The clamor over soybeans being a superfood has faded. The validity of initial claims over soy isoflavones' promise has not waned. But the hurdle of taking trials to the next stage, humans, is expensive, time-consuming and, in many cases, prohibitive.

A decade ago, scientific studies showed that soy components prevented breast cancer when consumed by prepubescent girls, and there was evidence that it lowered prostate-specific antigen (PSA) levels in animals. The clinical tests on humans necessary to prove these claims will be on a grand scale of both time and expense.

“Soy is still researched to a phenomenal degree, with about 700 studies published each year,” says soy/cancer researcher Mark Messina, adjunct professor in nutrition at Loma Linda University, former National Cancer Institute researcher and expert on the role of soy in diets.

“But like all areas of nutrition, a lot is up in the air,” he says. “Generally, the case in nutrition is that nothing is consistent because people differ so much biochemically, and human studies are so expensive.”

Most potential health benefits accrue to soy genisteins, biologically active soy compounds and plant hormones thought to prevent cancer.

Genistein is thought to work by binding estrogen receptors and partly blocking estrogen's effect. This may help reduce the growth of estrogen-dependent cancers, such as breast and ovarian cancers.

A list of genistein cancer-fighting studies underway is available at http://clinicaltrials.gov/, by searching “soy and cancer.”

“Most of these studies mentioned are large enough to prove genistein's use in cancer treatment,” says Charles Muscoplat, University of Minnesota professor of medicine, food science and nutrition. “But they are not designed to use genistein in normal individuals for prevention; those studies are very difficult.”

The most convincing evidence of genistein's cancer-fighting properties comes from National Cancer Institute research suggesting that eating soyfoods may halve the rate of breast cancer of women who eat it before or during puberty. “In this study, Asian women in California who consumed higher amounts of soy between the ages of five and 11 were 58% less likely to develop breast cancer, as compared to women who consumed less soy during this period of their lives,” Messina says.

“These exciting results are similar to those from a Chinese study, which found that girls with high soy intake between the ages of 13 and 15 were half as likely to develop breast cancer later in life,” Messina adds. “The amount of soy consumed as adults was not protective against breast cancer, although soyfoods' overall benefits in reducing cholesterol and providing high-quality protein are well proven.”

Two other human studies, one from Canada and another from California, support the benefit of eating soyfoods during childhood and adolescence. In addition,animal studies suggest that the phytoestrogens (plant-derived estrogens) in soyfoods change the cells in the developing breast, protecting them permanently from becoming cancerous.

“We have consistent data between animal studies and epidemiological studies that consuming as little as one or two servings of soy products a day by 10-year-olds provides this valuable benefit,” Messina concludes.

“To prove this conclusively, we would need a study of 10,000 humans spanning 50 years. In the meantime, there is huge upside potential to prevent breast cancer and no potential downside. If we find out 40 years from now that it is protective, we would have lost this opportunity,” he says.

In test tubes, high amounts of (soy) genistein have inhibited cancer growth. But reproducing those results in humans, and duplicating high concentrations of genistein in humans, or in animals, has not been done.

Soy may bind testosterone in a similar fashion, suggesting a potential role fighting prostate cancer, according to research by University of Minnesota cancer researcher Mindy Kurzer.

Of eight studies examining the effects of soy in reducing PSA blood levels, half suggested a benefit and half did not. “If I were a prostate cancer patient, I would consume soyfoods; there seems to be something there,” Messina says. “A recent unpublished study found that of 13 men who did not receive soyfoods, six developed cancer. Of those who did receive soy,only one developed cancer.”

In laboratories, genistein has been found to slow angiogenesis and inhibit tyrosine kinase enzymes, which are directly involved in cancer cell growth and regulation.

“Genistein's anti-tumor effects in the laboratory are similar to very strong drugs,” says Muscoplat. “Genistein is both preventing and treating cancer, being used in cancer patients in conjunction with current cancer therapy with very optimistic results,” says Muscoplat. “In this manner, it will someday be used as a drug, not a food.”

He's so convinced of their health benefits that he eats a handful of soy nuts or soy products twice a day.

“We'll see soybeans bred for their genistein content, and used to fight cancer and heart disease,” Muscoplat says. “You will see agriculture become a full partner in human health and disease prevention. I promise it will happen.”

Genisteins modify genetic expression beyond simply providing nutrients, he says. To better understand genetic expression, consider butterflies. They are genetic twins to caterpillars, but their genes are expressed differently, accounting for the differences in their form. The genetic expression of their wings and legs is turned on or off, Muscoplat says, much like the way that genes express some cancers can be modified by eating soybeans.

Soy genistein has reduced the incidence of pancreatic cancer in mice, according to research by Ramzi Mohammad, Wayne State University School of Medicine,Detroit. He recommends clinical trials using genistein combined with chemotherapy to treat non-Hodgkin's lymphoma.

The challenge is that what works in lab mice has yet to be proven in humans, says Messina.

“Genistein is likely to be very good,” Muscoplat says, “but no big company will make it a drug because it will be hard to get patent protection.”