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New Wake Forest Study To Pin Down Soy's Active Ingredient

Scientists at Wake Forest University School of Medicine are beginning a five-year study to determine which ingredients in soybeans are the active ones in protecting against heart disease, stroke, cancer and osteoporosis.

Under a new $2.4 million grant from the National Heart, Lung and Blood Institute, the research team, headed by Thomas B. Clarkson, D.V.M., will focus on two isoflavones (also called phytoestrogens – plant estrogens) in soy: genistein and daidzein.

Clarkson, professor of pathology (comparative medicine), said he is seeking to identify the optimum doses and ratios of genistein to daidzein.

He said, "We have obtained preliminary evidence suggesting that predominantly daidzein rather than predominantly genistein may be of greater cardiovascular benefit."

Genistein is the predominant phytoestrogen in the outer portion of soybeans. Daidzein predominates in the germ of the soybean, he said. (Soy resembles wheat in that respect — most people want whole wheat, but wheat germ also is available, and some prefer that.) The outer portion is 3 to 1 genistein; the germ is 4 to 1 daidzein.

Most studies so far have focused on genistein as the active ingredient in preventing cardiovascular diseases and cancer.

The comparison between different ratios of daidzein and genistein is just one phase of the project which will "explore several unanswered questions concerning the optimal use of soy supplements by both males and females."

Clarkson said he hopes to pin down just how much soy is needed for the optimum preventive dose of phytoestrogen and the optimum therapeutic dose. (The preventive dose is usually much smaller than the therapeutic dose, in which the active ingredients of the food essentially act as a drug.)

And the research team is looking at safety issues as well: how safe is soy for the breasts and uteri of females and what effect, if any, does phytoestrogen have on the reproductive systems of males.

The studies will be conducted in monkeys. Previous work in the monkey colony at Wake Forest has developed evidence that soy phytoestrogens may be a useful alternative to traditional hormone replacement therapy in postmenopausal females, protecting against coronary heart disease and other diseases that ordinarily increase dramatically after menopause.

"Our concentration on postmenopausal females and soy phytoestrogens has increased our awareness of the public health importance of the simultaneous protective effects of soy phytoestrogens on coronary heart disease and hormone dependent cancers," Clarkson said.

The group also has preliminary evidence from a study in young male monkeys that soy may protect against coronary heart disease in males. These studies also indicate that the plant estrogens do not adversely affect the reproductive systems of males.

Clarkson said the developing evidence that soy offers protection against hormone- dependent cancers in females indicates soy "may provide protection against prostate cancer,"

which is also thought to be affected by hormones. So the new study also will focus on adult male monkeys.

A parallel national pilot study in people, headquartered at Wake Forest, also is testing whether soy will reduce the risk of prostate cancer. "In Asian countries like Japan, where soy consumption is high, prostate cancer rates are lower than in Western countries with low soy intake," said Electra D. Paskett, Ph.D., associate professor of public health sciences (epidemiology) and principal investigator. The pilot study of 160 men would evaluate the effect of soy on markers for prostate cancer risk.

Clarkson noted that studies have shown that despite the far lower prostate cancer rates in Japan, "immigrant studies support the hypothesis that environmental factors (the American diet) are critical in prostate cancer development. Japanese who emigrate to the United States quickly assume the cancer incidence rate of U.S.-born men."

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