Troubling Meaty ‘Estrogen’

Women take note. Researchers find that a chemical that forms in overcooked meat, especially charred portions, is a potent mimic of estrogen, the primary female sex hormone. That’s anything but appetizing, since studies have linked a higher lifetime cumulative exposure to estrogen in women with an elevated risk of breast cancer.

Indeed, the new finding offers a “biologically plausible” explanation for why diets rich in red meats might elevate breast-cancer risk, notes Nigel J. Gooderham of Imperial College London.

At the very high temperatures reached during frying and charbroiling, natural constituents of meats can undergo chemical reactions that generate carcinogens known as heterocyclic amines (see Carcinogens in the Diet). Because these compounds all have very long, unwieldy chemical monikers, most scientists refer to them by their abbreviations, such as IQ, MeIQ, MeIQx, and PhIP.

Of the nearly two dozen different heterocyclic amines that can form, PhIP dominates. It sometimes accumulates in amounts 10 to 50 times higher than that of any other member of this toxic chemical family, Gooderham says. Moreover, he adds, although heterocyclic amines normally cause liver tumors in exposed animals, PhIP is different: “It causes breast cancer in female rats, prostate cancer in male rats, and colon cancer in both.” These are the same cancers that in people are associated with eating a lot of cooked meats.

However, the means by which such foods might induce cancer has remained somewhat elusive. So, building on his team’s earlier work, Gooderham decided to probe what the heterocyclic amine did in rat pituitary cells. These cells make prolactin—another female sex hormone—but only when triggered by the presence of estrogen. Prolactin, like estrogen, fuels the growth of many breast cancers.

In their new test-tube study, Gooderham and coauthor Saundra N. Lauber show that upon exposure to PhIP, pituitary cells not only make progesterone, but also secrete it. If these cells do the same thing when they’re part of the body, those secretions would circulate to other organs—including the breast.

But “what was startling,” Gooderham told Science News Online, is that it took just trace quantities of the heterocyclic amine to spur prolactin production. “PhIP was incredibly potent,” he says, able to trigger progesterone production at concentrations comparable to what might be found circulating in the blood of people who had eaten a couple of well-done burgers.

The toxicologist cautions that there’s a big gap between observing an effect in isolated cells growing in a test-tube and showing that the same holds true in people.

However, even if PhIP does operate similarly in people, he says that’s no reason to give up grilled meat. Certain cooking techniques, such as flipping hamburgers frequently, can limit the formation of heterocyclic amines. Moreover, earlier work by the Imperial College team showed that dining on certain members of the mustard family appear to detoxify much of the PhIP that might have inadvertently been consumed as part of a meal.

The human link

Three recent epidemiological studies support concerns about the consumption of grilled meats.

In the first, Harvard Medical School researchers compared the diets of more than 90,000 premenopausal U.S. nurses. Over a 12-year period, 1,021 of the relatively young women developed invasive breast cancers. The more red meat a woman ate, the higher was her risk of developing invasive breast cancer, Eunyoung Cho and her colleagues reported in the Archives of Internal Medicine last November. The increased risk was restricted, however, only to those types of breast cancers that are fueled by estrogen or progesterone.

Overall, women who ate the most red meat—typically 1.5 servings or more per day—faced nearly double the invasive breast-cancer risk of those eating little red meat each week.

Related findings emerged in the April 10 British Journal of Cancer. There, researchers at the University of Leeds reported data from a long-running study of more than 35,000 women in the United Kingdom who ranged in age from roughly 35 to 70. Regardless of the volunteers’ age, Janet E. Cade’s team found, those who consumed the most meat had the highest risk of breast cancer.

Shortly thereafter, Susan E. Steck of the University of South Carolina’s school of public health and her colleagues linked meat consumption yet again with increased cancer risk, but only in the older segment of the women they investigated. By comparing the diets of 1,500 women with breast cancer to those of 1,550 cancerfree women, the scientists showed that postmenopausal women consuming the most grilled, barbecued, and smoked meats faced the highest breast-cancer risk.

These data support accumulating evidence that a penchant for well-done meats can hike a woman’s breast-cancer risk, Steck and her colleagues concluded in the May Epidemiology.

PhIP fighters

Such findings have been percolating out of the epidemiology community for years. Nearly a decade ago, for instance, National Cancer Institute scientists reported finding that women who consistently ate their meat very well done—with a crispy, blackened crust—faced a substantially elevated breast-cancer risk when compared to those who routinely ate rare- or medium-cooked meats.

However, even well-done meats without char can contain heterocyclic amines, chemical analyses by others later showed. The compounds’ presence appears to correlate best with how meat is cooked, not merely with how brown its interior ended up (SN: 11/28/98, p. 341).

At high temperatures, the simple sugar glucose, together with creatinine—a muscle-breakdown product, and additional free amino acids, can all interact within beef, chicken, and other meats to form heterocyclic amines. In contrast, low-temperature cooking or a quick searing may generate none of the carcinogens.

Because there’s no way to tell visually, by taste, or by smell whether PhIP and its toxic kin lace cooked meat, food chemists have been lobbying commercial and home chefs to reduce the heat they use to cook meats—or to turn meats frequently to keep the surfaces closest to the heat source from getting too hot.

The significance of this was driven home to Gooderham several years ago when just such tactics spoiled an experiment he was launching to test whether Brussels sprouts and broccoli could help detoxify PhIP. “I bought 30 kilograms of prime Aberdeen angus lean beef,” he recalls. “Then we ground it up and I gave it to a professional cook to turn into burgers and cook.” Professional cooks tend to move meats around quite a bit, he found. The result: His expensive, chef-prepared meat contained almost no PhIP.

In the end, he says, “I sacked the cook, bought another 30 kilos of meat and prepared the burgers myself. It was a costly lesson.”

Once restarted, however, that study yielded encouraging data.

One way the body detoxifies and sheds toxic chemicals is to link them to what amounts to a sugar molecule. Consumption of certain members of the mustard (Brassica) family, such as broccoli and Brussels sprouts (both members of the B. oleracea species)—can encourage this process. So Gooderham’s team fed 250 grams (roughly half a pound) each of broccoli and Brussels sprouts each day to 20 men for almost 2 weeks. On the 12th day, the men each got a cooked-meat meal containing 4.9 micrograms of PhIP.

Compared to similar trial periods when their diets had been Brassica-free, the volunteers excreted up to 40 percent more PhIP in urine, the researchers reported in Carcinogenesis.

Experimental data suggest that two brews may also help detoxify heterocyclic amines. In test-tube studies, white tea largely prevented DNA damage from the heterocyclic amine IQ (SN: 4/15/00, p. 251), and in mice, extracts of beer tackled MeIQx and Trp-P-2 (see Beer’s Well Done Benefit).

The best strategy of all, most toxicologists say, is to prevent formation of heterocyclic amines in the first place. In addition to frequently turning meat on the grill or fry pan, partially cooking meats in a microwave prior to grilling will limit the toxic chemicals’ formation. So will mixing in a little potato starch to ground beef before grilling (see How Carbs Can Make Burgers Safer) or marinating meats with a heavily sugared oil-and-vinegar sauce (SN: 4/24/99, p. 264).

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