Phytoestrogens are xenoestrogens which means foreign substances functioning as the primary female sex hormone (see estrogen) not generated within the endocrine system but consumed by eating phytoestrogonic plants. Also called "dietary estrogens", are a diverse group of naturally occurring nonsteroidal plant compounds that, because of their structural similarity with estradiol (17-??-estradiol), have the ability to cause estrogenic or/and antiestrogenic effects. The plants use the phytoestrogens as part of their natural defence against the overpopulation of the herbivore animals by controlling the male fertility .

Their name comes from the Greek phyto = plant and estrogen , the hormone which giving fertility to the female mammals (for "estrus" -Greek ??????????????- meaning sexual desire and "gene" -Greek ????????- for "to generate").

The similarities, at molecular level, of estrogens and phytoestrogens allow them to mildly mimic and sometimes act as antagonists of estrogen Researchers are exploring the nutritional role of these substances in the regulation of cholesterol, and the maintenance of proper bone density post- menopause. Evidence is accruing that phytoestrogens may have protective action against diverse health disorders, such as prostate, breast, bowel, and other cancers, cardiovascular disease, brain function disorders and osteoporosis,

Phytoestrogens cannot be considered as nutrients, given that the lack of these in diet does not produce any characteristic deficiency syndrome, nor do 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.

Phytoestrogens mainly belong to a large group of substituted polyphenolic compounds : 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 they are not flavonoids. Mycoestrogens have similar structures and effects, but are not components of plants; these are mold metabolites of Fusarium, a fungus 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 exert their effects primarily through binding to estrogen receptors (ER). There are two variants of the estrogen receptor, alpha ( ER-?? ) and beta ( ER-?? ) and many phytoestrogens display somewhat higher affinity for ER-?? compared to ER-??.

The key structural elements that enable phytoestrogens to bind with high affinity to estrogen receptors and display estradiol-like effects are:

• The phenolic ring that is indispensable for binding to estrogen receptor

• 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 that 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 affect the bioavailability of sex hormones by binding or stimulating the synthesis of sex hormone binding globuline (SHBG).

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

Phytoestrogens are ancient naturally occurring substances, and as dietary phytochemicals they are considered as co-evolutive with mammals. In the human diet, phytoestrogens are not the only source of exogenous estrogens. Xenoestrogens (novel, man-made), are found as food additives and ingredients, and also in cosmetics, plastics, and insecticides. Environmentally, they have similar effects as phytoestrogens, making it difficult to clearly separate the action of these two kind of agents in studies done on populations.

The consumption of plants with unusual content of phytoestrogens under drought conditions, has been shown to decrease fertility in quail.

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 and other oilseeds contained the highest total phytoestrogen content, followed by soybeans and tofu. The highest concentrations of isoflavones are found in soybeans and soybean products followed by legumes, whereas lignans are the primary source of phytoestrogens found in nuts and oilseeds (e.g. flax) and also found in cereals, legumes, fruits and vegetables.

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 soybean used. Legumes (in particular soybeans), whole grain cereals, and some seeds are high in phytoestrogens.

A more comprehensive list of foods known to contain phytoestrogens includes:

soybeans,

tofu,

tempeh,

soy beverages,

linseed (flax),

sesame seeds,

wheatberries,

fenugreek,

oats,

barley,

dried beans,

lentils,

yams ,

rice,

alfalfa,

mung beans,

apples,

carrots,

pomegranates,

wheat germ,

rice bran,

soy linseed bread,

ginseng, hops,

bourbon , beer,

fennel and anise.

An epidemiological study of women in the United States found that the dietary intake of phytoestrogens in healthy post-menopausal Caucasian women is less than one milligram daily.

In human beings, phytoestrogens are readily absorbed, circulate in plasma and are excreted in the urine. Metabolic influence is different from that of grazing animals due to the differences between ruminant versus monogastric digestive systems.

In the last few years, there has been a great deal of research into the possible beneficial effects of phytoestrogens in both diabetes and coronary heart disease.

Males

The use of phytoestrogens (as soy protein) in fast food meals and other processed foods as a low-cost substitute for meat products may lead to excessive consumption of isoflavonoids by fast food eaters. A research team at the Queen's University in Belfast, in a review article, speculate that such intake may lead to a 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 males could alter their hypothalamic-pituitary-gonadal axis. However, studies have shown that such a hormonal effect is minor.

Females

There are conflicting studies, and it is unclear if phytoestrogens have any effect on the cause or prevention of cancer in females. Epidemiological studies showed a protective effect against breast cancer. A Cochrane Review of the use of phytoestrogens to relieve the vasomotor symptoms of menopause ( hot flashes) demonstrated that there was no evidence to suggest any benefit to their use.

HRT may also be effective at reversing the effects of aging on muscle. A future aim is to target therapy to molecular mechanisms that work specifically in selected tissues.

Infant formula

Some studies have found that some concentrations of isoflavones may have 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, One of these studies, published at the Journal of Nutrition, concludes that:

"Comprehensive literature reviews and clinical studies of infants fed SBIFs infant formulas have resolved questions or raise 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"

Clinical guidelines from the American Academy of Pediatrics state: "although isolated soy protein-based

formulas may be used to provide nutrition for normal

growth and development, there are few indications

for their use in place of cow milk-based formula.

These indications include (a) for infants with galactosemia

and hereditary lactase deficiency (rare) and

(b) in situations in which a vegetarian diet is preferred."

In some countries, phytoestrogenic plants have been used for centuries in the treatment of menstrual and menopausal problems, as well as for fertility problems. Plants used that have been shown to contain phytoestrogens include Pueraria mirifica, Angelica, fennel and anise.

In a rigorous study, the use of one such source of phytoestrogen, red clover , has been shown to be safe, but ineffective in relieving menopausal symptoms.)

• Isoflavones

• Lignan

• Soy

• Xenoestrogens

• Phytoserm

• Phytoestrogen food sources

• Phytoestrogen content in food

• Phytoestrogens at e.hormone , a website of the Tulane/Xavier Center for Bioenvironmental Research