Phytoestrogens

Phytoestrogens, sometimes called "dietary estrogens", are a diverse group of naturally occurring
nonsteroidal plant compounds that, because of their structural similarity with estradiol (17-β-
estradiol), have the ability to cause estrogenic or/and antiestrogenic effects.[1]

Chemical structures of the most common phytoestrogens found in plants (top and middle)
compared with estrogen (bottom) found in animals.

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 allow them to mildly mimic
and sometimes act as antagonists of estrogen[1]. Phytoestrogens were first observed in 1926 [1][2],
but it was unknown if they could have any effect in human or animal metabolism. In the 1940s it
was noticed for the first time that red clover (a phytoestrogens-rich plant) pastures had effects on
the fertility of grazing sheep.[1][3] 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,[1][3][4] though there is no evidence to support their use in
alleviating the symptoms of menopause.[5]

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.[1]
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.[6]

Contents
[hide]

• 1 Structure
• 2 Mechanism of action
• 3 Ecology
• 4 Avian studies
• 5 Food sources
• 6 Health risks and benefits
o 6.1 Males
o 6.2 Females
o 6.3 Infant formula
• 7 Ethnopharmacology
• 8 See also
• 9 External links

• 10 References

[edit] Structure
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[1]. 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.[7]

[edit] Mechanism of action

Phytoestrogens exert their effects primarily through binding to estrogen receptors (ER).[8] There
are two variants of the estrogen receptor, alpha (ER-α) and beta (ER-β) and many phytoestrogens
display somewhat higher affinity for ER-β compared to ER-α.[8]

The key structural elements that enable phytoestrogens to bind with high affinity to estrogen
receptors and display estradiol-like effects are:[1]

• 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).

[edit] Ecology
These compounds in plants are an important part of their defense system, mainly against fungi.[9]

Phytoestrogens are considered archiestrogens (ancient, naturally occurring) 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 [10] 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.[11]

[edit] Avian studies

The consumption of plants with unusual content of phytoestrogens under drought conditions, has
been shown to decrease fertility in quail.[12] Parrot food as available in nature has shown only
weak estrogenic activity. Studies have been conducted on screening methods for environmental
estrogens present in manufactured supplementary food, with the purpose to enable reproduction
of endangered species.[13]

[edit] 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 and
other oilseeds contained the highest total phytoestrogen content, followed by soybeans and tofu.
[14]
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.[15] 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,[16] wheat germ, rice bran, soy linseed bread, ginseng, hops[17], bourbon, beer[18],
fennel and anise.[19]

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.[20]

[edit] Health risks and benefits

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.[11]

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.

[edit] 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.[21]

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.[22]
Isoflavones supplementation has no effect on sperm concentration, count or motility, and show
no changes in testicular or ejaculate volume.[23][24]

[edit] Females

There are conflicting studies, and it is unclear if phytoestrogens have any effect on the cause or
prevention of cancer in females.[25][26] Epidemiological studies showed a protective effect against
breast cancer.[27] In vitro studies concluded that females with current or past breast cancer should
be aware of the risks of potential tumor growth when taking soy products, as they can stimulate
the growth of estrogen receptor-positive cells in vitro. 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.[28] 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 females at high risk for breast cancer.[29] 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.[30]
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.[31]

[edit] 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.[32]

Some reviews express the opinion that more research is needed to answer the question of what
effect phytoestrogens may have on infants,[33][34], but their authors did not find any adverse
effects. Multiple studies conclude there are no adverse effects in human growth, development, or
reproduction as a result of the consumption of soy-based infant formula compared to
conventional cow-milk formula.[35][35][36][37] While it should be noted that all infant formulas are
inferior to human milk, soy formula presents no more risk than cow-milk formula.[38] One of
these studies, published at the Journal of Nutrition,[37] concludes that:

"Comprehensive literature reviews and clinical studies of infants fed SBIFs [soy-based 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."[39]

[edit] 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.[40] Plants most that have
shown to contain phytoestrogens include Pueraria mirifica,[41] and its close relative, kudzu,[42]
Angelica,[43] fennel and anise.[19]

[edit] See also

• Isoflavones
• Lignan
• Soy
• Xenoestrogens
• Phytoserm