Soy estrogens: Too much of a good thing?

Estrogen has a mixed reputation. It wards off heart disease and sustains bone mass in women, but it appears to promote breast and ovarian cancers. Two studies using female mice now suggest that a form of estrogen found in soybeans and generally considered a safe dietary supplement also could contribute to the risk of cancer.

The chemical analogs of estrogen found in soybeans and other plants belong to the class of chemicals called isoflavones and appear to share some of the hormone's beneficial qualities. In contrast to estrogen, the research on soy isoflavones has been overwhelmingly positive. This has led to the marketing of capsules of genistein, the primary isoflavone in soy.

In a study that will appear in an upcoming issue of NUTRITION AND CANCER, researchers attempted to induce breast cancer in mice by dosing 19 animals, starting at 7 weeks of age, with chemicals known to cause breast tumors. Then they fed food pellets highly fortified with genistein to 11 of the mice and gave the other 8 animals genistein-free pellets.

Five of the 11 mice getting genistein developed tumors around age 34 weeks, whereas none of the 8 mice in the control group did, says study coauthor J. Kevin Day of the University of Missouri in Columbia.

In the other study, which appears in the June 1 CANCER RESEARCH, researchers injected newborn mice for 5 days with genistein dissolved in corn oil. Other mice received comparable doses of diethylstilbestrol (DES), a synthetic estrogen known to cause cancer. A third group received injections of corn oil only. At 18 months of age, 6 of 17 genistein-treated mice and 4 of 13 DES-treated mice had developed uterine cancer, but none of 13 control mice had.

The proportional amount of genistein in this study is slightly higher than that received by infants consuming soy formula, says coauthor Retha R. Newbold, of the National Institute of Environmental Health Sciences (NIEHS) in Research Triangle Park, N.C. These mice received 50 milligrams per kilogram of body weight per day. A baby gets about 27 mg/kg per day, says Newbold.

"I don't want to overly worry parents" using soy formula, says Newbold. "We have always been careful when extrapolating from mice to humans. But I definitely think there is cause for concern."

Most studies showing benefits from soy have focused on adult animals and people. The NIEHS study suggests that newborns' exposure to soy deserves more investigation, Newbold says.

Both studies run counter to research indicating that foods high in soy protect against cancer. Mice in the new studies received high doses of genistein but not of other isoflavones and proteins found in whole soy. That could account for the lack of an anticancer effect from genistein in the studies, Day says.

Despite these reports, soy has staunch defenders. "This work is interesting academically, [but] the neonatal mouse is not a neonatal human," says Kenneth D. R. Setchell of the University of Cincinnati. He questions any conclusions about babies' health drawn from the NIEHS study. Millions of infants have consumed soy formula since the mid-1960s. Had cancer risk increased for those people, he says, "we should have seen many hundreds of cases reported in the [scientific] literature."

Indeed, pro-soy data continue to roll in. A study in the May CANCER EPIDEMIOLOGY, BIOMARKERS & PREVENTION finds that higher intake of soy foods--such as tofu--among Chinese girls during adolescence correlates with less breast cancer in middle age. Many scientists attribute low cancer rates in Asian countries in part to soy-rich diets.

Day acknowledges that soy is generally a healthful food. "I tell my friends to eat whole soy--and fruits and veggies," he says. "But when you start popping pills with high concentrations of genistein, our model suggests, you might run into problems."