak, with accompaniments. The black lines where it has rested on the grill will contain heterocyclic amines.

Heterocyclic amines (HCAs) 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.

Contents

Compounds

More than 20 compounds fall into the category of heterocyclic amines. [2] Table 1 shows the chemical name and abbreviation of those most commonly studied.

Table 1. Chemical names and abbreviations for HCAs [3]
Chemical nameChemical structureAbbreviationYear discovered
2-Amino-3-methylimidazo[4,5-f]quinoline IQ.svg IQ1980
2-Amino-3,4-dimethylimidazo[4,5-f]quinoline MeIQ structure.svg MeIQ1980
2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline MeIQx.svg MeIQx1981
2-Amino-1-methyl-6-phenylimiazo[4,5-b]pyridine PhIP.svg PhIP1986

All four of these compounds are included in the 13th Report on Carcinogens. [1]

Meat

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 (125-300 °C or 275-572 °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. [4]

Cooked ground beef

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.

Table 2. Content of four HCAs in ground beef
HCAAmount, ng/gMaximum amount in 3 ounces of ground beef (in ng)
IQn.d.-1.6136
MeIQn.d.-1.7145
MeIQxn.d.-16.41395
PhIPn.d.-685783

(n.d.= none detected)

United States

Meat consumption in the U.S. Meat Consumption in the U.S..jpg
Meat consumption in the U.S.

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. [5] 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. [5]

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. [5]

US dietary exposure has been estimated at 1-17 ng/kg bodyweight per day. [6] Table 3 shows the average daily lifetime consumption of HCAs for subgroups of the U.S. population. [7] 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.

Table 3. Lifetime average weighted intake of four HCAs by men and women in the U.S.
HCA typeLifetime average intake - All, ng/dayLifetime average intake - All men, ng/kg/day
PhIP6.06.2
MeIQx1.11.2
DiMeQx0.200.21
IQ0.230.18

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). [7]

Table 4. Estimated mean intakes of HCAs among children under 16 by ethnicity, ng/kg/day
HCA typeWhiteAfrican AmericanAsian/Pacific Islander
PhIP6.112.010.0
MeIQx1.21.81.9
DiMeQx0.230.510.27
IQ0.160.240.29

Cooking

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. [4] 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. [8]

Ground beef patties show lower levels of HCAs if they are flipped every minute until the target temperature is reached. [9] Beef patties cooked while frozen show no difference in HCA levels compared to room-temperature patties. [10]

Cancer

After scientists discovered the carcinogenic components in cigarette smoke, they questioned whether carcinogens could also be found in smoked/burned foods, such as meats. [3] In 1977, cancer-causing compounds heterocyclic amines were discovered in food as a result of household cooking processes. [3] [11]

The most potent of the HCAs, MeIQ, is almost 24 times more carcinogenic than aflatoxin, a carcinogen produced by mold. [3]

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. [12] These HCAs are 100 times more potent carcinogens than PhIP, the compound most commonly found as a result of normal cooking. [12] [13]

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. [14] 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 ]

Animal studies

Long-term rat studies showed that PhIP causes cancer of the colon and mammary gland in rats. [13] 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.

Epidemiological studies

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. [15] 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. [16] 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, [17] no relationship between HCA intake and prostate cancer risk, [18] but suggesting a positive association between red meat, PhIP and bladder cancer [19] and increased risk of advanced prostate cancer with intakes of meat cooked at high temperatures. [20]

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. [6] 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. [6] However, no current federal guidelines focus on the recommended consumption limit of HCA levels in meat. [21]

Related Research Articles

<span class="mw-page-title-main">Cooking</span> Preparing food using heat

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. Cooking is an aspect of all human societies and a cultural universal.

<span class="mw-page-title-main">Carcinogen</span> Substance, radionuclide, or radiation directly involved in causing cancer

A carcinogen is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruses and bacteria. Most carcinogens act by creating mutations in DNA that disrupt a cell's normal processes for regulating growth, leading to uncontrolled cellular proliferation. This occurs when the cell's DNA repair processes fail to identify DNA damage allowing the defect to be passed down to daughter cells. The damage accumulates over time. This is typically a multi-step process during which the regulatory mechanisms within the cell are gradually dismantled allowing for unchecked cellular division.

<span class="mw-page-title-main">Meat</span> Animal flesh eaten as food

Meat is animal tissue, often muscle, that is eaten as food. Humans have hunted and farmed other animals for meat since prehistory. The Neolithic Revolution allowed the domestication of vertebrates, including chickens, sheep, goats, pigs, horses, and cattle, starting around 11,000 years ago. Since then, selective breeding has enabled farmers to produce meat with the qualities desired by producers and consumers.

<span class="mw-page-title-main">Mutagen</span> Physical or chemical agent that increases the rate of genetic mutation

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.

<span class="mw-page-title-main">Grilling</span> Form of cooking that involves dry heat

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.

<span class="mw-page-title-main">Smoking (cooking)</span> Exposing food to smoke to flavor or preserve it

Smoking is the process of flavoring, browning, cooking, or preserving food, particularly meat, fish and tea, by exposing it to smoke from burning or smoldering material, most often wood.

Acrylamide (or acrylic amide) is an organic compound with the chemical formula CH2=CHC(O)NH2. It is a white odorless solid, soluble in water and several organic solvents. From the chemistry perspective, acrylamide is a vinyl-substituted primary amide (CONH2). It is produced industrially mainly as a precursor to polyacrylamides, which find many uses as water-soluble thickeners and flocculation agents.

Benzo(<i>a</i>)pyrene Carcinogenic compound found in smoke and soot

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.

<span class="mw-page-title-main">Nitrosamine</span> Organic compounds of the form >N–N=O

Nitrosamines are organic compounds produced by industrial processes.

<span class="mw-page-title-main">Red meat</span> Meat which is red when raw, with high myoglobin content

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.

<span class="mw-page-title-main">Processed meat</span> Type of meat

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, 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.

<span class="mw-page-title-main">Alcohol and cancer</span> Relationship between cancer and the consumption of alcohol

Alcohol and cancer have a complex relationship. Alcohol causes cancers of the oesophagus, liver, breast, colon, oral cavity, rectum, pharynx, and larynx, and probably causes cancers of the pancreas. Cancer risk can occur even with light to moderate drinking. The more alcohol is consumed, the higher the cancer risk, and no amount can be considered completely safe.

<span class="mw-page-title-main">Curing (food preservation)</span> Food preservation and flavouring processes based on drawing moisture out of the food by osmosis

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.

<span class="mw-page-title-main">Heterocyclic amine</span> Any heterocyclic compound having at least one nitrogen heteroatom

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.

<span class="mw-page-title-main">DNA adduct</span> Segment of DNA bound to a cancer-causing chemical

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.

<span class="mw-page-title-main">Diet and cancer</span> Connections between dietary habits and cancer

Many dietary recommendations have been proposed to reduce the risk of cancer, few have significant supporting scientific evidence. Obesity and drinking alcohol have been correlated with the incidence and progression of some cancers. Lowering the consumption of sweetened beverages is recommended as a measure to address obesity.

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.

<span class="mw-page-title-main">2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine</span> Chemical compound


2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is one of the most abundant heterocyclic amines (HCAs) found 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.

<span class="mw-page-title-main">Cancer prevention</span> Taking measures to decrease cancer incidence

Cancer prevention is the practice of taking active measures to decrease the incidence of cancer and mortality. The practice of prevention depends on both individual efforts to improve lifestyle and seek preventive screening, and socioeconomic or public policy related to cancer prevention. Globalized cancer prevention is regarded as a critical objective due to its applicability to large populations, reducing long term effects of cancer by promoting proactive health practices and behaviors, and its perceived cost-effectiveness and viability for all socioeconomic classes.

References

  1. 1 2 13th Report on Carcinogens. "Substances Listed in the Thirteenth Report on Carcinogens" (PDF). Retrieved 2015-05-08.{{cite web}}: CS1 maint: numeric names: authors list (link)
  2. ↑ Eisenbrand, G.; Tang, W. (1993). "Food-borne heterocyclic amines. Chemistry, formation, occurrence and biological activities. A literature review". Toxicology. 84 (1–3): 1–82. Bibcode:1993Toxgy..84....1E. doi:10.1016/0300-483X(93)90109-6. PMID   8266331.
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  6. 1 2 3 U.S. Department of Health and Human Services Public Health Service, National Toxicology Program. (2011). Report on Carcinogens, 12th ed.
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  8. ↑ Augustsson, Katarina; Lindblad, Jennifer; Overvik, Eva; Steineck, Gunnar (1999-05-01). "A population-based dietary inventory of cooked meat and assessment of the daily intake of food mutagens". Food Additives & Contaminants. 16 (5): 215–225. doi:10.1080/026520399284082. ISSN   0265-203X. PMID   10560575.
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  10. ↑ Persson, Elna; Oroszvári, Bea Kovácsné; Tornberg, Eva; Sjöholm, Ingegerd; Skog, Kerstin (2008-01-01). "Heterocyclic amine formation during frying of frozen beefburgers". International Journal of Food Science & Technology. 43 (1): 62–68. doi:10.1111/j.1365-2621.2006.01390.x. ISSN   1365-2621.
  11. ↑ Norat, Teresa; Lukanova, Annekatrin; Ferrari, Pietro; Riboli, Elio (2002-03-10). "Meat consumption and colorectal cancer risk: dose-response meta-analysis of epidemiological studies". International Journal of Cancer. 98 (2): 241–256. doi: 10.1002/ijc.10126 . ISSN   0020-7136. PMID   11857415.
  12. 1 2 Turesky, Robert J. (2007-02-05). "Formation and biochemistry of carcinogenic heterocyclic aromatic amines in cooked meats". Toxicology Letters. Highlights of EUROTOX 2006/6 CTDC Congress - 43rd Congress of the European Societies of Toxicology & 6th Congress of Toxicology in Developing Countries. 168 (3): 219–227. doi:10.1016/j.toxlet.2006.10.018. PMID   17174486.
  13. 1 2 Nobuyuki, I; Hasegawa, R; Imaidi, K; Tamano, S; Hagiwara, A; Hirose, M; Shirai, T. (1997). "Carcinogenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the rat". Mutation Research. 376 (1–2): 107–114. Bibcode:1997MRFMM.376..107I. doi:10.1016/S0027-5107(97)00032-8. PMID   9202745.
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  15. ↑ Zheng, Wei; Lee, Sang-Ah (2009-07-17). "Well-Done Meat Intake, Heterocyclic Amine Exposure, and Cancer Risk". Nutrition and Cancer. 61 (4): 437–446. doi:10.1080/01635580802710741. ISSN   0163-5581. PMC   2769029 . PMID   19838915.
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  17. ↑ Lim, Wei-Yen; Chuah, Khoon Leong; Eng, Philip; Leong, Swan Swan; Lim, Elaine; Lim, Tow Keang; Ng, Alan; Poh, Wee Teng; Tee, Augustine (2011-08-01). "Meat Consumption and Risk of Lung Cancer Among Never-Smoking Women". Nutrition and Cancer. 63 (6): 850–859. doi:10.1080/01635581.2011.589961. ISSN   0163-5581. PMID   21774592. S2CID   45306028.
  18. ↑ Sander, Anja; Linseisen, Jakob; Rohrmann, Sabine (2010-11-20). "Intake of heterocyclic aromatic amines and the risk of prostate cancer in the EPIC-Heidelberg cohort" (PDF). Cancer Causes & Control. 22 (1): 109–114. doi:10.1007/s10552-010-9680-9. ISSN   0957-5243. PMID   21103922. S2CID   29236937.
  19. ↑ Ferrucci, Leah M.; Sinha, Rashmi; Ward, Mary H.; Graubard, Barry I.; Hollenbeck, Albert R.; Kilfoy, Briseis A.; Schatzkin, Arthur; Michaud, Dominique S.; Cross, Amanda J. (2010-09-15). "Meat and components of meat and the risk of bladder cancer in the NIH-AARP Diet and Health Study". Cancer. 116 (18): 4345–4353. doi:10.1002/cncr.25463. ISSN   1097-0142. PMC   2936663 . PMID   20681011.
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