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PHYTOESTROGENS

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What are they?

Phytoestrogens are plant-derived compounds that have estrogenic effects. These compounds are polypenols and act like estrogens in some important ways that produce similar biological responses. The polypenols that have been studied most are - isoflavones such as Genistein, Diadizen, and Biochein - commonly found in soy products. Others that are interesting are coumestrol and lignans such as enterolactone and enterdiol - from the common source of flaxseed. Over 500 plant species contain phytoestrogens, however, the highest concentration is found in red clover, alfalfa, licorice and soybeans.

Why study phytoestrogens?

What has led to research interests in phytoestrogen is evidence from epidemiological studies. In studies of Asian populations with soy intake of 10-50 g/day lower breast and prostate cancer rates have been observed. A prospective study in Australia found breast cancer was three times lower in women with higher urinary phytoestrogen levels than in the normal population of women. Animal studies show that Genistein reduced by 1/2 the mammary tumors in mice and rats. A clinical study with healthy women showed those who consumed soy protein with 42mg of genistein and 27mg of diadizen per day to have these substances in their tissue at protective levels even though enough time had not elapsed to prove a preventive effect on tumor formation.

How does it work?

The most persuasive evidence comes from studies at the cellular level. These have shown that phytoestrogens tend to suppress gene expression in human breast cancer cells, thus interfering with reproduction. Genistein, diadizen, and formononetin (another isoflavoid) affect estrogen sensitive pathways - blocking the routes. Some of the phytochemicals inhibit growth especially of prostate carcinoma perhaps by disrupting the formation of blood supply lines. Genistein and other soy compounds may contain protease inhibitors that keep the cell from a critical stage in its development. All the news is not positive because some phytochemicals have additive antiestrogenic activity in breast cancer cells and can act like an estrogen tumor promoter.

Humans have at least two estrogen receptors. Genistein binds to Beta-estrogen receptors and inhibits 17B-estrodiol thus preventing estrogen promotion for mammary epithelial cells, the most common type and those that develop into the most common form of breast cancer. Another proposed mechanism is on autophospholation - thus blocking the body's estrogen receptors - the slots where it binds in the cell. A biochemical pathway that might be effected is that of tyrosine phosphorlation that is decreased by Genistein. It has been documented that individuals who consume phytoestrogens in their diet, such as from soy protein, have lower levels of the estrogens that the body naturally produces. This is most likely due to the body “seeing” the phytoestrogen as one the body produces and this provides negative feedback so the body produces less naturally so the level stays constant.

Is It Effective?

The popular press have touted estrogen is a protective hormone for many diseases, such as heart disease and post-menopausal osteoporosis. Phytoestrogens have similar effects. The studies seem to show that genistein, the soy phytoestrogen, inhibits prostate cancer cell and breast cancer cell growth. Genistein appears to inhibit the formation of new blood vessels, the process called angiogenesis, which tumors need to grow. In addition, genistein has also been shown to inhibit the activity of several enzymes involved in cell growth and regulation. Moreover based on the epidemiological literature, it has been well documented that the rate of breast, ovarian, endometrial and prostate cancer is lower in populations that have soy products as a staple in their diet.

What is the State of the Science?

Most of the information we observed about the relationship of soy or phytoestrogen consumption to cancer has been from population based studies. Studies have been performed with human cell cultures and on animals, but clinical intervention studies on humans are just beginning. Of concern to some scientists is the potential health risk of consuming large amounts of phytoestrogens in women who have had hormonally dependent cancers such as breast, ovarian or uterine cancer. Too, isoflavones act as alternative substrates for thyroid peroxidase – which theoretically could lead to depletion of iodine and produce hypothyroidism. This is not seen in the Asian studies because the diet is high in iodine-containing foods such as seaweed and sea salt.

Studies are currently progressing to determine the safety and efficacy of super- supplementation. The current recommendation is to eat a diet rich in soy protein of at least 25 grams per day as part of a low saturated fat and cholesterol diet, which may also have cardiovascular and other health benefits. What we do know at this point, is that such a diet could be achieved by eating 40 grams of tofu, or one soy hot dog, a cup of tofu yogurt, or by using 10-15 grams of soy flour in favorite recipes.

Study of the phytoestrogens is a very active area of research at the present time, especially as pertains to isoflavone supplementation in the treatment of osteoporosis which has shown great promise. N-Sights will keep you abreast of breaking news on this topic. Watch further issues for updates.


Helen Lane, Ph.D., R.D., is the Program Director of the Advanced Human Support Technology Lab at the Johnson Space Center.

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