March 23, 2014

Marinades Reduce Heterocyclic Amines from Primitive Food Preparation Techniques

A review of research on heterocyclic amine (HCA) formation in meat during barbecuing and cooking, with a focus on data related to recipe and menu development to lower carcinogen production or mitigate mutagenic effects.
It is certainly possible, as these papers suggest, to significantly lower the formation of carcinogens during cooking, even while barbecuing. Incorporating specific ingredients into meat through mixing, marinades, or rubs provides accessible means to inhibit formation of HCAs.


A review of research on heterocyclic amine (HCA) formation in meat during barbecuing and cooking, with a focus on data related to recipe and menu development to lower carcinogen production or mitigate mutagenic effects. HCA formation may be reduced by decreasing cooking temperature, cooking time, or manner of cooking. The addition of vitamin E, garlic, rosemary, fruit pulp, and other seasonings and spices may lower HCA production. These ingredients may be incorporated through direct mixing, marinades, or rubs and often inhibit HCA formation by as much as 70%. Certain foods (e.g., yogurt, beer) lower mutagenic action of HCAs. Altering cooking methods by incorporating these concepts may play a significant role in reducing risk of cancer.


In North America and elsewhere in the world, summer months bring an upsurge in barbecuing. Animal-sourced foods, typically the muscle flesh from poultry, bovine, or porcine species, undergo reactions during cooking that produce a series of chemicals referred to as heterocyclic amines (HCAs). These chemicals form through the condensation of creatine/creatinine and the Strecker degradation radicals that are generated during the Maillard reaction. These same reactions are responsible for the generation of other chemicals that provide barbecue’s hallmark flavor. Higher heat favors greater HCA production.


Modern methods of barbecuing, using metal cookware, indirect heat, conduction, and transfer of heat via water, steam, and microwave energy produce notably lower amounts of HCAs because they do not heat the meat surface to as high a temperature.

Heterocyclic amines are mutagenic and are classified as carcinogens. Numerous epidemiologic studies have linked high intake of meat with increased risk for a variety of cancers including breast, colorectal, and prostate cancers.1,2,3 It is now well accepted that high exposure to meat carcinogens, particularly HCAs, may increase the risk of human cancer.

Heterocyclic amine production during cooking is determined by 4 factors:

Type of food. Only muscle meats form HCAs. Other animal-sourced foods (e.g., milk, eggs) do not produce significant quantities of HCAs.

Level of heat. Temperature is the most significant determinant; the higher the temperature, the more HCAs produced. Thus the following two factors are important in that they affect the final temperature.

Cooking method. The higher the heat, the worse the problem; barbecuing, broiling, and frying produce the most HCAs.

Cooking time. Longer cooking time increases HCA production.

There are 17 identified groups of HCAs. The most notable are 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) and 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx). In this review, no attempt will be made to differentiate or distinguish between these subtypes.

Rare vs. Well-Done

Frequent consumption of well-done meat has been correlated with risk for adenocarcinoma of the stomach. Even when the data from those who barbecue or grill their meat frequently were excluded, individuals who prefer their meat cooked well-done have an odds ratio for stomach adneocarcinoma over triple that of those who consume similar quantities of meat but prefer it rare or medium rare.4,5

Well-done meat contains more HCAs than rare meat.6 Broiling creates more HCAs than baking. Pan-frying produces fewer HCAs than charcoal grilling.7 Barbecuing, because it exposes meats to the highest temperatures, produces the most HCAs of any cooking method. Yet despite the science to support eating more rare meats, popular preference has shifted in the opposite direction. Concern about foodborne illness has led some jurisdictions to actually ban the serving of rare or medium-rare cooked meats in restaurants. Public perception of this “safety issue” has followed suit. Is the short-term benefit achieved by these sales restrictions in reducing gastrointestinal illness outweighed by a long-term increase in cancer?

Changing Habits

Even small modifications in cooking methodology affect HCA production. For example, when ground beef patties are pan-fried, even the frequency with which they are flipped significantly changes HCA production. Frequent flipping prevents the meat from reaching as high a temperature, thereby reducing the HCAs formed.8 Oven temperature makes a significant difference. The National Cancer Institute reports “a threefold increase in the content of HCAs when the cooking temperature was increased from … 392° to 482°F” in oven-baked beef.9

Although the information that barbecued meat increases cancer rates is both adequately documented and well understood, there has been little if any impact in the consumption of barbecued meats, and certainly none to discourage consumption of overcooked meats.
If anything, barbecue cooking is growing in popularity. The television show Barbecue University, which claims to be “the hottest cooking show on TV” is an example of this interest. The month of May was declared National Barbecue Month by the Hearth, Patio & Barbecue Association (HPBA). The term heterocyclic amine does not appear on the Web sites of the HPBA, the National Barbecue Association, the California Barbecue Association, or the South Carolina Barbecue Association.

As primitive cooking methodologies are too firmly entrenched in popular culture to remove, other approaches have been investigated that show promise at lowering the contribution that HCAs from barbequing add to the public’s cancer risk.

These approaches fall into three categories:

•Reduce HCA production by cooking at lower temperatures and or for less time.

•Chemically inhibit HCA formation during cooking.

•Neutralize HCA mutagenicity.

Reducing HCA Formation by Adding Other Foods

A number of chemicals, many of them polyphenols of plant origin, have been shown to interfere with the formation of HCAs during cooking. Many of these plants are edible and impart desirable sensory characteristics to the meat, and thus are found acceptable by consumers.

There are 3 readily accessible techniques for incorporating these chemicals into the meat.

Mixing. These chemicals can be mixed directly into ground meat, or they can be incorporated during the grinding process.

Marinating. Presoaking the meat in dissolved solutions of suspensions effectively incorporates the marinade into the muscle fibers.

Rubs. Topical application of protective chemicals is reasonably effective.

The following foods, when used as marinades or mixed into meat, can reduce the production of HCAs during high-temperature cooking.

Fruits. A number of different foods added to beef patties and sausages act as antioxidants and lower HCA production during cooking. Cherries are probably the most well-known of these additions.10 Cherries keep meat fresh longer, preventing lipid degradation during storage, and result in a finished cooked product with higher moisture content while also markedly reducing HCA production. Dried plums and apples are also used in this way for similar effect.11 Garlic added directly to hamburger patties also lowers HCA production—in one study by more than 60%.12

Virgin olive oil. In a 2003 paper, Swedish researchers reported that they fried beef patties in six different types of oil and measured the amount of HCAs produced. Fewer HCAs were formed in the burgers cooked in virgin olive oil than in any other oil tested.13 Thus marinades or rubs that utilize virgin olive oil are expected to reduce HCA formation during cooking.

Sauces, but not traditional barbecue sauce. Research has been done on marinades that reduce HCA production in both beef and chicken. Chicken, with skin intact, produces far higher amounts of HCAs than beef. Neruraker et al, in their 1999 paper, compared the HCA “content of beef steaks marinated overnight with teriyaki sauce, turmeric-garlic sauce, or commercial honey barbecue sauce with that of unmarinated steaks.” After 15 minutes of cooking, the meat treated with teriyaki marinade had a 60% lower HCA level than the unmarinated meat. The turmeric-garlic marinade had a similar effect. In contrast, a standard barbecue sauce containing tomato solids and sugar caused a significant increase in chemical formation, doubling and even tripling levels after 15 minutes of cooking.14 Some attribute this action to the added fructose in the product utilized.

Garlic, onions, and lemon juice. In a 2007 paper, Gibis reported on experiments investigating varying amounts of garlic, onion, and lemon juice in a marinade that was used prior to cooking ground beef patties. Varying the amounts of these ingredients produced differing reductions in HCA formation. Garlic at 20 gm/100 gm marinade reduced carcinogen production by about 70%. The author determined that “the optimum amounts of onion, garlic, and lemon juice [are] 31.2%, 28.6%, and 14.6% [respectively] in marinade.”15 This suggests ideal marinade recipes should contain one part lemon juice and two parts each of onion and garlic.

Beer and wine. A number of studies have investigated beer and wine as marinades for beef. A 2008 paper that tested both beer and wine marinades on steaks before pan-frying reported that, although both were effective at reducing production of certain specific types of HCAs, beer accounted for a greater decrease in production.16

Vitamin E and rosemary. Chemicals known for their antioxidant effect, in particular vitamin E and the herb rosemary, are effective at lowering HCA production. Vitamin E at two concentrations (1% and 10% based on fat content), added directly to ground beef, reduced HCA production by 70%. A comparable inhibition of HCA formation was achieved by adding vitamin E (1% based on fat content) to the patty surfaces before frying. Various rosemary extracts, both water- and alcohol-based, even at concentrations as low as 0.05%, have been shown to be even more effective, inhibiting HCA formation by more than 90%.17,18

However, a recent Egyptian study found that rosemary actually increased HCA production in beef shawerma. The same paper reports that in other foods such as grilled chicken and fried liver, rosemary extracts inhibited HCA in a manner as predicted by other published research.19

Other additives. Several other, less common ingredients should be considered as meat additives. A Chinese study that compared the inhibitory effect on HCA production of extracts of apple, elderberry, grape seed, and pineapple, found that “apple and grape seed extracts were … the most effective in both the degree of inhibition in the formation of individual HCAs … and in the reduction of total HCA content (approximately 70% relative to the control).20

The Asian medicinal herb fingerroot (Kaempferia pandurata), a relative of ginger and galangal, is utilized in some Thai recipes. This root lowers HCA production specifically through “inhibition of the first step of enzymatic activation of heterocyclic amines.”21

HCA Reduction in Poultry

Simply removing the skin from chicken before cooking reduces HCA production significantly.22 The Lawrence Livermore Laboratories shared a recipe for a marinade for chicken breast in a 1997 paper. They found that a “mixture of brown sugar, olive oil, cider vinegar, garlic, mustard, lemon juice and salt … reduced the total detectable heterocyclic amines from 56 to 1.7 ng/g, from 158 to 10 ng/g and from 330 to 44 ng/g for grilling times of 20, 30 and 40 min, respectively.”23

Perhaps this marinade would have proved more effective with the addition of a small quantity of red wine. A 2006 paper testing a red wine marinade on HCA formation in fried chicken breasts reported a reduction in one particular HCA by 88%.24

Even with pretreatment with marinades, cooking temperature has a primary effect; lowering cooking temperature produces less HCA and lower mutagenic activity, without lowering the “sensory quality of the products.”25

Neutralizing HCAs

Another approach to lowering carcinogenicity of HCAs formed during cooking is to inactivate them before they can cause mutagenic damage. Genotoxic in vitro testing tells us that green tea, black tea, rooibos tea, red wine, blueberries, blackberries, red grapes, kiwi, watermelon, parsley, and spinach all inhibit the mutagenic activity of certain HCAs.26 The chemical sulforphane present in cruciferous vegetables has also been shown to have antimutagenic effects against HCAs.27 The bacteria found in fermented dairy foods also have a neutralizing effect.28,29

The yeast in beer appears to have a similar neutralizing effect. Consuming beer in close proximity in time to when barbecued meat is eaten is one of the most effective ways to lower HCA mutagenicity. Dark or stout beers are in some reports more effective than paler beers.30,31,32 Green tea extracts also lower HCA mutatgenic potential.33 Thus incorporating any of these foods into meals containing barbecued meat or poultry may lessen the mutagenic effect.


It is certainly possible, as these papers suggest, to significantly lower the formation of carcinogens during cooking, even while barbecuing. Incorporating specific ingredients into meat through mixing, marinades, or rubs provides accessible means to inhibit formation of HCAs. Increasing public awareness of these issues may well spur manufacturers to develop products specifically developed to reduce carcinogen formation during food cooking. Instilling a few simple cooking habits in our patient populations may significantly change their cancer risks.

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