Ultima Thule

In ancient times the northernmost region of the habitable world - hence, any distant, unknown or mysterious land.

Wednesday, August 02, 2006

You are what you eat -- even if you're a lab rat

By Aussiegirl

Turns out all those studies involving lab rats may have to be thrown on the compost pile. The rodent chow fed to the lab animals may be responsible for skewed results involving research into all sorts of diseases and conditions. Soy is not as healthy as the government would have you believe. Indeed, it is virtually indigestible in its natural form and needs to be heavily fermented as it is in products such as tempeh and tofu in order to be edible. The government has engaged in a wholesale peddling of soy products, touting them as health foods. On the contrary, soy is really not fit to be consumed by man nor beast -- or lab rat, as it turns out.

Dallas Morning News | Latest News

For decades, in thousands of laboratories across the country, biomedical researchers have relied on laboratory rats and mice to devise treatments for cancer, heart disease, inflammation and a host of other human afflictions.

But what if, despite all the rigorous procedures to ensure valuable test results, many of those studies have been skewed by the most seemingly mundane of factors: what the animals are routinely fed?

The concern is that researchers have unwittingly administered hormones present in some rodent chow.

A small but growing number of scientists are warning that these hormones are a hidden element in millions of laboratory experiments – potentially affecting researchers' conclusions on countless aspects of disease.

"Many people don't give a second thought to it," said Leslie Leinwand, a molecular biologist at the University of Colorado in Boulder. "You just buy this stuff in big bags and feed it to mice and rats, and very few people are aware what is in there."

The most commonly used laboratory rodent chows contain soy as a key source of protein. The problem, research has shown, is that soy naturally contains chemicals known as phytoestrogens. These substances can wriggle their way into the lab animals' natural estrogen system, altering their physiology, whether they are male or female.

On Thursday in Durham, N.C., the federal government – which provides about one-third of the funding for biomedical research in the U.S. – will convene a meeting between scientists and rodent feed manufacturers to address the issue. Recommendations that emerge from the meeting will be submitted soon to a peer-reviewed journal.

The implications could be enormous, some scientists warn. Rodent chow containing high levels of phytoestrogens found in soy has been used for more than 70 years, according to chow manufacturers.

"How much of science could we rewrite if we could go back and do experiments on a phytoestrogen-free diet," said Kenneth Setchell, a researcher at Children's Hospital Medical Center in Cincinnati.

Areas of biomedical research most affected by the animal diets remain unclear. But high on the list of concern are studies involving hormones, differences between males and females, and cancer and heart disease.

Not all results will have been influenced by the hormones, scientists say, but researchers can't know which ones unless they check.

"It may be that the vast majority of [disease] models hasn't been affected," Dr. Leinwand said. "The issue is going to be if you take 10 of those models that were tested on soy and put them on another diet, are you going to get different results? And not enough is known yet to say that."

Research that soy contains estrogen-like chemicals appeared as early as 1931. Hundreds of other plants produce them, too. The chemicals can be so powerful that phytoestrogens in clover eaten by grazing sheep can cause fertility problems.

Adding yet another element of uncertainty, phytoestrogen levels in certain chow formulas are now known to vary from batch to batch. Factors as common as weather and geography can affect the level of phytoestrogens in soy plants from crop to crop.

For many chows, "the commercial feeds that are available right now are an absolute nightmare of variability," said Fred vom Saal, a biologist at the University of Missouri-Columbia.

The use of different chow formulas – or even variations in phytoestrogen content between batches of the same chow – could explain why different labs produce different results in similar experiments. And even if phytoestrogen levels are constant from one experiment to the next, researchers should still know they are feeding their animals hormones, scientists say.

Several researchers interviewed were unaware of the power of phytoestrogens to affect experiments.

"That is very typical," Dr. Leinwand said. "I've called people and said, 'What are you feeding your mice?' and they say, 'I have no idea.' "

An informal Dallas Morning News survey of several leading scientific journals found little or no description of the type of chow fed to research animals. Of 50 articles involving rats or mice, only one specified whether the protein source was soy. None mentioned phytoestrogens.

"You can design a wonderful study that will provide good information, but if you use the wrong diet, you may not even find anything," said Julius Thigpen, a microbiologist at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C.

Dr. Thigpen is one of the more widely cited scientists on the issue of these hormone-like chemicals in rodent chow. He said he became aware of the issue when scientists at the institute came to him puzzled that their usually reliable experiments suddenly produced different results.

He suspected that "there may be things in the feed. I found out later it was phytoestrogens."

At first, he said, his warnings that different batches of the same feed formula could vary widely in phytoestrogen levels were ignored. When he submitted his research to present at a scientific meeting, "it was turned down because they didn't think it was important," he said.

Since then, other researchers have had similar revelations. The University of Colorado's Dr. Leinwand said she stumbled on the chow issue when an employee switched a particular breed of mice from a soy-based diet to a milk protein-based diet in preparation for an experiment.

Suddenly, she said, it seemed like there was nothing left to study. The male mice, which ordinarily developed heart disease, were much healthier on the milk protein-based chow. Further studies implicated the soy hormones as part of the reason.

Another scientist said that when he moved his laboratory from Kansas to Tennessee, experiments he had done for years no longer seemed to work. Months of troubleshooting, again, pointed to the soy hormones.

"This is a major problem," said Sudhansu Dey, a biologist at Vanderbilt University Medical Center in Nashville, Tenn. "How can you trust that you can get results that you can repeat?"

Some universities are taking steps to address the problem. After a recent presentation from a feed manufacturer, more researchers at UT Southwestern Medical Center are asking that their mice receive the phytoestrogen-free chow, said veterinarian Gordon Brackee, director of the school's animal resources center.

Re-evaluating the vast amount of animal research will be extremely difficult, and repeating many of those experiments may not be an option, said Dr. Leinwand.

"We can't go back and do 20 years of experiments again," she said.

For now, her lab is doubling the amount of mice it uses so the researchers can test the mice on both soy- and milk protein-based diets. The extra mice and milk-based diet add to the cost of research, she said.

"If we don't see any difference, we'll stick with one diet," she said. "But there have been very few cases where we've not seen any effect."


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