Thanks to:Radeep.K.R
INTRODUCTION
Epidemiological studies have revealed possible etiological factors responsible for various diseases. From these population-based studies around the world, it is now apparent that many common diseases of the prosperous nations are linked to diet and can be largely prevented by diet modification. This has renewed interest in the research of non-nutrient and nutrient bioactive compounds obtained from plant sources, which possess a wide range of biological properties that contribute to different health-related benefits. These phytochemicals are becoming increasingly recognized for maintaining good health both to clinical nutritionists and lay men. The phytoestrogens are naturally occurring plant derived non-steroidal compounds and are found in many foods2. Population-based studies have revealed that consumption of a phytoestrogen-rich diet, as seen with traditional Asiatic societies, is protective against so-called "Western" diseases such as breast, prostate, and bowel cancer and cardiovascular diseases. These compounds appear to be biomarkers of a 'healthy' diet. Apart from plant source, compounds with estrogen like activity are also found in animals (ovarian steroids),microorganisms (e.g., mycoestrogens from molds)1, as well as industrially manufactured estrogenic compounds such as bisphenol A and nonylpheno!4. Drugs like diethyl stilboesterol, estradiol benzoate etc. also have estrogenic activity. Wide range of compounds with estrogenic activity may be consumed due to their introduction into the food chain. One example is pesticides and insecticides,including DOT, which contain estrogen-like compounds. These compounds and several other environmental estrogens have been-classified as xenoestrogensS. The long-term effects of xenoestrogens are not known completely, however, there is a growing concern over their potentially deleterious effects on human health's. This review is focused on classification, mechanism of action, pharmacology,and various promising uses of phytoestrogens
SOURCE OF PHYTOESTROGENS
blackberry fruit-one of the source of phytoestrogens.
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.1J"-i 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.ill! 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, wheat berries, fenugreek, oais, barley, dried beans, lentils, yams, rice, alfalfa, mung beans, apples, carrots, pomegranates, ^ wheat germ, rice bran, soy linseed bread, ginseng, hops , bourbon, beer1 ' , 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
Table 1. Foods high in phytoestrogen content.
| Phytoestrogen food sources | Phytoestrogen content (µg/100g) |
| 379380 | |
| 103920 | |
| 27150.1 | |
| Soy yogurt | 10275 |
| Sesame seed | 8008.1 |
| Flax bread | 7540 |
| Multigrain bread | 4798.7 |
| Soy milk | 2957.2 |
| Hummus | 993 |
| Garlic | 603.6 |
| Mung bean sprouts | 495.1 |
| Dried apricots | 444.5 |
| Alfalfa sprouts | 441.4 |
| Dried dates | 329.5 |
| Sunflower seed | 216 |
| Chestnuts | 210.2 |
| Olive oil | 180.7 |
| Almonds | 131.1 |
| Green bean | 105.8 |
| Peanuts | 34.5 |
| Onion | 32 |
| 17.5 | |
| Corn | 9 |
| Coffee, regular | 6.3 |
| 2.9 | |
| Milk, cow | 1.2 |
Table 2. Total phytoestrogen and lignan content in vegetables,
fruits, nuts and drinks.
| Food items | Lignan content (µg/100g) | Total phytoestrogen (µg/100g) |
| Vegetables | ||
| Soy bean sprouts | 2.2 | 789.6 |
| Garlic | 583.2 | 603.6 |
| Winter squash | 113.3 | 113.7 |
| Green beans | 66.8 | 105.8 |
| Collards | 97.8 | 101.3 |
| Broccoli | 93.9 | 94.1 |
| Cabbage | 79.1 | 80 |
| Fruits | ||
| Dried prunes | 177.5 | 183.5 |
| Peaches | 61.8 | 64.5 |
| Strawberry | 48.9 | 51.6 |
| Raspberry | 37.7 | 47.6 |
| Watermelon | 2.9 | 2.9 |
| Nuts and other legume seeds | ||
| Pistachios | 198.9 | 382.5 |
| Chestnuts | 186.6 | 210.2 |
| Walnuts | 85.7 | 139.5 |
| Cashews | 99.4 | 121.9 |
| Hazel nuts | 77.1 | 107.5 |
| Lentils | 26.6 | 36.5 |
| Beverages | ||
| Wine, red | 37.3 | 53.9 |
| Tea, green | 12 | 13 |
| Wine, white | 8 | 12.7 |
| Tea, black | 8.1 | 8.9 |
| Coffee, decaf | 4.8 | 5.5 |
| Beer | 1.1 | 2.7 |
| Other | ||
| Black bean souce | 10.5 | 5330.3 |
| Black licorice | 415.1 | 862.7 |
| Bread, rye | 142.9 | 146.3 |
CLASSIFICATION OF PHYTOESTROGENS
Classification
Phytoestrogens are manily classified into three classes. They are isoflavonoids, coumestans and lignans.
Isoflavonoids –
1) diadzein
2)genistein
3) glycetein
Coumestans-
1) coumesstrol
Liganans –
1) Enterolactone
2) Enterodione
Isoflavonoid
Isoflavonoids are the major class phytoestrogen which are primarily found in the fabaceae family which include peanut and clover , and also in the tridaceae and euphorbiaceae family isoflavones fexist in nature in the inactive form as glycones, the are redly hydrolysed in the gut by the action of B- glucosidases to aglycones. Which in turn are easily absorbed through the intestinal epithelial cells. They are transported to the liver reconjugated and excreted in urine and bile as occurs for the enterohepatic circulation of estrogens . The mainly occurring isoflavanoids in the nature are diadzein, genistein and glycetein.
Genistein - first identified isoflavone was genistein in dyer’s broom (genista tinctoria ) and heather (calluna vulgaris) at the end of 19th centary. It represents aglycon of genistin and sophoricoside.The characteristic features of genistein include.
.1) It lowers the incidence of breast, prostrate and several other carcinomas
2) It minimizes the incidence and number of cancerous tumours. And also to enhance the latency in the animal model of cancer.
3) In cell –culture model it particularly inhibit proliferation of certain types of cancer cells.
4) various sophisticated well defined techniques have been adopted
Coumestans
Coumostans are the other class of phytoestrogen found in nature . There is a large number of coumestans but few of those isolated from plants have show estrogenic activity. Among which coumestrol important for humans. Coumosterol is an estrogenic factors occurring naturally in forage crops, especially in landino clover,
strawberry clove and alfalfa.
Liganans
Liganans are abundantly occurring phytoestrogen which have been obtained from the root, heart, wood, foliage, fruit and resinous exudates of plants as date flax seed is established to be the richest dietary sources for the liganans. ( 0 .96 – 3.15 mol liganans/g) The other sources are whole grains, vegetables, tea, strawberries and cranberries. Lignans are necessary for the formation of the of constituent of the plant cell wall. Lignin exist in nature in their inactive form secoisolaricerisinol and matariresinol. Which are readily converted into their estrogenic compounds. The mammalian lignans enterodiol and enterolactone, respectively through reaction catalysed by bacteriall enzymes. Mammalian lignans production then depends on the presences of intestinal bacteria. It is thought that the primary sites of their production are the cecum and colon in 2002 raffaelli et al (raffaelli et al 2002) reviewed 144 references on mammalian lignans. The biological activities described include antioxida. Antitumor. Weakly estrogenic and antiestrogenic properties, and they are suggested to have protective against postmenopausal osteoporosis, as wellas hormonerelated cancer and cardiovascular diseases.
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Mechanisms of Action of Phyto-Estrogens
ER-mediated mechanisms of action. The oestrogenic activity of
isoflavones was first described inthe 1940s when the infertility of sheep in Western Australiawas proposed to be caused by ingestion of clover pastures rich in the isoflavone precursors Using an Estrogen receptor (ER)-dependenttranscriptional response assay, reported that of the isoflavoneprecursors, genistein had the highest oestrogenicity compared with daidzein, It is this oestrogenic activity that is thought to be mainly responsiblefor several of the beneficial effects of isoflavones in hormone-dependent processes, such as reducing bone loss associated with osteoporosis, improving menopausalsymptoms, and lowering levels of plasma low densitylipoprotein (LDL) (which accumulates in blood vessel wallsduring arteriosclerosis). There are two types of ER, ER-Yand ER-Z encoded by distinct genes: ER - Y and ER - Z appear to serve distinct biological roles, as judged from the different phenotypes of mice devoid of each gene alone and the fact that they differ in the C-terminal ligand-binding domain and the N-terminal transactivation domain. ER- Z is mainly expressed in non reproductive tissues, such as the vascular system and bone, and seems to mediate in part the impact of oestrogens on the vasculature and the growth promoting effects of oestrogens on non gonadal tissues. By contrast, ER- Y is responsible for the classical hormonal effects, such as endometrial proliferation and mammary enlargement. Following ligand binding, the ER dimerises before binding to target genes and modulating transcription. Ctivated ERs regulate transcription of target genes either directly by binding to regulatory DNA elements or indirectlyby modulating the expression of other transcription factors, such as AP-1 or NF-B. Thus, ERs can trans activate AP-1- or NF-B-responsive genes . The oestrogenic potency of isoflavones is low compared with 17- Z oestradiol, as soy isoflavones have ~1/3 and 1/1000 of the affinity of 17- Zoestradiol for ER - Z and ER- Y, respectively. Since genistein possesses a much higher binding affinity for ER-Z than for ER-Y, isoflavones can be regarded as a type of natural ‘selective ER modulator’ (SERM). However, recent Xray crystallographic studies examining the interaction of oestrogens, raloxifene and genistein with ERZ suggest that the orientation of raloxifene and genistein with ERZ is different from that of oestradiol, in particular in the interaction with helix 12 of the receptor .Isoflavones lack specific lipophilic regions, which
undoubtedly affect their ER-Z-binding ability and the subsequent initiation of cellular events. Role of phyto-oestrogen in the treatment of breast cancer In vitro studies have established that phyto-oestrogens are weakly oestrogenic, since they have the ability to bind to mammalian oestrogen receptors to a low degree. Their affinity to receptors (from rabbit, sheep and rat uterine receptors, and a human cancer cell line) has been compared with oestradiol. Coumestrol has the greatest affinity, only ten to twenty times lower than oestradiol, and genistein about 100 times less; daidzein and equol bind about 1000 times less
Oestrogen-dependent mechanisms
receptor Y and oestrogen receptor Z –mediated mechanisms. Phyto-oestrogens appear to exert biphasic effects on breast cancer cell growth in vitro implicating differential mechanisms of action. At low concentrations (1–10 mM), cell proliferation is stimulated in ER(þ) cell lines only, suggesting that the phytooestrogens are acting via the ER. This idea is strengthened by the finding that phytoestrogenscan induce pS2 expression in MCF-7 cells. Both the ER-Y and ER-Z forms could be involved in the stimulation of cell proliferation by phyto-oestrogens. At low concentrations genistein and quercetin have been shown to be full agonists for ER-Y as well as ER-Z. It is possible therefore that phytooestrogens may exert their effects at the cellular level via a similar mechanism of action to that of oestradiol. It is thoughtthat the binding of oestradiol to the ER results in a conformational change, which enables binding of the oestradiol–ER complex to the oestrogen response element on the DNA. Activation of the oestrogen response element mayinduce the expression of the growth-related proto-oncogene c-fos, forming a c-fos–c-jun heterodimer that activates the activation protein-1 site, leading to cell proliferation
Oestrogen independent mechanisms
There are several other anti-cancer effects of isoflavoneswhich are not related to their anti-oestrogenic properties.Genistein is known to inhibit tyrosine kinases, which areresponsible for phosphorylating proteins required for the regulation of cell functions, including cell division. Hence, it has been shown to inhibit growth in many cell lines. These lines include those which do not have oestrogen receptors,which suggests that these effects may be independent of any anti-oestrogen effects. Genistein has also been shown to inhibit the DNA repair enzyme topoisomerase, and to act as an antioxidant, thus potentially preventing oxidative DNA damage. In one cell line, genistein has been shown to cause changes characteristic of apoptosis, or programmed cell death, a protective mechanism induced in cells that have been damaged in order to prevent the proliferation of harmful mutations and possibly cancer. It has also been shown to inhibit ras gene expression in a rat pheochromocytoma cell line. In addition, genistein has been shown to inhibit angiogenesis, the formation of new blood vessels, an abnormal event which occurs as part of the growth and expansion of malignant tumours. It has been pointed out that many of these effects have been shown with very high concentrations, and not in cells treated with thelevels likely to be achieved in plasma of human subjects eating foods containing Phytoestrogens
USE OF PHYTOESTROGENS
USE OF PHYTOESTROGENS
Phytoestrogens are mainly used in the treatment of
1, Cancer
2, cardiovascular diseases
3, osteoporosis
1)In the treatment of cancer
Pytoestrogen act as potential anticancer agent which can inhibit wide range of both hormone dependent and hormone independent cancer cells. The risk of development of breast cancer may be decreased by isoflavones . They are a class of phytoestrogen derived from soya bean . They can stimulate the proliferation of ER -alpha dependent breast cancer cell line at lower concentration whereas high concentration they exert strong cytotoxic effect.
The epidemiological studies support the role of phytoestrogen in reducing the risk of prostate cancer. Here also the drugs used are isoflavonoids, Among which drug of choice is Genistein. It lowers the incidence of prostate, uterine and breast cancer. Isoflavonids shows to inhibit the prostate cancer cell by almost 30 % Lignans are other class of phytoestrogen which may reduce the risk of cancer in females.
2)In the treatment of cardiovascular diseases
The epidemiological data suggest that phytoestoge consumption contributes to the lower incidence of cardiovascular diseases. The can act as cardioprotective. Phytoestrogen also appears to play protectiv role in atherosclerosis. Genistein has marked effect in cardiovascular diseases. It act by regulating the low density lipoprotein (LDL) concentration, but do not change high density lipoprotein (HDL) concentration. As a result cardiovascular diseases can be prevented other mechanisms by which phytoestrogens exert cardio protective effects include inhibition of coagulation process. Inhibition of tyrosine kinase and inhibition of platelet aggregation.
3)In the treatment of osteoporosis
Phytoestrogen can be used to prevent bone loss due to estrogen deficiency. This effect may be related to bone estrogen receptor agonist activity or effects on osteoblasts and osteoclasts. Isoflavone supplementation can stimulate bone formation with the doses below 90 mg/d in twelve weeks
Other effects
1) Phytoestrogens improve in brain function and cognitive performance
2) They have marked protective effective in the prevention of thyroid, lung, stomach ache, colon and skin cancer.
3) They regulate menstrual cycle in women and relieve menopausal symptom at a recommended dose of 10 -30 mg /d.
4) No effects on hot flushes have been observed and placebo effect has been over 50 %.
5) They are also being used as anti aging agent
6) Lignan are recognized as a cytotoxic agent which is mostly used to treat the venereal warts and they are also acting as antioxidant.
PHYTOEOSTROGENS AS POTENTIAL THERAPUTIC AGENTS
1.CANCER
Within past few years, phytoestrogens have attracted considerable attention for their potential anticancer activity. Since almost all anticancer drugs have serious side effects, there is search for "natural" alternatives or complements to traditional therapy. Further, the increased enthusiasm in phytoestrogens as potential anticancer agents is evidenced by the published data. The population-based studies show that the mortality due to breast, ovarian, prostate, and colon cancer has a negative correlation with the phytoestrogens and cereal intake in the diet. There are hundreds of in vitro studies, which show that phytoestrogens can inhibit a wide range of both hormone-dependent and hormone-independent cancer cells.
The human estrogen receptors (ER) are of two types - ER-alpha and ER-beta. Both subtypes differ in the C-terminal ligand-binding domain and in the N-terminal trans activation domain. Like estrogens.phytoestrogens also bind to both ER-alpha and Erbeta (but more strongly to ER-beta). The phytoestrogens can mimic and in some cases, antagonise the effects of endogenous estrogens. Based upon recent data of their conformational binding to ER-alpha and ER-beta, and showing both agonistic and antagonistic effects, the phytoestrogens have been argued to be considered as selective estrogen receptor modulators (SERMs). Apart from hormonal actions, phytoestrogens also modulate a diverse array of intracellular signal transduction cascades. Genistein has been most widely studied. It has been shown to inhibit plasma protein tyrosine kinases and DMA topoisomerases (I and II). In vitro studies, genistein increased the concentration of transforming growth factor-beta. It also exhibited antioxidant property. In addition, genistein has been shown to inhibit angiogenesis. All of these activities may contribute to the effectiveness of genistein and possibly other phytoestrogens as potential anticancer agents. Current evidence suggests that the protective effect of phytoestrogens is unlikely to be brought about via stimulation of sex hormone binding globulin (SHBG) and thereby reducing the free estrogen levels in plasma.
The risk of development of breast cancer may be decreased by isoflavones. Both tumerogenic and antitumerogenic effects of phytoestrogens have been reported. At lower concentration, they tend to stimulate the proliferation of two ER-alpha-dependent breast cancer cell lines; whereas, at high concentration, they exert strong cytotoxic effect. Further, in breast cancer patients, low levels of lignans in urine have been reported which is considered as a measure of low fibre intake. In other studies, high plasma and urinary levels of phytoestrogens were found in Japanese women consuming traditional vegetarian diet and it was observed that there is low incidence of breast, endometrial and ovarian cancers in these groups. Recent study attempted to correlate urinary phytoestrogens with breast cancer risk in 88 breast cancer patients. In this study, it was found that high urinary excretion of genistein and enterolactone was weakly and non-significantly associated with reduced risk of breast cancer. Overall, though experimental and epidemiological studies are promising, more research is required to validate the role of phytoestrogens in the prevention of breast cancer. The prostate cancer is an age related disorder and it is responsive to estrogen therapy. Various studies have been conducted to link prostate cancer with diet intake, and like breast cancer, it is also comparatively rare in Far Eastern populations consuming soybean. It has been observed that the incidence of prostate cancer is low in countries in which phytoestrogens intake is high. The epidemiological studies also support the role of phytoestrogens in reducing the risk of prostate cancer. A recent study reported that short-term administration of phytoestrogen supplement in healthy male volunteers had no observable effect on the endocrine measurements, testicular volume or semen quality.ln animal models, the studies investigating the effects of soybean have shown reduced tumerogeriesis. The tumor development in animals implanted with prostate cancer cells was significantly reduced by feeding phytoestrogen rich-diet. The genistein has been shown to inhibit the activity of 5-alpha reductase enzyme in the genital skin fibroblasts and benign hyperplastic prostate tissues in vitro. This enzyme converts testosterone into dihydrotestosterone, which stimulates the growth of prostate tissue. In prostate cancer, one treatment option is combined androgen blockade using estrogen agonists, luteinizing hormone releasing hormone (LHRH) agonists and non-steroidal anti-androgens. One indicator for androgen blockade is inhibition of production of androgen regulated proteins, including prostate-specific antigen. One recent study showed that there was a significant blockade of this androgen-regulated protein in prostate cancer cell lines. Thus, by looking at in vitro, animal and epidemiological studies, it may be suggested that dietary phytoestrogens may play a protective role in the prevention of prostate cancer.
2. CARDIOVASCULAR DISORDERS
The mortality due to cardiovascular disorders is similar in men and women. The serum cholesterol levels are low in women up to the age of 50 years as compared with men; however, after menopause, the serum cholesterol in women exceeds that of men. The elevated cholesterol levels accompanied by loss of endogenousestrogen secretion increases the risk of developing coronary artery disease (CAD) in postmenopausal women, de Kleijn et al. studied the relationship between dietary phytoestrogen intake and metabolic cardiovascular risk factors in postmenopausal women and observed that high intake of phytoestrogens is associated with a favorable metabolic cardiovascular risk profile. Current evidence suggests that phytoestrogens have a significant potential in reducing CAD via favorable effects on the lipid profile. The serum total, LDL, and VLDL cholesterol levelshave been shown to be significantly lower in bothmale and female rhesus monkeys fed on phytoestrogen rich diet.The epidemiological data also suggests that phytoestrogen consumption contributesto the lower incidence of cardiovascular diseasein Asian countries and in vegetarians and that phytoestrogens may be cardioprotective. A randomised double-blind placebo controlled study in 96 normotensive men and 83 postmenopausalwomen (total 179 subjects) revealed that phytoestrogens improve blood pressure and lipid profile but, overall, did not improve the vascular function.Phytoestrogens also appear to play protective role in atherosclerosis. Data from animal studies suggests that phytoestrogens inhibit plaque progression.In another study, it was found that genisteinupregulated matrix protein expression, which may be related to the plaque formation. Inhibiting cell adhesion and altering the activity of specific growth factors may slow the plaque formation by phytoestrogens. The mechanism of cardioprotective effects of phytoestrogens is uncertain. Genistein has beenreported to both up- and down-regulate LDL-receptors. The phytoestrogens may modulate the lipoprotein metabolism due to their estrogenic activity. The antioxidant property of phytoestrogens may also contribute to reducing the oxidation of lipids as evidenced by a recent study in healthy volunteers. The estrogen administration can increase HDL-cholesterol, thus prevent cardiovascular disease.The phytoestrogens also tend to regulate the cholesterol homeostasis by increasing fecal bile acid secretion, altering bile acid synthesis rates and increasing hepatic cholesterol secretion. Other mechanisms by which phytoestrogens exert cardioprotectiveeffects include inhibition of coagulation process, inhibition of tyrosine kinase and inhibition of platelet aggregation.
3.OSTEOPOROSIS
In postmenopausal women, estrogen deficiency is a major risk factor for osteoporosis. The incidence of hip fracture increases and may lead to immediate disability. It has been observed that osteoporosis and risk of hip fracture is low in postmenopausal Japanese women than their Western counterparts. The hormone replacement therapy(HRT) is proven for lowering the risk of cardiovascular disease and osteoporosis. Due to increased riskof certain types of cancers or contraindications in HRT, phytoestrogens may act as 'natural alternatives' to HRT. A diet rich in phytoestrogens has been shown to be accompanied by an increase in bone mineral density (BMD). Recent study carried out amongChinese pre- and post-menopausal women demonstrated that high isoflavone diet is associated with high BMD (at both spine and hip region) in post- but not in pre-rnenopausal women. Another longitudinal study investigated the effect of soy isoflavones intake on the maintenance of peak bone mass in a cohort of Asian women and showed that soy intake has a positive effect on the maintenance of spinal BMD. Studies carried out in ovariectomised rat model of osteoporosis to evaluate the role of phytoestrogens in preventing bone loss due to estrogen deficiency are also convincing.Recent discovery of ER-beta in osteoblast cells may explain the protective role of phytoestrogens in bone loss, however, non-hormonal mechanisms have also been suggested. It is well recognised that estrogens can down-or up-regulate the activity of osteoclasts, thereby limiting the bone resorption. However, the exact mechanism of action is not clear. The phytoestrogens have a conservatory effect on calcium excretion. Isoflavones have been proposed to inhibit activities of osteoclast-like cells by interfering with tyrosine kinase activity of epidermal growth factor receptor protein. In vivo and in vitro studies indicate that osteoclast formation and bone resorption are enhanced due to the generation of free radicals. Since phytoestrogens have been reported to exert antioxidant properties, they may reduce the rate of bone loss in postmenopausal women partly by antioxidant effects. Considering animal and human data to date, phytoestrogens appear to exert protective effect on bone. Ipriflavone (7-isopropoxy isoflavone) is a synthetic isoflavone, having similar chemical structure to diadzein and genistein, and former is one of its active metabolite. It has been reported to prevent bone loss in postmenopausal women in doses of 600 mg/day and can be used as an
alternative to HRT in estrogen-deficient states.
OTHER EFFECTS
The isoflavones have been found to be potent inhibitors of human aldehyde and alcohol dehydrogenase isozymes and it is proposed that they might be useful in the treatment of alcohol abuse. Since HRT is thought to improve cognitive functionand perhaps reduce the onset of dementia in postmenopausal women, phytoestrogens may play a positive role in these conditions. File et al. evaluated the role of phytoestrogens on memory, attention and frontal lobe function in healthy volunteers and found improved cognitive performance. The improvement in brain function has also been reported in animal studies, which is recently reviewed by Lephart et al. . The consumption of phytoestrogens has been shown to be protective in the prevention of thyroid, lung, stomach, colon, and skin cancers, however, further research is warranted at this time. There is increasing evidence that phytoestrogens may be beneficial in chronic renal disease. Menstrual cycle characteristics are regulated by phytoestrogens. Menstrual cycle length is one of the risk factors for breast cancer, however, this association is not clear. Because menstrual cycle of Japanese and Chinese women is significantly longer and is inversely related to breast cancer risk, therole of phytoestrogens may be considered protective in disease prevention. Apart from this, various clinical trials have been conducted in postmenopausal women aimed at evaluating the effects of soy foods on hot flushes and vaginal cytology with variable but promising results. Wilcox et al. investigated the effects of phytoestrogens on vaginal cytology, and found an increase in cell proliferation, which is an indication of estrogenic activity with reversal of menopausal atrophy.
CONCLUSION
The global movement for consuming phytoestrogensrichdiet is increasing and tabletized concentratedisoflavone extracts are being promoted heavily. This is because epidemiological data and animal, human and in vitro studies support the role of phytoestrogens in lowering the risk of various types of cancers (especially breast and prostate cancer) and cardiovascular disease. However, contradicting reports are also emerging simultaneously, which is creating confusion. Due to this, there is difficulty in making wide spread recommendations about dietary intake of phytoestrogens. Thus, more research is required to establish the role of phytoestrogens in above discussed conditions. Evaluation of benefits and risks of phytoestrogens is a complex task due to inter-individual variation and complexity in absorption and metabolism. Overall, it is na'i've to assume that consumption of phytoestrogens may be good. On the other hand, inappropriate or excessive use may be detrimental. Before making widespread recommendations for phytoestrogens intake, extensive data on specific intracellular effects, duration of exposure and disease, and results from prospective randomised studies in humans is essential. It is also necessary to determine the potential side effects of phytoestrogens. Among various phytoestrogens, isoflavones (genistein and diadzein) have been most studied. Studies on lignans are few and for coumestans very few. This might be due to lack of industrial funding and problems in analytical techniques. Study of effects of individual compounds in various clinical conditions is the need of the hour. Based on dietary phytoestrogens, structure activity relationship studies should be carried out and more synthetic and semisynthetic compounds (like ipriflavone) should be evaluated. Genetic modification of soybean and other plants and improvement in food technology to enhance phytoestrogen production is inevitable.
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