Phytoestrogens

Phytoestrogens sometimes called "dietary estrogens" are a diverse group of naturally occuring non steroidal plant compounds that because of their structural similarity with estradiol (17β-estradiol), have the ability to cause estrogenic or/and antiestrogenic effects. Their name comes from phyto = plant and estrogen = estrus (period of fertility for female mammals) + gen = to generate.

The similarities, at molecular level, of estrogens and phytoestrogens, allows these to mildly mimic and sometimes act as antagonist to estrogen. Phytoestrogens were first observed in 1926 but it was unknown if they could have any effect in human or animal metabolism. In the 1940s it was noticed by first time that red clover (a phyoestrogens-rich plant) pastures had effects on the fertility of grazing sheeps. Researchers are still exploring the nutritional role of these substances in such diverse metabolic functions as the regulation of cholesterol, and the maintaining of proper bone density post-menopause. Evidence is accruing that phytoestrogens may have protective action against diverse health disorders as prostate, breast, bowel, and other cancers, cardiovascular disease, brain function disorders, menopausal symptoms and osteoporosis

The key structural elements crucial for the estradiol-like effects are :
 * The phenolic ring that is indispensable for binding to estrogen receptors (ERs)
 * The ring of isoflavones mimicking a ring of estrogens at the receptors binding site
 * Low molecular weight similar to estrogens (MW=272)
 * Distance between two hydroxyl groups at the isoflavones nucleus similar to the occurring in estradiol
 * Optimal hydroxylation pattern

In addition to interaction with ERs, phytoestrogens may also modulate the concentration of endogenous estrogens by binding or inactivating some enzymes and may effect the bioavailability of sex hormones by binding or stimulating the synthesis of sex hormone binding globuline (SHBG).

Phytoestrogens mainly belong to a large group of substituted phenolic compounds known as flavonoids: the coumestans, prenylated flavonoids and isoflavones are three of the most active in estrogenic effects in this class. The best-researched are isoflavones, which are commonly found in soy and red clover. Lignans have also been identified as phytoestrogens, although are not flavonoids. Mycoestrogens (mycotoxins) have similar structures and effects, but are not components of plants, these are mold metabolites of Fusarium, a fungi that is frequently found in pastures as well as in alfalfa and clover. Although mycoestrogens are rarely taken into account in discussions about phytoestrogens, these are the compounds that initially generated the interest on the topic.

Phytoestrogens cannot be considered as nutrients given that the lack of these in diet doesn't produce any characteristic deficiency syndrome nor they participate in any essential biological function. A COT draft report from the UK Food Standards Agency presents an update of methods for a more accurate analysis of phytoestrogen content in plants and food, concluding that research in recent years is more reliable than previous studies.

Ecology
These compounds in plants are an important part of their defense system mainly against fungi.

Phytoestrogens are considered archiestrogens (ancient, naturally occuring) and as dietary phytochemicals they are considered as co-evolutive with mammals. In human diet, phytoestrogens are not the only source of exogenous estrogens nor are they considered the largest source. Xenoestrogens (novel, man-made), which are found as food preservants and ingredients, and also in cosmetics, plastics, insecticides as well as environmentally, have a consistent influence that is added to dietary phytoestrogens, making it difficult to clearly separate the action of these two kind of agents in studies done on populations.

Avian studies
The consumption of plants with unusual content of phytoestrogens under extraordinary conditions, have shown to decrease fertility in quail. Parrot food as available in nature has shown only weak estrogenic activity. Studies on screening methods for environmental estrogens present in manufactured supplementary food, with the purpose to enable reproduction of endangered species. have been researched.

Food sources
According to a study by Canadian researchers about the content of nine common phytoestrogens in a Western diet, foods with the highest relative phytoestrogen content were nuts and oilseeds, followed by soy products, cereals and breads, legumes, meat products, and other processed foods that may contain soy, vegetables, fruits, alcoholic, and nonalcoholic beverages. Flax seed contained the highest total phytoestrogen content, followed by soy bean and tofu. The highest concentrations of Isoflavones are found in soy bean and soy bean products (eg. tofu), whereas lignans are the primary source of phytoestrogen found in nuts and oilseeds (e.g. flax).

Phytoestrogen content varies in different foods, and may vary significantly within the same group of foods (e.g. soy beverages, tofu) depending on processing mechanisms and type of soy bean used. Legumes (in particular soybeans), whole grain cereals, and some seeds are high in phytoestrogen. A more comprehensive list of foods known to contain phytoestrogens includes: soy beans, tofu, tempeh, soy beverages, linseed (flax), sesame seeds, wheat, berries, oats, barley, dried beans, lentils, rice, alfalfa, mung beans, apples, carrots, wheat germ, ricebran, soy linseed bread, ginseng, bourbon and beer fennel and anise

Health Risks and Benefits
In human beings, phytoestrogens are readily absorbed, circulate in plasma and are excreted in the urine. Metabolic influence is different than in grazing animals given the differences between ruminant versus monogastric digestive systems.

Because phytoestrogens may mimic endogenous estrogens,  there has been some unsubstantiated speculation that this similarity and the consumption of high quantities of phytoestrogens may result in hormonal imbalances and effects associated with excess estrogen levels. However the scientific studies which have been done do not support these concerns. The main reason why the dietary consumption of phytoestrogens is not considered a risk factor is that phytoestrogens do not appear to bioaccumulate.

Phytoestrogen in men
The covert and extensive use of phytoestrogens (as soy protein) in fast food meals and other processed foods for reducing the higher costs of true meat products, may however, lead to the unaware daily consumption of extreme quantities of isoflavonoids by fast food eaters. A research team at the Queen's University in Belfast, claims that such excess may lead to an slight decrease in male fertility, including a decrease in reproductive capability if isoflavones are taken in excess during childhood.

In theory, exposure to high levels of phytoestrogens in men could alter their hypothalamic-pituitary-gonadal axis, however, studies have shown that such a hormonal effect is minor. Isoflavones supplementation has no effect in sperm concentration, count or motility and show no changes in testicular or ejaculate volume. Researchers are studying if these mild effects may explain the protective effects of phytoestrogens in prostate cancer prevention.

Phytoestrogen in women
There are conflictive studies and results are unclear about the possibility that phytoestrogens may have any incidence in the development or avoidance of cancer in women. . While some clinical studies showed a protective effect against breast cancer, in vitro studies  concluded that women with current or past breast cancer should be aware of the risks of potential tumor growth when taking soy products, althought the potential for tumor growth was found related only with small concentration of genistein and protective effects were found with larger concentrations of the same phytoestrogen. A 2006 review article stated the opinion that not enough information is available, and that even if isoflavones have mechanisms to inhibit tumor growth, in vitro results justify the need to evaluate, at cellular level, the impact of isoflavones on breast tissue in women at high risk for breast cancer. The generally accepted position on this topic is that phytoestrogens may be beneficial for healthy women, however, women with cancer history should be aware of existing risks and avoid consumption until more information is available.

Phytoestrogen in infant formula
Some studies have found that diverse concentrations of isoflavones may cause effects on intestinal cells. At low doses, genistein acted as a weak estrogen and stimulated cell growth; at high doses, it inhibited proliferation and altered cell cycle dynamics. This biphasic response correlates with how genistein is thought to exert its effects. Some reviews express the opinion that more research is needed to answer the question of what effect phytoestrogens may have on infants, but did not find any adverse effects. Diverse studies conclude there are no adverse effects in human growth, development, or reproduction as a result of the consumption of soy-based infant formula. One of these studies, published at the Journal of Nutrition, concludes that: "...there is no clinical concerns with respect to nutritional adequacy, sexual development, neurobehavioral development, immune development, or thyroid disease. SBIFs provide complete nutrition that adequately supports normal infant growth and development. FDA has accepted SBIFs as safe for use as the sole source of nutrition"

Ethnopharmacology
In some countries, phytoestrogenic plants have been used for centuries in the treatment of menstrual and menopausal problems as well as for fertility problems. The plants most used have been those that have later shown higher content of phytoestrogens i.e. Pueraria mirifica, Angelica, fennel and anise.