Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones

Author: KD Setchell
Publication: American Journal of Clinical Nutrition, Vol 68, 1333S-1346S

This is a review article about the importance, working mechanism and health benefits of dietary estrogens and isoflavones. Epidemiological and dietary studies have shown the health benefits of dietary estrogens. Soy isoflavones are transformed by the intestinal microflora into compounds, which may reach blood levels high enough to have hormonal and non-hormonal activities. It is now accepted that many diseases are influenced by diet and could be influenced by modification of the diet. Many phytochemicals have been identified which have a biological effect. Lignans and isoflavones are environmental estrogens, which have recently received a lot of attention.

Dietary estrogens and isoflavones have a phenolic ring, which is a prerequisite for binding to estrogen receptors. Dietary estrogens are about 100 to 1000 times less potent than human estrogens (estradiol or estrone).Because isoflavones can bind with estrogen receptors they can act as estrogen agonist or antagonist. One special estrogen receptor is the beta estrogen receptor, which can be found in the tissues of bones, blood vessels, brain and bladder. Isoflavones preferentially bind to these beta estrogen receptors. However, isoflavones have also non-hormonal activity. The isoflavone genistein is an inhibitor of the enzyme protein tyrosine kinase and influences cell proliferation.

Flaxseeds and soybeans are the richest source of dietary estrogens. People in China and Japan eat relatively a lot of soy products and have lower rated of hormone dependant diseases. Soy contains the isoflavones genistein and daidzein in the form of glycosides (which mean they are bound to a sugar molecule). These glycosides are converted into aglycone during digestion by the gut microflora. During the fermentation of some soyfoods (such as miso, shoyu and tempeh), the isoflavones glycosides are also hydrolyzed into aglycones. Our liver conjugates the aglycones again with glucuronic acid or sulphuric acid.

Dietary estrogens have many health promoting properties. Animal studies have shown that soy proteins, containing isoflavones, reduced tumor formation. Administration of genistein to neonatal rats protected the rats during the adult phase against carcinogens. This illustrates that early exposure to isoflavones may give benefits later in life. Breast cancer rates of women in China and Japan, who consume more soy products throughout life, are much lower than compared to Western women. Consumption of soy products increases the length of the menstrual cycle. A longer menstrual cycle is beneficial because it lowers breast cancer risk.
Isoflavones may also lower the risk of prostate cancer. In vitro tests have shown that genistein inhibits the growth of prostate cells. In vivo tests suggest that soy isoflavones may reduce risk of prostate cancer by acting against prostatic dysplasia.

A meta analysis by Anderson J.W. et al showed that soy protein significantly reduce cholesterol levels. The mechanism by which soy protein reduce cholesterol levels is still unclear but isoflavones may play an important role. Isoflavones may reduce plaque formation by inhibiting cell adhesion and changing the activity of growth factors. The antioxidant action of isoflavones may reduce lipid peroxidation and reduce atherosclerosis. Epidemiologic studies show that Japanese and Chinese menopausal women suffer less from menopausal symptoms than Western women do. This could be explained by their higher consumption of soy isoflavones. Studies have shown that soy isoflavones frequency of hot flashes in postmenopausal women. Isoflavones seems also to reduce the risk of osteoporosis with postmenopausal women. Estrogen and isoflavones reduce the activity of osteoclasts, thereby limiting bone resorption.

This study concluded that dietary estrogens have many health benefits. The threshold daily consumption of dietary estrogens to achieve biological activity is around 30 to 50 mg, which can be easily achieved by incorporating modest amounts of soy protein. It is difficult to consume too much isoflavones from natural soy products, but their might be a risk associated with the consumption of dietary estrogens in the form of supplements.