Phytoestrogen Content Research Articles

Variations in Plasma Phytoestrogen Concentrations in European Adults

Dietary phytoestrogens may play a role in chronic disease occurrence. The aim of our study was to assess the variability of plasma concentrations in European populations. We included 15 geographical regions in 9 European countries (Denmark, France, Germany, Greece, Italy, Spain, Sweden, The Netherlands, and UK) and a 16th region, Oxford, UK, where participants were recruited from among vegans and vegetarians. All subjects were participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma concentrations of 3 isoflavones (daidzein, genistein, and glycitein), 2 metabolites of daidzein [O-desmethylangolensin (O-DMA) and equol] and 2 mammalian lignans (enterodiol and enterolactone) were measured in 1414 participants. We computed geometric means for each region and used multivariate regression analysis to assess the influence of region, adjusted for gender, age, BMI, alcohol intake, smoking status, and laboratory batch. Many subjects had concentrations below the detection limit [0.1 μg/L (0.4 nmol/L)] for glycitein (80%), O-DMA (73%) and equol (62%). Excluding subjects from Oxford, UK, the highest concentrations of isoflavones were in subjects from the Netherlands and Cambridge, UK [2–6 μg/L (7–24 nmol/L); P < 0.05], whereas concentrations for lignans were highest in Denmark [8 μg/L (27 nmol/L); P < 0.05]. Isoflavones varied 8- to 13-fold, whereas lignans varied 4-fold. In the vegetarian/vegan cohort of Oxford, concentrations of isoflavones were 5–50 times higher than in nonvegetarian regions. Region was the most important determinant of plasma concentrations for all 7 phytoestrogens. Despite the fact that plasma concentrations of phytoestrogens in Europe were low compared with Asian populations, they varied substantially among subjects from the 16 different regions.

Phytoestrogens levels determination in the cord blood from Malaysia rural and urban populations

This study is a result of an analysis of free and conjugated phytoestrogens daidzein, genistein, daidzin, genistin and coumesterol in human cord blood plasma using LCMS. Cord blood was collected from urban and rural populations of Malaysia ( n = 300) to establish a simple preliminary database on the levels of the analyzed compounds in the collected samples. The study also aimed to look at the levels of phytoestrogens in babies during birth as this may have a profound effect on the developmental process. The sample clean up was carried out by solid-phase extraction using C18 column and passed through DEAE sephadex gel before analysis by LCMS. The mean concentrations of total phytoestrogens were daidzein (1.4 ± 2.9 ng/ml), genistein (3.7 ± 2.8 ng/ml), daidzin (3.5 ± 3.1 ng/ml), genistin (19.5 ± 4.2 ng/ml) and coumesterol (3.3 ± 3.3 ng/ml). Distribution of phytoestrogen was found to be higher in samples collected from rural areas compared to that of urban areas.

Adult-only exposure of male rats to a diet of high phytoestrogen content increases apoptosis of meiotic and post-meiotic germ cells

Apoptosis plays a critical role in regulating sperm production. Removal of androgens and gonadotropins, or estrogen administration induces germ cell apoptosis. It is hypothesized that dietary phytoestrogens increase apoptosis of developing germ cells, decreasing sperm production. This study aimed to test this in rats fed a high phytoestrogen diet only during adulthood. Male Wistar rats used in this study were offspring of females maintained on a low phytoestrogen diet prior to conception through to weaning. After weaning, juveniles were fed the same low phytoestrogen diet into adulthood. A cohort of males were transferred to a high phytoestrogen diet for 24 days and subsequently testes were collected from all animals. In the high phytoestrogen fed group, homogenization-resistant sperm counts were significantly decreased, as were epididymal sperm counts. Morphometric analysis determined round and elongated spermatid volumes to be significantly decreased, but seminiferous tubule lumen diameters to be significantly increased. TUNEL analysis determined that apoptosis of spermatocytes and round spermatids was significantly greater in the high phytoestrogen fed rats. Neither plasma gonadotropin concentrations nor testicular testosterone were altered. In conclusion, exposure of the adult male rat to a high phytoestrogen diet disrupts spermatogenesis, increasing germ cell apoptosis. This effect is independent of the hypothalamo-pituitary-testicular axis and is likely due to disruption of estrogen's actions in the testis.

The Feed Factor: Estrogenic Variability in Lab Animal Diets

Animal studies have long been a cornerstone of biomedical and environmental health research, and scientists need assurance that animals used in these studies are being cared for in ways that will not unknowingly influence experimental outcomes. But a growing number of scientists have voiced concern over the possibility that certain estrogenic compounds present in lab animal feed may skew test results. These compounds are deemed potentially problematic because they can bind to estrogen receptors and induce estrogen-like effects in animals, humans, and cells grown in culture. Some experts have advocated strict standardization of rodent chows and even the removal of dietary phytoestrogens. This emergent controversy was the focus of “DIET II—The Effect of Variability in Estrogenic Activity of Commercial Animal Feeds: Interaction with Manufacturers, NIH Officials, and Scientific Societies to Develop a Solution,” a full-day meeting held 3 August 2006 in Research Triangle Park, North Carolina. The meeting, the second in a series on the topic, was cosponsored by the NIEHS and the NIH Office of Dietary Supplements (ODS). Discussions at the meeting centered on the variation in estrogenic activity between feed batches, the effects of these estrogenic components on endocrine-related end points, and the difficulties inherent in comparing, interpreting, and reproducing these end points over time within and between different laboratories when background levels of diet-related estrogenic activity are not adequately documented. Findings presented at this meeting made it clear that researchers studying estrogen-related end points can not afford to overlook the influence of the test rodent’s diet. “This workshop is an excellent example of the cumulative and self-correcting nature of the scientific process,” said ODS nutritionist Elizabeth Yetley, a conference co-organizer. “That is, through the accumulation of results from a body of experimental evidence, the importance of approaches for better-defined animal diets relative to their potential estrogenic activity have been identified, and measures to improve future research in this area are being undertaken by the scientific community.” Participants at the conference—organized by NIEHS scientists Jerrold Heindel and Julius Thigpen, along with Yetley and University of Missouri–Columbia biologist Frederick vom Saal—included investigators from the endocrine disruptor research community as well as representatives from animal feed companies. This spectrum of representatives reflected the fact that, in Heindel’s words, “researchers and animal care divisions of research institutions are beginning to pay attention to the phytoestrogen issue, and feed manufacturers want to know what the scientific community wants.” Heindel described a sincere interest on the part of both sides to reach a “win–win” solution, one that would yield animal diets of a known estrogenicity that could be used by researchers in all fields of physiology and toxicology, but that also would not unduly burden the feed manufacturers.

Tools to evaluate estrogenic potency of dietary phytoestrogens:A consensus paper from the EU Thematic Network “Phytohealth” (QLKI-2002-2453)

Phytoestrogens are naturally occurring plantderived polyphenols with estrogenic potency. They are ubiquitous in diet and therefore, generally consumed. Among Europeans, the diet is rich in multiple putative phytoestrogens including flavonoids, tannins, stilbenoids, and lignans. These compounds have been suggested to provide beneficial effects on multiple menopause-related conditions as well as on development of hormone-dependent cancers, which has increased the interest in products and foods with high phytoestrogen content. However, phytoestrogens may as well have adverse estrogenicity related effects similar to any estrogen. Therefore, the assessment of estrogenic potency of dietary compounds is of critical importance. Due to the complex nature of estrogenicity, no single comprehensive test approach is available. Instead, several in vitro and in vivo assays are applied to evaluate estrogenic potency. In vitro estrogen receptor (ER) binding assays provide information on the ability of the compound to I) interact with ERs, II) bind to estrogen responsive element on promoter of the target gene as ligand-ER complex, and III) interact between the co-activator and ERs in ligand-dependent manner. In addition, transactivation assays in cells screen for ligand-induced ERmediated gene activation. Biochemical in vitro analysis can be used to test for possible effects on protein activities and E-screen assays to measure (anti)proliferative response in estrogen responsive cells. However, for assessment of estrogenicity in organs and tissues, in vivo approaches are essential. In females, the uterotrophic assay is applicable for testing ERa agonistic and antagonistic dietary compounds in immature or adult ovariectomized animals. In addition, mammary gland targeted estrogenicity can be detected as stimulated ductal elongation and altered formation of terminal end buds in immature or peripubertal animals. In males, Hershberger assay in peri-pubertal castrated rats can be used to detect (anti)androgenic/ (anti)estrogenic responses in accessory sex glands and other hormone regulated tissues. In addition to these short-term assays, sub-acute and chronic reproductive toxicity assays as well as two-generation studies can be applied for phytoestrogens to confirm their safety in long-term use. For reliable assessment of estrogenicity of dietary phytoestrogens in vivo, special emphasis should be focused on selection of the basal diet, route and doses of administration, and possible metabolic differences between the species used and humans. In conclusion, further development and standardization of the estrogenicity test methods are needed for better interpretation of both the potential benefits and risks of increasing consumption of phytoestrogens from diets and supplements.

Phytoestrogen Content of Foods Consumed in Canada, Including Isoflavones, Lignans, and Coumestan

: Phytoestrogens may play a role in hormone-related diseases such as cancer, but epidemiological and clinical data are conflicting in part due to inadequate databases used in intake estimation. A database of nine phytoestrogens in foods relevant to Western diets was developed to more accurately estimate intakes. Foods (N = 121) available in Ontario, Canada were prepared as commonly consumed and analyzed for isoflavones (genistein, daidzein, glycitein, formononetin), lignans (secoisolariciresinol, matairesinol, pinoresinol, lariciresinol), and coumestan (coumestrol) using gas chromatography-mass spectrometry methods. Data were presented on an as is (wet) basis per 100 g and per serving. Food groups with decreasing levels of total phytoestrogens per 100 g are nuts and oilseeds, soy products, cereals and breads, legumes, meat products, and other processed foods that may contain soy, vegetables, fruits, alcoholic, and nonalcoholic beverages. Soy products contain the highest amounts of isoflavone, followed by legumes, meat products and other processed foods, cereals and breads, nuts and oilseeds, vegetables, alcoholic beverages, fruits, and nonalcoholic beverages. Decreasing amounts of lignans are found in nuts and oilseeds, cereals and breads, legumes, fruits, vegetables, soy products, processed foods, alcoholic, and nonalcoholic beverages. The richest sources of specific phytoestrogens, including coumestrol, were identified. The database will improve phytoestrogen intake estimation in future epidemiological and clinical studies particularly in Western populations.

The effects of subterranean clover phytoestrogens on sheep growth, reproduction and carcass characteristics

The aim of the present study was to evaluate the effect of a prolonged administration of phytoestrogens on sheep growth rate, female reproductive response, lamb carcass conformation and meat quality. To investigate these effects, two groups of Comisana sheep (24 females and 20 males, initial average live weights of 25.0 and 29.9 kg, respectively) were fed on subterranean clover (SC, phytoestrogen content = 0.8 mg/g of DM) and Italian ryegrass (C, non-oestrogenic control diet) for about one year. Feedstuffs were offered ad libitum and supplemented with maize grain and sunflower meal to maintain an adequate and similar energy and protein intake. The results demonstrated that the prolonged administration of the selected subterranean clover cultivars, with low formononetin content (lower than 10% of total isoflavones on dry basis), did not affect ewe reproduction but induced a significant improvement in animal weigh gain and, in males, good carcass and meat characteristics.

Differential response to phytoestrogens in endocrine sensitive and resistant breast cancer cells in vitro

Women approaching menopause increasingly investigate alternatives to hormone replacement therapy. Plant phytoestrogens are being promoted as "natural" alternatives but there is a lack of substantive data to advocate their safe use in breast cancer patients receiving tamoxifen (TAM), or in those who have relapsed. The aim of our study was to investigate the proliferative effects and mode of action of the phytoestrogens genistein, daidzein and coumestrol on TAM-sensitive (-s) and resistant (-r) breast cancer cells under in vitro conditions designed to mimic the hormonal environment of the pre- and post-menopausal breast. At physiological concentrations (<10 microM) and under reduced estrogen (E2) conditions, genistein was mitogenic to TAM-s cells with TAM-r cells generally refractory. Daidzein and coumestrol were growth stimulatory irrespective of TAM sensitivity. Transcriptional activity was ERE-mediated. Combining phytoestrogens with E2 (simulating the pre-menopausal breast environment) had no effect on growth of TAM-s or TAM-r cells. Addition of 4-HT mimicked the hormonal environment in post-menopausal breast cancer patients receiving TAM. The growth inhibitory effects of 4-HT were abrogated in TAM-s cells when combined with genistein and coumestrol, and to a lesser extent, daidzein, where significant growth stimulatory effects were observed. In TAM-r cells, proliferation did not exceed control values. At phytoestrogen concentrations above 10 microM, growth inhibitory effects were seen, irrespective of estrogenic environment or cell sensitivity to TAM. Our in vitro data suggests that phytoestrogens could have potentially adverse mitogenic effects on tumour cells and should probably be avoided by patients who remain sensitive to TAM or in those with pre-existing and possibly undiagnosed breast tumours.

Effects of phytoestrogens on testosterone secretion by Leydig cells from Biłgoraj ganders ( Anser anser )

1. The aim of this study was to examine ganders at different stages of the reproductive season and the effect of: (1) diets with high phytoestrogen content and (2) in vitro phytoestrogen treatment on testosterone secretion by isolated Leydig cells. 2. Thirty-six male Biłgoraj geese were fed control diets with low phytoestrogen content (containing grass meal) and diets with high phytoestrogens (containing alfalfa meal and soy). 3. Testes were obtained from both groups of ganders at three different times of the breeding season: peak of reproductive activity (March), second half of reproductive activity (May) and beginning of photorefractoriness (July). 4. Isolated Leydig cells were incubated with LH as well as genistein, daidzein, equol and coumestrol and the concentration of testosterone in the medium was determined by radioimmunoassay. 5. The mean weight of testes from ganders in May and July decreased relative to their weights in March, but no significant differences among experimental groups were noted. 6. No differences were observed in basal and LH-stimulated testosterone secretion by Leydig cells of ganders fed the control diets and the diets with higher phytoestrogen content. In July, LH did not stimulate testosterone secretion in either group. In vitro treatment with genistein, daidzein and equol (5 and 50 µM) inhibited basal and LH-stimulated testosterone production by Leydig cells from both groups. Coumestrol (5 and 50 µM) inhibited basal testosterone secretion only in March in the control group. 7. Dietary exposure to phytoestrogens had a slight effect on in vitro testicular secretion in ganders. In vitro treatment with phytoestrogen inhibited testosterone production by Leydig cells. Genistein showed the strongest effect and coumestrol had the weakest influence on testicular secretion.

Soy Protein Infant Formulae and Follow‐On Formulae

This comment by the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Committee on Nutrition summarizes available information on the composition and use of soy protein formulae as substitutes for breastfeeding and cows' milk protein formulae as well as on their suitability and safety for supporting adequate growth and development in infants. Soy is a source of protein that is inferior to cows' milk, with a lower digestibility and bioavailability as well as a lower methionine content. For soy protein infant formulae, only protein isolates can be used, and minimum protein content required in the current European Union legislation is higher than that of cows' milk protein infant formulae (2.25 g/100 kcal vs. 1.8 g/100kcal). Soy protein formulae can be used for feeding term infants, but they have no nutritional advantage over cows' milk protein formulae and contain high concentrations of phytate, aluminum, and phytoestrogens (isoflavones), which might have untoward effects. There are no data to support the use of soy protein formulae in preterm infants. Indications for soy protein formulae include severe persistent lactose intolerance, galactosemia, and ethical considerations (e.g., vegan concepts). Soy protein formulae have no role in the prevention of allergic diseases and should not be used in infants with food allergy during the first 6 months of life. If soy protein formulae are considered for therapeutic use in food allergy after the age of 6 months because of their lower cost and better acceptance, tolerance to soy protein should first be established byclinical challenge. There is no evidence supporting the use of soy protein formulae for the prevention or management of infantile colic, regurgitation, or prolonged crying.

Phytoestrogen content of alfalfa cultivars grown in eastern Canada

AbstractAlfalfa (Medicago sativa L.) contains several phytoestrogens that may have health‐promoting effects in humans. In this study, the concentrations of three phytoestrogens (apigenin, coumestrol, and luteolin) of ten field‐grown alfalfa cultivars were determined in the seeding and post‐seeding year at two sites in Sainte‐Anne‐de‐Bellevue, QC, Canada. Herbage and phytoestrogen yield per hectare were concurrently determined. Differences between cultivars were only observed for apigenin concentration and yield and coumestrol yield. There was a 37% variation between cultivars in apigenin concentration. Site‐by‐harvest interactions and harvest main effects were observed for the concentration and yield of all three phytoestrogens. There was a 2‐ and 2.5‐fold variation in coumestrol and luteolin concentrations, respectively, between harvests of both sites. Coumestrol concentration was lower in harvests of the seeding than of the post‐seeding year. Luteolin concentration fluctuated during the five harvests at one site, but was greater in the seeding than in the post‐seeding year at the other site. There was a 5.4‐fold variation in apigenin concentration between harvests of both sites, concentrations being lower in the seeding (avg. 173 µg g−1 DM) than in the post‐seeding year. Results suggest that choice of cultivars have limited impact on alfalfa phytoestrogen concentration, which, however, greatly differ between harvests and sites. Copyright © 2006 Society of Chemical Industry

Plasma and prostate phytoestrogen concentrations in prostate cancer patients after oral phytoestogen supplementation

Phytoestrogens have been suggested to reduce the risk of prostate cancer (CaP), but no data exists on how oral phytoestrogen supplementation influences phytoestrogen concentrations in prostate tissue. Forty men with CaP, assigned for radical prostatectomy, received 240 mg of clover phytoestrogens or placebo daily for a 2-week period before their operation in a prospective and randomized study. Phytoestrogens were measured in plasma and prostate tissue by time-resolved fluoroimmunoassay (TR-FIA). All patients had low baseline phytoestrogen concentrations and only 35% had a detectable plasma concentration of equol. Oral supplementation with phytoestrogens induced a statistically significant (P<0.001) 23- and 7-fold increase in prostate tissue concentrations of the phytoestrogens genistein and daidzein, respectively. Supplemented patients demonstrated prostate tissue genistein and daidzein concentrations that were over twofold higher than their plasma. Interestingly, even though the placebo group did not receive phytoestrogen challenge, they also demonstrated twofold prostate tissue genistein and daidzein concentrations compared to their plasma values, suggesting that the prostate can concentrate available phytoestrogens. In addition, after the supplementation, 90% of the supplemented patients had a detectable plasma equol concentration. We conclude that prostate tissue can concentrate genistein and daidzein. Significant elevation of intraprostatic genistein and daidzein concentrations can be achieved with a short-term dietary phytoestrogen supplementation.

Variation in commercial rodent diets induces disparate molecular and physiological changes in the mouse uterus

Although ovarian estrogen, estradiol-17beta, is a key modulator of normal reproductive functions, natural and synthetic compounds with estrogen-like activities can further influence reproductive functions. Plant-derived phytoestrogens specifically have received much attention because of associated health benefits. However, a comprehensive understanding of the beneficial and/or detrimental impacts of phytoestrogen consumption through commercial rodent diets on uterine biology and early pregnancy at the molecular level remains largely unexplored. Using multiple approaches, we demonstrate here that exposure of adult female mice to a commercial rodent diet with higher phytoestrogen levels facilitates uterine growth in the presence or absence of ovarian estrogen, alters uterine expression of estrogen-responsive genes, and advances the timing of implantation compared with a diet with lower phytoestrogen levels. The finding that variability in phytoestrogen content in commercial rodent diets, both within and between brands, influences experimental results stresses the importance of this investigation and raises caution for investigators using rodents as animal models.

Urinary phytoestrogen concentrations in the U.S. population (1999–2000)

We report population-based urinary concentrations of phytoestrogens stratified by age, sex, and composite racial/ethnic variables. We measured the isoflavones - genistein, daidzein, equol, and O-desmethylangolensin (O-DMA) - and the lignans - enterolactone and enterodiol - in approximately 2500 urine samples from individuals aged 6 years and older who participated in the National Health and Nutrition Examination Survey (NHANES) in 1999 and 2000. We detected all phytoestrogens in over 70% of the samples analyzed; enterolactone was detected in the highest concentrations, and daidzein was detected with the highest frequency. The geometric means for each phytoestrogen were as follows: genistein, 22.3 microg/g; daidzein, 68.6 microg/g; equol, 7.65 microg/g; O-DMA, 3.95 microg/g; enterolactone, 217 microg/g; and enterodiol, 24.3 microg/g creatinine. The 95th percentiles for each phytoestrogen were as follows: genistein, 380 microg/g; daidzein, 944 microg/g; equol, 50.3 microg/g; O-DMA, 217 microg/g; enterolactone, 2240 microg/g; and enterodiol, 240 microg/g creatinine. Multivariate analyses showed statistically significant differences among many of the demographic subgroups. Adolescents had higher concentrations of genistein and equol than adults. Non-Hispanic whites had higher concentrations of enterodiol and equol than Mexican Americans or non-Hispanic blacks. Non-Hispanic whites also had higher concentrations of enterolactone and O-DMA than Mexican Americans. Mexican Americans had higher concentrations of genistein than non-Hispanic blacks; however, the opposite was found for O-DMA. Determination of phytoestrogen exposure in the US population will help us to better understand phytoestrogen consumption in the US and will assist us in elucidating the potential role of phytoestrogens in protecting against cancer and heart disease.

An international quality assurance scheme for the quantitation of daidzein and genistein in food, urine and plasma

This quality assurance (proficiency testing) scheme was commissioned to enable the Food Standards Agency (FSA) to determine the quality of analytical results submitted by researchers measuring the concentrations of phytoestrogens in foods and biological fluids in FSA-funded research projects, and also, to demonstrate that FSA-funded laboratories are producing consistent and precise results. Non-FSA-funded laboratories from around the world were also invited to join in the scheme to increase the number participants. A secondary objective was to highlight the most successful methodologies used to analyse phytoestrogens. Test materials of infant formula, plasma and urine were prepared and tested by LC-MS/MS for homogeneity to establish the concentrations of two phytoestrogens, daidzein and genistein in these test materials. Twenty one laboratories were recruited to participate in the scheme. Test materials for analysis of daidzein and genistein were issued to participants on a four-monthly basis. The results and methods of analysis were correlated and a report for each round of testing, was produced to assess the competency of laboratories. After four rounds of testing the performances of laboratories were correlated and the validity of the methods of analysis used were assessed. The performances of most laboratories for analysis of both daidzein and genistein in infant formula and biological test materials varied widely. Suitable methods that performed well for the analysis of daidzein and genistein in infant formula test materials involved a solvent extraction step, followed by reverse phase HPLC with UV detection. For biological matrices, namely plasma and urine, acceptable performance for the analysis of daidzein and genistein was achieved by methods that have an enzyme hydrolysis step before either solid phase extraction or solvent extraction and separation by either GC or HPLC and detection by MS.

Transcriptional regulation by phytoestrogens in neuronal cell lines

Widespread epidemiological data support the notion that high isoflavone intake is safe and may provide health benefits similar to estrogen. Evidence from rodents shows that certain phytoestrogens can act as estrogen receptor (ER) ligands in the brain. This study sought to determine the estrogenic profile of food-borne phytoestrogens in neuronal cell lines using physiologically attainable concentrations. At sub-micromolar concentrations genistein, daidzein, and zearalenone stimulated ERα and ERβ-dependent transcription in Neuro2A cells co-transfected with ERs and simple and complex estrogen-response-element (ERE) containing promoters, although compounds were more active in the presence of ERβ. In SN56, neuronblastoma cells expressing endogenous ERs, only genistein mimicked estrogen regulation of progesterone receptor steady state mRNA levels. Unlike pharmaceutical SERMs, phytoestrogens did not stimulate an AP-1-dependent promoter. Micromolar concentrations of phytoestrogens did not antagonize physiological estrogen concentrations or antagonist activation of an AP-1-dependent promoter. These results demonstrate that food-borne phytoestrogens, particularly those found in soy, act as ERE-, but not AP-1-dependent transcriptional activators in neurons in the absence of estrogen, and dietary levels of these compounds do not act as antagonists to physiological estrogen concentrations.

Fetal exposure to phytoestrogens—The difference in phytoestrogen status between mother and fetus

The goal of this study was to investigate fetal exposure to phytoestrogens, estrogenic compounds derived from plants, by measuring serum concentrations of phytoestrogens in maternal and cord blood. This study included 51 mothers scheduled for cesarean section (C-section), to obtain the serum of mother and fetus at almost the same time. Serum concentrations of phytoestrogens, including genistein (Gen), daidzein (Dai), coumestrol (Cou), equol (Equ; a metabolite of Dai), and sulfate-conjugated Gen, were measured in maternal and cord blood samples by LC-MS/MS and HPLC. It was found that phytoestrogens were transferred from mother to fetus. The detection rates of Gen, Dai, Equ, and Cou in cord serum were 100%, 80%, 35%, and 0%, respectively. Levels of Gen and Dai were higher in cord than in maternal serum (mean=19.4 ng/ml vs.7.2 ng/ml and 4.3 ng/ml vs.1.8 ng/ml for Gen and Dai, respectively). However, a reverse pattern was seen for Equ (cord mean=0.9 ng/ml, maternal mean=2.0 ng/ml). The correlations were significant between the concentration levels of Gen and Dai, Gen and Equ, and Gen and Dai plus Equ in cord serum. However, in maternal serum, the correlations were weak. Also, in 8 of 10 cord serum samples, sulfate-conjugated Gen was detected (mean=5.2 ng/ml, standard deviation=4.7), but it was detected from only one maternal serum (8.7 ng/ml). This study demonstrates placental transfer of phytoestrogens from mother to fetus. It is suggested that the metabolic and/or excretion rates of phytoestrogens are different between mother and fetus and once phytoestrogens are transferred to the fetus, they tend to stay in the fetal side longer than in the maternal side. While the implications for the health and development of the newborn are not known, these data suggest that the effects of fetal exposure to phytoestrogens should be studied further.

Association of Serum Phytoestrogen Concentration and Dietary Habits in a Sample Set of the JACC Study

BACKGROUND: Phytoestrogens may be associated with a reduced risk of hormone dependent neoplasms such as prostate and breast cancers. We tried to determine the validity of the association between serum phytoestrogen concentrations and dietary habits obtained from a food frequency questionnaire used in the Japan Collaborative Cohort Study (JACC Study) for Evaluation of Cancer Risk sponsored by the Ministry of Education, Science, Sports and Culture of Japan (Monbusho).METHODS: The subjects were 151 male controls who were selected for a nested case-control study for evaluating prostate cancer risk as part of the JACC Study. Dietary habits were determined using a food frequency questionnaire at baseline, and the concentrations of genistein, daidzein, and equol in frozen-stored serum samples assayed in 2002 were compared.RESULTS: Tofu intake showed a significant association with the serum concentrations of genistein and daidzein (Spearman’s correlation coefficients (rs) =0.30 and 0.27, respectively), and miso soup showed a slight association with serum concentrations of these phytoestrogens. In contrast, serum concentrations of equol were not associated with dietary intake of tofu and miso soup. After adjustment for serum daidzein concentration, serum equol concentration was associated with the intake of foods containing fat, meat, and coffee, but not green tea.CONCLUSIONS: Serum genistein and daidzein concentrations were significantly associated with dietary intake of tofu, and slightly with intake of miso soup. Consumption of fat, meat, and coffee may be associated with equol production by intestinal microflora in this sample set.

Phytoestrogens: Implications in Neurovascular Research

The early discontinuation of the Women's Health Initiative trial evaluating the effects of estrogen plus progestin due to concerns about the risk-benefit ratio of this steroid combination therapy emphasizes the need to examine alternative methods of estrogen replacement. One such alternative is isoflavone consumption of soy-derived dietary phytoestrogens that have received prevalent usage due to their ability to decrease age related disease (cardiovascular and osteoporosis), hormone-dependent cancers (breast and prostate), and peri- and postmenopausal symptoms. Differences in dietary phytoestrogen consumption result in large variations in somatic phytoestrogen content. These molecules affect estrogen and estrogen receptor function in several ways, including having both agonist and antagonist effects on estrogen receptors, as well as functioning like natural selective estrogen receptor modulators. Similar to estrogens, dietary phytoestrogens appear to affect certain aspects of vascular, neuroendocrine, and cognitive function. This article reviews health effects of estrogen, isoflavones and their hormonal mechanism of action, brain penetration by isoflavones, heath effects of isoflavones, and effects of isoflavones on vascular, neuroendocrine, and cognitive function. Because of their diverse health effects and widespread availability in soy foods, dietary phytoestrogens merit continued research into their effects on human health and cognitive function.

Determination of unusual soya and non-soya phytoestrogen sources in beer, fish products and other foods

Fish and fish products (14 samples), Indian foods and meals (10 samples), spices (30 samples) and beers (10 samples) were analysed for their phytoestrogen content, and a number of significant non-soya sources of dietary phytoestrogens were identified. No isoflavones were detected in unprocessed, farmed or ocean fish, but some samples of processed fish products contained soya isoflavones, which are assumed to come from coatings or protein addition. Additionally, some processed fish products contained, genistein glycocongugates not derived from soya. Genistein was detected in Indian meals such that, for example, a single portion of a vindalooo curry contained 11 mg genistein. The origin was most likely from the spices used, since the analysis of curry powders, chilli powder, crushed red chillies, garam masala and tandoori powder revealed that some contained genistein at more than 100 mg kg−1. Cumin was the most likely source material, although not all individual samples of cumin tested contained high levels of genistein. Prenylnaringenin phytoestrogens were determined in UK hop-based beers at mean concentrations of 0.21 mg−1 6-prenylnaringenin and 0.06 mg−1 8-prenylnaringenin. The beers also contained traces of daidzein, genistein and biochanin A. The significance of ‘hidden soya’ in processed foods and these non-soya sources of phytoestrogens is that UK dietary intake of phytoestrogens must be assumed to be higher than estimated previously and that some sources of phytoestrogens remain poorly characterized.