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Feeling the heat: are overcooked meat and poultry dangerous?

Who wants the last piece of blackened chicken off the barbecue? Not research chemist Mark Knize.

"I'm much more willing than my parents, who were raised during the Depression, to throw away a piece of meat that's been on the grill too long," notes Knize, who recently retired from the Lawrence Livermore National Laboratory in Livermore, California.

Why? "There's something produced in overcooked meat that causes mutations to DNA, and it may be related to cancer in people."

Heterocyclic amines--HCAs for short--are created in meat, poultry, and fish that are cooked at high temperatures. They cause cancer in animals, and there's some evidence that they do the same in humans. But so far, there's no smoking gun.

Part of the problem is that HCAs are tough to study. For one thing, investigators have to rely on people who report how much of what they eat, and one person's "well-done" meat, chicken, or fish could easily be another's "medium" or "very-well-done." And it may turn out that HCAs don't have much impact on the risk of cancer.

While researchers sort it all out, it makes sense to try to cut your exposure. It's not hard to do.

Mutagens in Meat

In the 1970s, researchers discovered that something in fried beef was mutagenic. (Mutagens bind to DNA and can set off a chain of events that culminates in cancer.) At first, scientists thought that the culprit was the herbicides in cattle feed.

"It was hard to believe that anything natural could be a pure mutagen," says Lawrence Livermore's Mark Knize. "But after we figured out the structure of these compounds, it was pretty obvious that it could come from natural substances in meat."

Lawrence Livermore researchers discovered that heterocyclic amines (HCAs) form when amino acids combine with creatine or creatinine as they're heated together to a high temperature. (Amino acids are the building blocks of protein, creatine helps supply energy to muscle and nerve cells, and creatinine forms when creatine breaks down.)

"As soon as you get over 350[degrees], HCAs show up," says Lawrence Livermore's Jim Felton, who has been studying the compounds for two decades. Researchers have found about 20 HCAs in cooked meat. The most common one in the American diet is PhIP (pronounced "fip").

And PhIP is a carcinogen, at least in animals. Feeding large doses of PhIP to rats causes colon, breast, and prostate tumors. And that caught researchers' attention, says Knize, "because there are very few chemicals that cause colon and breast cancer in animals."

What about in people? PhIP and three other HCAs are each "reasonably anticipated to be a human carcinogen," according to the authoritative International Agency for Research on Cancer.

Not So Hot

Lawrence Livermore investigators have found that the higher the temperature meat reaches--and the drier it gets--the more HCAs are produced. For example, hamburgers cooked very-well-done have eight times more PhIP--and those cooked extra-well-done have 12 times more PhIP--than hamburgers cooked to medium.

That might explain why fast-food burgers--which are cooked quickly--have fewer HCAs than burgers prepared at home. "They're not exposed to the high heat over a long time," says Knize. "There are some HCAs, but not what you get off the backyard barbecue."

Cooked poultry also produces PhIP, but many people don't cook it long enough to dry it out, notes Knize. "I wouldn't necessarily say it's better or worse than beef."

Fish, on the other hand, is generally clean. "The way we cook fish in the United States creates low levels of HCAs," says Knize. "We don't seem to cook it that dried out, and it's the more drying conditions that make the HCAs." Even Cajun-style blackened fish is okay, he adds. "It seems to be the sauce and the sugars that blacken, not the fish."

DNA in a Bind

Do the HCAs in overcooked meat and poultry cause cancer in people?

"It seems like a simple question to ask, but it's quite a challenge," says Knize. Since it's unethical to feed HCAs to people to see if they get cancer, scientists are loft with trying to link what people say they typically eat to whether or not they are diagnosed with cancer over the next five years or more.

That's dicey with any food. It's even tougher when researchers have to try to figure out how much HCAs someone got from their meat or poultry.

"We can't say you ate a steak, so therefore you got such-and-such an amount of HCAs," Knize notes. "It's really how the meat was cooked and how well-done it is that matter. So it's complicated."

That's why researchers at the National Cancer Institute have created a questionnaire that asks study participants how their food was cooked, and that uses photos to help them identify meat and poultry that is rare, medium, well-done, or very-well-done.

Some studies are beginning to use the questionnaire, says NCI senior investigator Rashmi Sinha, who led the team that created it. But any questionnaire "is subject to a fair bit of imprecision," notes epidemiologist Andrew Flood of the University of Minnesota.

Despite those difficulties, evidence is building that well-done meat may increase the risk of several kinds of cancer.

Prostate Cancer

Two prospective studies--the kind that record what people say they eat and then follow them for years to see who gets sick and who doesn't--have linked the consumption of well-done meat and poultry with an increased risk of prostate cancer:

* In a study of 23,000 U.S. agricultural workers published earlier this year, National Cancer Institute researchers found that men who ate the most well-done or very-well-done meat and poultry (about 20 ounces a week) were twice as likely to be diagnosed with advanced prostate cancer as men who ate the least (about 4 ounces a week). (1)

* In a study of 29,000 U.S. men, those who ate the most very-well-done meat and poultry--at least 2 1/2 ounces a week--were 70 percent more likely to be diagnosed with prostate cancer than those who ate none. (2) (The study didn't look at well-done.)

A preference for well-done meat might be one reason why African-American men have the highest rates of prostate cancer in the world. Black American men consume two to three times more PhIP than white American men, say Lawrence Livermore scientists.

"A light went on," says researcher Garrett Keating. "We thought maybe this would explain their high rates of prostate cancer."

Since 2001, Keating and his colleagues at Lawrence Livermore have been monitoring about 400 African-American men in their 50s, 60s, and 70s in Oakland, California. Those who consume the most PhIP from their food are 32 times more likely to have very high PSA levels (20 or more) than those who eat the least. (PSA is a measure of prostate-specific antigen in the blood. A PSA above 4 signals possible prostate cancer.)

"Part of it may be higher levels of PhIP exposure," notes prostate cancer epidemiologist Benjamin Rybicki of the Henry Ford Hospital in Detroit. "But African-Americans also metabolize PhIP differently from Caucasians, and that might also put them at higher risk."


Rybicki and scientists at Columbia University in New York have studied prostate tissue from black and white American men who have prostate cancer. They found higher average levels of PhIP bound to DNA--a likely step on the road to cancer--in those who ate more grilled red meat, especially hamburger, than in those who ate less. (3) Men who ate grilled chicken or fish didn't show more PhIP bound to DNA.

"Recent studies show clearly that PhIP definitely leads to tumor formation in the prostates of laboratory rats," says Rybicki. "Data from human studies are still equivocal," he notes, "because it's harder to study the effects of exposure in humans than it is in animals." Still, "I think that human studies may eventually implicate PhIP as a prostate carcinogen."

Pancreatic Cancer

In the mid-1990s, 332,000 members of AARP completed a detailed National Cancer Institute questionnaire that asked, among other things, about how they cooked their meat and poultry. Over the next five years, men who reported eating the most grilled or barbecued red meat were about 50 percent more likely to be diagnosed with pancreatic cancer than men who reported eating the least. (4)

"There haven't been enough epidemiologic studies to definitively say that meat cooked at high temperature is associated with pancreatic cancer," says NCI epidemiologist Rachael Stolzenberg-Solomon. "But a 50 percent increased risk is right in the ballpark with another established risk factor for pancreatic cancer--being overweight."

The AARP study didn't see an increased risk in women who ate red meat cooked at high temperature. "Men ate more red meat than women, so maybe the women weren't eating enough to reach the threshold necessary to see an association," Stolzenberg-Solomon speculates.

Colorectal Cancer

HCAs cause colon cancer in laboratory animals. And there is abundant epidemiological evidence--from studies that look at what large groups of people eat and what diseases they get--that eating red meat (no matter how it's cooked) is linked to a higher risk of colorectal cancer in people.

"But not all of the harmful effect of red meat can be explained by HCAs," says National Cancer Institute researcher Rashmi Sinha. For example, the nitrites in processed meats and the iron in all red meats may also play a role.

Researchers have used Sinha's detailed questionnaire on meat-eating habits in studies that track healthy people to see if those who eat more HCAs have a higher risk of colorectal cancer, but no results have yet been published.

"That's the problem with prospective studies and cancer," notes Sinha. "We have to wait a while for the answers."

Scientists haw, looked at cooked meat and precancerous colon polyps called adenomas, though. When University of Arizona researchers studied 869 men and women who had had at least one adenoma removed, they found that those who ate the most well-done or very-well-done meat were about 70 percent more likely than those who ate the least to have advanced or multiple lesions return. (5)

"It's thought that 90 percent of colorectal cancers arise from adenomas," says Amanda Cross, a colleague of Sinha's at NCI. "So if we see an association with adenomas, it's likely to hold for cancer as well."

Breast Cancer

"There's very strong laboratory data from cell lines and animal models that HCAs are mammary mutagens," says Christine Ambrosone, chair of the department of cancer prevention and control at the Roswell Park Cancer Institute in Buffalo, New York. (Cell lines are cells that have been extracted from living tissue and grown in labs.)

"But if you look at the whole body of evidence, it really hasn't been established that these substances increase the risk of breast cancer in humans."

For example, in a new study of more than 11,000 Swedish women aged 50 and older, those who consumed the most HCAs were no more likely to be diagnosed with breast cancer over a 10-year span than those who ate the least. (6)

And in the United States, among nearly 33,000 women in the Nurses' Health Study, those who ate "charred" meat one or more times a week were no more likely to be diagnosed with breast cancer over a five-year period than those who never ate charred meat. (7)

"It has been difficult to nail down the effect of HCAs in large studies of women," says Ambrosone.

She points out that it's hard to put a number on exactly how much HCAs people are getting from cooked meat, even with a questionnaire that has photos of meat cooked to different temperatures. "It's still difficult to assess how much they're getting."

Then there's genetic variability. Some people have enzymes that activate HCAs into mutagens more quickly than other people, Ambrosone notes. That means the same amount of HCAs may cause more damage in people who are rapid activators than in people who are slow activators.

The Bottom Line

"These cancer-causing chemicals are in meat and poultry, so it is definitely plausible that they cause cancer in people," says Mark Knize. "But there certainly isn't proof yet."

The National Cancer Institute's Rashmi Sinha agrees. "I think there's probably something going on, but it's not completely clear for each of the cancer sites."

Until researchers get a better read on whether HCAs in meat and poultry increase the risk of cancer, it makes sense to try to limit them (see "How to Cut the HCAs").

How to Cut the HCAs

"It's better not to eat burned or highly browned meat," says National Cancer Institute researcher Rashmi Sinha. Here are some tips from HCA researchers at the Lawrence Livermore National Laboratory, which is a research institute run by the U.S. Department of Energy:

* Marinate. "If you marinate before cooking, you can reduce the amount of HCAs," says chemist Mark Knize. For example, marinating chicken for 40 minutes (in a mixture of brown sugar, olive oil, cider vinegar, garlic, mustard, lemon juice, and salt) cut HCAs by more than 90 percent. "There's no magic ingredient," says Knize. "It just seems like a goopy marinade prevents drying reactions right at the surface."

"We believe the marinade is cooling the meat and protecting it from a high temperature," adds researcher Jim Felton. And it doesn't matter how long the meat sits in the liquid. "You get the same result whether you marinate for 24 hours or dip the food right before cooking," notes Felton.

* Microwave first. "You'll eliminate about 90 percent of the HCAs that could form in cooked chicken or ground meat if you first microwave it for 1 1/2 to 2 minutes and then throw out the juices that are released," says Knize. Out in the liquid go some of the meat's or poultry's creatinine, creatine, and amino acids, all of which can form HCAs.

* Try seafood. As long as you don't char your seafood, it will have fewer HCAs than red meat or poultry. (Most blackened fish in restaurants isn't really charred. It's the sauce that blackens, not the fish.)

* Keep it moist, Hot dogs and sausages have fewer HCAs than other meat, says Knize. "It's hard to know exactly what's happening," he notes, "but the casing somehow protects the meat. It may keep the meat much moister and prevent the drying conditions that lead to HCAs." Does it help to cook poultry with the skin on and remove it before eating? "That would remove some HCAs," says Knize. "But a better solution is not to cook it so well-done and to such drying conditions."

* Bake, roast, or stir-fry. Grilling and barbecuing generate the most heat, so they produce the most HCAs. Next come pan-frying and broiling. Instead, try baking, roasting, or stir-frying. And, if you pan-fry, "we recommend lowering the temperature on the stove as the best way to reduce the amount of HCAs," says Knize. Cutting the frying temperature of ground beef from 480[degrees] to 390[degrees], for example, eliminates around 80 percent of the HCAs.

* Cook in liquid. Cooking with liquid--boiling, steaming, poaching, or stewing, for example--generates no HCAs because the temperature of the meat never tops the boiling point of water. Cooking in oil is another way to eliminate HCAs (though it does add calories). "lf you deep-fry, you don't get any of these compounds because the temperature never gets high enough," says Felton.

* Flip frequently. Reducing the surface temperature of meat or poultry means fewer HCAs. Cooking meat for six minutes per side instead of 10 minutes, for example, cuts the HCAs by 70 percent. "And we've found that if you flip every minute," says Knize, "you just don't form HCAs."

* If the meat or poultry is well-done, skip the pan drippings. The drippings can have more HCAs than the meat or poultry itself, says Knize.

* Eat your veggies. Veggie burgers and cooked vegetables generate little or no HCAs. In fact, cruciferous vegetables, like broccoli and Brussels sprouts, contain compounds that rev up enzymes in the liver that detoxify HCAs. Researchers have found that men who were fed a total of about three cups of cooked broccoli and Brussels sprouts every day for 12 days before eating well-done meat increased the rate at which their bodies removed HCAs by 20 to 30 percent. (1)

(1) Carcinogenesis 25: 1659, 2004.

(1) Cancer Epidemiol Biomarkers Prev. 17: 80, 2008.

(2) Cancer Res. 65:11779, 2095.

(3) Cancer Epidemiol. Biomarkers Prev. 16: 803, 2007.

(4) Cancer Epidemiol. Biomarkers Prev. 16: 2664, 2007.

(5) Carcinogenesis 28: 2019, 2007.

(6) Int. J. Cancer 123: 1637, 2008.

(7) Int. J. Cancer 80: 13, 1999.
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Title Annotation:SPECIAL FEATURE
Author:Schardt, David
Publication:Nutrition Action Healthletter
Article Type:Clinical report
Geographic Code:1USA
Date:Sep 1, 2008
Previous Article:Iron & cancer.
Next Article:Corn off the cob.

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