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Dietary Isoflavones Affect Sex Hormone-Binding Globulin Levels in Postmenopausal Women
... Therapies based on soy isoflavones (SI) are the most popular approach: these substances have been shown to alleviate climacteric symptoms at a dose of between 40 and 80 mg/day [7]. Data on SI effects show that they exert elective stimulation of β-estrogen receptors (β-ERs) with less affinity and lower potency than estrogens [7] and stimulate the synthesis of sex hormone-binding globulin (SHBG) [8]. Furthermore, the β-ERs are poorly expressed in tissues which have a higher risk for estrogen-dependent carcinoma, and thus oncological safety could be expected with long-term use [9], even if data on the subject is still lacking [10,11]. ...
The effectiveness for vasomotor symptoms and sleep disorders plus the long-term safety of a nutraceutical combination of agnus-castus and magnolia extracts combined with soy isoflavones (SI) and lactobacilli were assessed in postmenopausal women. A controlled study was carried out in menopausal women comparing this nutraceutical combination (ESP group) with a formulation containing isoflavones alone (C group) at the dosage recommended. The Kuppermann index, The Pittsburgh Sleep Quality Index (PSQI), and Short Form 36 (SF-36) were determined at baseline, three, six and 12 months. Endometrial thickness, mammary density and liver function were evaluated at baseline and after 12 months. One hundred and eighty women were enrolled in the study (100 in the ESP group and 80 in the C group). At the end of the treatment, mammary density, endometrial thickness, and hepatic function did not show substantial differences between groups. The Kuppermann index and particularly the tendency for hot flashes progressively and significantly decreased in frequency and severity during ESP versus C treatment. At the same time, a significant increase in sleep quality and psychophysical wellness parameters was observed in the ESP versus C groups. No adverse events were observed. Agnus-castus and magnolia, combined with SI + lactobacilli, can effectively and safely be used in symptomatic postmenopausal women, mainly when quality of sleep is the most disturbing complaint. The endometrium, mammary glands and liver function were unaffected after 12 months of treatment.
... Isoflavones may also cause endogenous estrogen levels to fall (42). In contrast, in postmenopausal women with low circulating estrogen, isoflavones have been shown to have a weak estrogenic effect (43). Genistein binds to the estrogen receptor with lesser affinity than estrogen itself (44). ...
... Soybean isoflavones administration might reduce hot flashes and vaginal dryness although it does not work as efficiently as estrogen replacement therapy (Vincent and Fitzpatrick, 2000). In a study with 20 post-menopausal women, soybean isoflavones were found to increase sex hormone-binding globulin (SHBG) significantly in subjects whose SHBG concentrations were in the lower end of the concentration range (Pino Ana et al., 2000). However, soybean isoflavones do not show estrogenic action on uterus of ovariectomized rat (Ishimi et al., 1999). ...
... Genistein, daidzein and their derivatives such as glucoside forms are major isoflavones in soybean. They have an estrogen-like activity that has been shown to be effective in preventing osteoporosis 19 , in controlling and preventing cancer 10,13 , in lowering total and LDL cholesterol 12 and also have some benefits in the postmenopausal hormone replacement therapy 5,18 . Dominant oligosaccharides of soybean are sucrose, raffinose and stachyose. ...
Aiming to select suitable strains of lactic acid bacteria for producing yogurt-like functional food from soybean milk, the fermentation properties of 14 lactic acid bacterial strains belonging to genera Bifido-bacterium, Lactobacillus, Lactococcus and Streptococcus were evaluated using soybean milk as the culture medium. All 14 strains examined were able to grow in soybean milk. Twelve out of the 14 strains lowered the pH of the medium and produced lactic acid. Tested strains showed a variety of con-sumption patterns of oligosaccharides and hydrolyzing capacity of isoflavone glucosides. Three strains, Bifidobacterium breve JCM 1192, B. bifidum JCM 1255 and Lb. casei subsp. rhamnosus IFO 3425 exhibited the most promising results. These strains could hydrolyze both daidzin and genistin to corresponding aglycones, and consume raffinose and stachyose in addition to lowering the pH and pro-ducing lactic acid.
... This finding is of interest since ERb has a higher level of expression than that of ERa in brain regions critical to memory function and which are vulnerable to AD, such as the basal forebrain, hippocampus, and cerebral cortex. Other potential mechanisms of phytoestrogen action is through tyrosine kinase inhibition, DNA topoisomerase inhibition, inhibition of aromatase function, stimulation of sex-hormone-binding globulin in the liver thereby reducing free, biologically active estradiol in the plasma and by inducing antioxidant properties [Adlercreutz et al., 1993; Monti and Sinha, 1994; Kulling and Metzler, 1997; Pino et al., 2000]. Because of their mixed agonist/antagonist estrogen receptor profile, phytoestrogens have received considerable attention as potential alternatives to estrogen. ...
Estrogen regulation of cognitive function and prevention of neurodegenerative disease has come to be of major scientific and clinical importance. While these functions rank paramount among concerns of women during menopause, the neoplastic risks associated with estrogen and hormone replacement therapy lead most women to elect against hormone intervention during menopause or to seek alternative estrogens in an attempt to ameliorate menopause-associated deficits and disease risks. Development of an effective selective estrogen receptor modulator (SERM) for use as an alternative to hormone replacement therapy must address the issues of efficacy in and availability to the brain. Abrief review of estrogen effects on cognition, neuroprotective capability, and disease prevention is provided followed by an analysis of current knowledge regarding SERM efficacy in brain. Lastly, the challenges that remain for developing an effective NeuroSERM™ are considered. Drug Dev. Res. 56:380–392, 2002. © 2002 Wiley-Liss, Inc.
Continuing research is being conducted on novel preventive and therapeutic drugs for cardiovascular diseases (CVDs). Daidzein has shown potential beneficial effects regarding various CVDs and risk factors. However, data in this regard are inconsistent, and there is an urge to accumulate. Therefore, we reviewed the effects of daidzein and daidzin on CVDs. We conducted a search through Scopus, PubMed, Google Scholar, and Web of Science from inception up to October 2023 to find studies with the primary intention of assessing the impacts of daidzein and daidzin on cardiovascular disease in various in vitro, animal, and clinical settings. In vitro and animal studies showed that daidzein and daidzin are effective in terms of reducing inflammation, oxidative stress, hyperlipidemia, myocardial infarction, thromboembolism, hypertension, and aneurysms. However, clinical studies only confirmed a relatively small portion of the previous findings of the in vitro and animal investigations, including anti‐hyperlipidemic effects. In conclusion, in vitro and animal studies have reported potential therapeutic effects for daidzein and daidzin regarding CVDs. However, most of the clinical studies were unable to exhibit the same results. Hence, further clinical studies are required to determine the outcomes of administering daidzein and its derivatives for an extended period and in various doses.
This chapter begins with an overview of the extent to which endocrine-disrupting chemicals (EDCs) can enter human tissues from environmental exposure. Retention of EDCs in body tissues may be influenced both by their route of entry and by their resistance to physiological clearance processes. Their endocrine-disrupting activity and biological availability may also be influenced by endogenous metabolic reactions. Measurements using a range of body tissues have demonstrated the ubiquitous distribution of many EDCs across the human population, but the source of the body burden is difficult to establish due to the widespread use of these compounds. The measurement of so many different EDCs in human tissues demonstrates the potential for mixtures of EDCs at low doses to interfere in the long term on hormone regulation with adverse consequences for human health. Many different nonlinear, nonmonotonic dose responses to EDCs have been demonstrated, and effects at high doses may not always be predictive of effects at low doses. The effects of EDCs vary in different tissues and between individuals, but timing is also important. Critical windows of susceptibility to EDC exposure exist during prenatal life and early childhood, and some exposures to EDCs in utero can produce long-lasting effects into adult life and onto future generations.
Xenoestrogens and phytoestrogens are referred to as “foreign estrogens” that are produced outside of the human body and have been shown to exert estrogen-like activity. Xenoestrogens are synthetic industrial chemicals, whereas phytoestrogens are chemicals present in the plant. Considering that these environmental estrogen mimics potentially promote hormone-related cancers, an understanding of how they interact with estrogenic pathways in human cells is crucial to resolve their possible impacts in cancer. Here, we conducted an extensive literature evaluation on the origins of these chemicals, emerging research techniques, updated molecular mechanisms, and ongoing clinical studies of estrogen mimics in human cancers. In this review, we describe new applications of patient-derived xenograft (PDX) models and single-cell RNA sequencing (scRNA-seq) techniques in shaping the current knowledge. At the molecular and cellular levels, we provide comprehensive and up-to-date insights into the mechanism of xenoestrogens and phytoestrogens in modulating the hallmarks of cancer. At the systemic level, we bring the emerging concept of window of susceptibility (WOS) into focus. WOS is the critical timing during the female lifespan that includes the prenatal, pubertal, pregnancy, and menopausal transition periods, during which the mammary glands are more sensitive to environmental exposures. Lastly, we reviewed 18 clinical trials on the application of phytoestrogens in the prevention or treatment of different cancers, conducted from 2002 to the present, and provide evidence-based perspectives on the clinical applications of phytoestrogens in cancers. Further research with carefully thought-through concepts and advanced methods on environmental estrogens will help to improve understanding for the identification of environmental influences, as well as provide novel mechanisms to guide the development of prevention and therapeutic approaches for human cancers.
Introduction
Menopausal complaints are a critical aspect of women’s lives. In particular vasomotor symptoms, such as hot flashes, may seriously impact quality of life and are considered the most bothersome complaint by patients. Although Menopausal Hormone Therapy (MHT) is considered the best option, women increasingly ask for a natural and more tailored treatment approach.
Areas covered
Nutraceutical compounds represent the most widespread alternative therapy for vasomotor symptoms, and their use is somewhat increasing. In this review, the authors analyzed the mechanism of action and the related safety of non-hormonal treatments, including new approaches and future aspects.
Expert opinion
MHT represents the traditional therapy for menopausal complaints, especially for severe and moderate symptoms; however, evidence has not defined a safety profile for all patients. To address this issue, nutraceuticals could represent a compelling and useful non-hormonal approach in selected patients.
Isoflavones are phytoestrogen compounds with important biological activities, including improvement of cardiovascular health. This activity is most evident in populations with a high isoflavone dietary intake, essentially from soybean-based products. The major isoflavones known to display the most important cardiovascular effects are genistein, daidzein, glycitein, formononetin, and biochanin A, although the closely related metabolite equol is also relevant. Most clinical studies have been focused on the impact of dietary intake or supplementation with mixtures of compounds, with only a few addressing the effect of isolated compounds. This paper reviews the main actions of isolated isoflavones on the vasculature, with particular focus given to their effect on the determinants of blood pressure regulation. Isoflavones exert vasorelaxation due to a multitude of pathways in different vascular beds. They can act in the endothelium to potentiate the release of NO and endothelium-derived hyperpolarization factors. In the vascular smooth muscle, isoflavones modulate calcium and potassium channels, leading to hyperpolarization and relaxation. Some of these effects are influenced by the binding of isoflavones to estrogen receptors and to the inhibition of specific kinase enzymes. The vasorelaxation effects of isoflavones are mostly obtained with plasma concentrations in the micromolar range, which are only attained through supplementation. This paper highlights isolated isoflavones as potentially suitable alternatives to soy-based foodstuffs and supplements and which could enlarge the current therapeutic arsenal. Nonetheless, more studies are needed to better establish their safety profile and elect the most useful applications
The health‐promoting benefits of medicine and food homology (MFH) are known for thousands of years in China. However, active compounds and biological mechanisms are unclear, greatly limiting clinical practice of MFH. The advent of gut microbiota analysis and metabolomics emerge as key tools to discover functional compounds, therapeutic targets, and mechanisms of benefits of MFH. Such studies hold great promise to promote and optimize functional efficacy and development of MFH‐based products, for example, foods for daily dietary supplements or for special medical purposes. In this review, we summarized pharmacological effects of 109 species of MFH approved by the Health and Fitness Commission in 2015. Recent studies applying genome sequencing of gut microbiota and metabolomics to explain the activity of MFH in prevention and management of health consequences were extensively reviewed. We discussed the potentiality in future to decipher functional activities of MFH by applying metabolomics‐based polypharmacokinetic strategy and multiomics technologies. The needs for personalized MFH recommendations and comprehensive databases have also been highlighted. This review emphasizes current achievements and challenges of the analysis of gut microbiota and metabolomics as a new avenue to understand MFH. Application of genome sequencing of gut microbiota and metabolomics to decipher functional activities of medicine and food homology and explore underlying mechanisms of benefits of medicine and food homology on health consequences.
Dietary phytoestrogens are bioactive compounds with estrogenic activity. With the growing popularity of plant-based diets, the intake of phytoestrogen-rich legumes (especially soy) and legume-derived foods has increased. Evidence from preclinical studies suggests these compounds may have an effect on hormones and health, although the results of human trials are unclear. The effects of dietary phytoestrogens depend on the exposure (phytoestrogen type, matrix, concentration, and bioavailability), ethnicity, hormone levels (related to age, sex, and physiological condition), and health status of the consumer. In this review, we have summarized the results of human studies on dietary phytoestrogens with the aim of assessing the possible hormone-dependent outcomes and health effects of their consumption throughout a lifespan, focusing on pregnancy, childhood, adulthood, and the premenopausal and postmenopausal stages. In pregnant women, an improvement of insulin metabolism has been reported in only one study. Sex hormone alterations have been found in the late stages of childhood, and goitrogenic effects in children with hypothyroidism. In premenopausal and postmenopausal women, the reported impacts on hormones are inconsistent, although beneficial goitrogenic effects and improved glycemic control and cardiovascular risk markers have been described in postmenopausal individuals. In adult men, different authors report goitrogenic effects and a reduction of insulin in non-alcoholic fatty liver patients. Further carefully designed studies are warranted to better elucidate the impact of phytoestrogen consumption on the endocrine system at different life stages.
There is ample evidence that the Mediterranean diet reduces breast cancer risk, despite the fact that evidence across studies and populations has not been consistent. The protective effect of the Mediterranean diet is in line with the fact that some of its key components, such as fruit, vegetables, folate, and olive oil, have also been shown to have beneficial effects with regard to breast carcinogenesis.
The mechanisms through which these components are hypothesized to exert their protective effects include epigenetics and more specifically DNA methylation; antioxidant functions; biological response modification; and antiestrogenic, antiproliferative, and antiangiogenic activities. Additionally, nutrigenetics and metabolomics studies on the association between Mediterranean diet adherence and breast cancer further support the protective effects of this dietary pattern.
Further research to investigate the effects of intensity and timing of exposure and to elucidate the mechanistic pathways involved in the relationship is essential. The answers to these questions will provide biomarkers for prevention and early detection and targets for therapy, establishing the causality of the association and supporting adherence to the Mediterranean diet as a prevention strategy for breast cancer.
This chapter examines the evidence for sex-specific dietary recommendations for the prevention and treatment of the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) in women. Women with the MetS are at an increased risk for developing T2DM [1,2], so rather than discussing all forms of diabetes, we have chosen to focus in particular on T2DM. A central feature of the MetS, which has also been linked to increased incidence of T2DM, is abdominal obesity. While this is briefly discussed in the section on the etiology of the MetS and T2DM, it was not the purpose of this chapter to review the literature on women, nutrition, and abdominal obesity. The reader is referred to Chapter 7 for this discussion. This chapter discusses present nutrition knowledge pertaining to the MetS and T2DM, with an emphasis on findings relevant to women.
Abstract
Ethnopharmacological relevance
Research in the past half a century has gradually sketched the biological mechanism leading to androgenetic alopecia (AGA). Until recently the aetiological paradigm has been too limited to enable intelligent commentary on the use of folk remedies to treat or reduce the expression of this condition. However, our understanding is now at a point where we can describe how some folk remedies work, predict how effective they will be or why they fail.
Results
The new paradigm of AGA is that inheritance and androgens (dihydrotestosterone) are the primary contributors and a secondary pathology, microinflammation, reinforces the process at more advanced stages of follicular miniaturisation. The main protagonist to microinflammation is believed to be microbial or Demodex over-colonization of the infundibulum of the pilosebaceous unit, which can be ameliorated by antimicrobial/acaricidal or anti-inflammatory therapies that are used as adjuvants to androgen dependent treatments (either synthetic or natural). Furthermore, studies reveal that suboptimal androgen metabolism occurs in both AGA and insulin resistance (low SHBG or high DHT), suggesting comorbidity. Both can be ameliorated by dietary phytochemicals, such as specific classes of phenols (isoflavones, phenolic methoxy abietanes, hydroxylated anthraquinones) or polycyclic triterpenes (sterols, lupanes), by dual inhibition of key enzymes in AGA (5α-reductase) and insulin resistance (ie., DPP-4 or PTP1B) or agonism of nuclear receptors (PPARγ). Evidence strongly indicates that some plant-based folk remedies can ameliorate both primary and secondary aetiological factors in AGA and improve insulin resistance, or act merely as successful adjuvants to mainstream androgen dependent therapies.
Conclusion
Thus, if AGA is viewed as an outcome of primary and secondary factors, then it is better that a ‘multimodal’ or ‘umbrella’ approach, to achieve cessation and/or reversal, is put into practice, using complementation of chemical species (isoflavones, anthraquinones, procyanidins, triterpenes, saponins and hydrogen sulphide prodrugs), thereby targeting multiple ‘factors’.
Soy and soy-based foods are considered healthy, particularly in many Asia–Pacific countries, where soy products have long been consumed. Soy and soy-related products have been found to help prevent the occurrence of cardiovascular diseases and certain types of cancer, such as breast and prostate cancer. These products can also have antioxidative effects that alleviate hot flashes during menopause and bone loss. These biological and therapeutic functions are primarily due to the isoflavones derived from soy, whose structure is similar to the structure of 17-β-oestradiol. Despite the many health benefits for humans and animals, the application of isoflavones remains controversial because of their anti-oestrogenic properties. We focused on general information regarding isoflavones, as well as their structure, function, and application. We summarized evidence showing that dietary or supplemental isoflavones exert protective effects on the health of humans and animals. Based on the literature, we conclude that soy foods and isoflavones may be effective and safe; however, more high-quality trials are needed to fully substantiate their potential use.
A wide range of health benefits have been ascribed to soya intake including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms. Because it is a hormonally active diet, however, soya can also be endocrine disrupting, suggesting that intake has the potential to cause adverse health effects in certain circumstances, particularly when exposure occurs during development. Consequently, the question of whether or not soya phyto-oestrogens are beneficial or harmful to human health is neither straightforward nor universally applicable to all groups. Possible benefits and risks depend on age, health status, and even the presence or absence of specific gut microflora. As global consumption increases, greater awareness and consideration of the endocrine-disrupting properties of soya by nutrition specialists and other health practitioners is needed. Consumption by infants and small children is of particular concern because their hormone-sensitive organs, including the brain and reproductive system, are still undergoing sexual differentiation and maturation. Thus, their susceptibility to the endocrine-disrupting activities of soya phyto-oestrogens may be especially high. As oestrogen receptor partial agonists with molecular and cellular properties similar to anthropogenic endocrine disruptors such as bisphenol A, the soya phyto-oestrogens provide an interesting model for how attitudes about what is 'synthetic' v. what is 'natural,' shapes understanding and perception of what it means for a compound to be endocrine disrupting and/or potentially harmful. This review describes the endocrine-disrupting properties of soya phyto-oestrogens with a focus on neuroendocrine development and behaviour.
Endogenous estrogen levels are strongly associated with breast cancer risk, but its determinants are not well understood. We conducted a cross-sectional study of 144 healthy postmenopausal women, participants in a population-based prospective investigation of diet and cancer risk among Chinese in Singapore. The relationships between plasma levels of estrone (E-1), estradiol (E-2), and androstenedione and dietary intake of soy and other food groups were investigated. Data on diet and other lifestyle factors were obtained from a structured questionnaire with a validated dietary component that was administered in-person to all participants. Few dietary factors emerged as determinants of plasma estrogen levels in this population. An exception was soy, which was significantly associated with plasma E-1 levels. Specifically, E-1 levels were 15% lower among individuals in the highest quartile of soy protein intake compared with those in the lower three quartiles of intake (P = 0.047). E-1 levels did not differ between individuals in the lower three quartiles of soy protein intake. Similar patterns of differences in E-1 levels emerged in analyses by intake of isoflavones and total soy products. These findings on soy were independent of the four nondletary factors (see below) that significantly influenced estrogen levels. Both E-1 and E-2 levels increased with high body mass index [BMI (weight/height2)]; the respective levels were 41% (twosided P = 0.02) and 17% higher (P = 0.34) among women in the highest BMI category (BMI greater than or equal to 24) compared with those in the lowest category (BMI < 20). After adjustment for BMI and age, women with a late age at menarche (age 17 years or older) showed significantly lower E-1 (30% lower; P = 0.02) and E-2 levels (24% lower; P = 0.02) compared with women with earlier age at menarche (before age 17 years) and who were nulliparous or had a late age at first live birth (after age 31 years). Current smokers showed significantly higher E-2 levels (28%) than nonsmokers (P = 0.04). These findings are discussed in relation to the recent doubling of breast cancer incidence among Chinese women in Singapore.
Breast cancer incidence is higher in Western countries than in Asian countries. In addition, migrant populations from Asia to the United States have increased incidence of breast cancer ¹ (Figure 3.1). As for Japan, breast cancer mortality is higher in metropolitan areas but shows steadily increasing trends for all prefectures² (Figure 3.2). This evidence suggests that the difference in life-style between the Western countries and Asia, in particular, the difference in eating habits, may be associated with the difference in incidence of breast cancer. Attention has been paid to soybean products since they are widely consumed in Asia but rarely consumed in Western countries (at least until quite recently). There is a 10- to 100-fold difference in consumption between Japan and the Western countries (Table 3.1). ³⁻¹³.
Human diet contains a series of bioactive vegetal compounds that can improve human health. Among these, there has been a special interest for phytoestrogens. This article reviews the evidence about the potential benefits of phytoestrogens for human health. Forty eight manuscripts were selected for their study design and relevance to human health. The cell growth inhibitory effects of phytoestrogens and their implication in breast cancer are reviewed. Also the effects of these compounds on serum lipid levels and the effectiveness of a phytoestrogen derivate, ipriflavone, on the prevention of osteoporosis are analyzed. Although these compounds have a great potential for improving health, there is still not enough evidence to recommend the routine use of phytoestrogens.
Purpose: The objective of this prospective 6-months open observational study was to investigate the influence of soy-isoflavones and selected micronutrients on typical symptoms in peri- and postmenopausal women. Patients and Methods: 29 peri- (regular or unregular bleedings < 12 mo.) and postmenopausal (no bleedings > 12 mo.) women with menopausal symptoms measured by Menopause Rating Scale (MRS) II received an oral supplement containing 50mg soy-isoflavones, 240 mg calcium, 60 mg magnesium, 90 mg vitamin C and 30 mg vitamin E, α-Linolenic acid 630 mg (Salus Novasoy® capsules of the concern Salushaus, Bruckmühl). The following data were collected at baseline and after 4, 12 and 26 weeks: MRS II, date of the last menstruation, FSH, LH, DHEAS, testosterone, estradiol, estrone, progesterone, prolactin, TSH, ALT, AST, triglycerides, cholesterol, HDL, homocystein und lipoprotein (a), haemogram, weight, blood pressure, tolerability by scale from 1-4 ("very good" - "bad"), side effects by numeration; endometrial sonography and vaginal smear were performed at baseline and in week 12 and 26. Data were analyzed by Wilcoxon rank sum tests. Results: Data of 24 study participants between 42 and 61 years (median 52 years) over 6 months were analyzed. At the beginning the median of MRS II scores was 15 (range 3-29). Significant reduction of menopausal symptoms in the MRS-score after 26 weeks treatment in 16 of 24 patients was observed (reduction of 3,5 points at week 26 [p = 0.004]). Triglycerides and cholester ol were reduced in week 12 (p = 0.001 and p = 0.02, respectively). Significant increase of testosterone (p = 0.006) in week 26. No change of other parameters, no effect on the vaginal or endometrial mucosa was observed. "Good" or "very good" tolerability was reported by all 24 patients. Minor, possibly treatment-related temporary side effects were noted in six patients. Conclusion: Peri- and postmenopausal women seeking an alternative solution to Hormone Replacement Therapy could possibly benefit from treatment with soy-isoflavones in regard to menopausal symptoms and lipids. Randomized, double blind, placebocontrolled trials are warranted to further characterize effect profile, long-term preventive potential and side-effects of phytoestrogens in relation to climacteric symptomes, bone turnover, cardio-vascular system, breast and endometrium.
There is ample evidence that the Mediterranean diet reduces breast cancer risk, despite the fact that findings across studies and populations have not been consistent. The protective effect of the Mediterranean diet is in line with the fact that some of its key components, such as fruit, vegetables, folate, and olive oil, have also been shown to have beneficial effects with regards to breast carcinogenesis.The mechanisms through which these components are hypothesized to exert their protective effects include epigenetics and more specifically DNA methylation, antioxidant functions, biological response modification, antiestrogenic, antiproliferative, and antiangiogenic activities.Further research to investigate the effects of intensity and timing of exposure and to elucidate the mechanistic pathways involved in the relationship is essential. The answers to these questions will provide biomarkers for prevention and early detection as well as targets for therapy, establishing the causality of the association and supporting adherence to the Mediterranean diet as a prevention strategy for breast cancer.
This chapter begins with an overview of the extent to which endocrine-disrupting chemicals (EDCs) can enter human tissues from environmental exposure. Retention of EDCs in body tissues may be influenced both by their route of entry and by their resistance to physiological clearance processes. Their endocrine-disrupting activity and biological availability may also be influenced by endogenous metabolic reactions. Measurements using a range of body tissues have demonstrated the ubiquitous distribution of many EDCs across the human population, but the source of the body burden is difficult to establish due to the widespread use of these compounds. The measurement of so many different EDCs in human tissues demonstrates the potential for mixtures of EDCs at low doses to interfere in the long term on hormone regulation with adverse consequences for human health. Many different nonlinear, nonmonotonic dose-responses to EDCs have been demonstrated, and effects at high doses may not always be predictive of effects at low doses. The effects of EDCs vary in different tissues and between individuals, but timing is also important. Critical windows of susceptibility to EDC exposure exist during pre-natal life and early childhood, and some exposures to EDCs in utero can produce long-lasting effects into adult life and on future generations.
Depending on nutritional habits, our diet may contain a substantial load of phenolics, defined as plant secondary metabolites consisting of one to several phenol groups. Their bioavailability, in other words the active fraction of ingested amounts that reaches targeted cell types or tissues where biochemical properties can act, is markedly influenced by metabolism and absorption in the gastrointestinal tract. Indeed, our intestine is the primary metabolically active site of absorption of exogenous factors in our body and harbors trillions of microbial cells with a vast metabolic potential, referred to as the intestinal microbiota. The aim of the present book chapter is to give insights into the role of phenolic compounds in human health. We will focus our attention on two families of polyphenols of importance in human nutrition, namely, the isoflavones and lignans, and will discuss in detail the role of intestinal microorganisms in regulating their metabolism and thereby health effects.
Objective:
Several studies have demonstrated that soy isoflavone (SIF) supplementation can improve aspects of cognitive function. However, these findings remain controversial. We aimed to quantify the effects of SIF supplementation on improving cognitive function in postmenopausal women.
Methods:
Databases and relevant Websites were searched for relevant studies up to March 2014. Two reviewers independently verified all potentially suitable randomized controlled trials (RCTs) using inclusion and exclusion criteria, and the quality of identified RCTs was assessed using the Jadad scale and the Risk of Bias Tool from the "Cochrane handbook for systematic reviews of interventions." Any disagreement on study quality or data extraction was resolved by consensus; a third reviewer was consulted if needed. Standardized mean differences (SMDs) in cognitive function test scores were calculated between SIF-treated and placebo-treated groups.
Results:
We conducted a meta-analysis of 10 placebo-controlled RCTs of SIF supplementation (1,024 participants; treatment duration of 6 wk to 30 mo). The overall SMD in summary cognitive function test scores (0.08) was statistically significant (95% CI, 0.02-0.15; P = 0.014). The summary SMD for visual memory (0.10) was statistically significant (95% CI, 0.02-0.18; P = 0.016). In subgroup analyses, the statistically significant SMDs were as follows: 0.12 (95% CI, 0-0.25; P = 0.044) for non-US countries; 0.16 (95% CI, 0.05-0.28; P = 0.004) for mean age younger than 60 years; and 0.15 (95% CI, 0.03-0.27; P = 0.011) for treatment duration less than 12 months.
Conclusions:
SIF supplementation seems to have a positive effect on improving summary cognitive function and visual memory in postmenopausal women. There may be a critical window of opportunity in initiating SIF use at an earlier age in postmenopausal women, and geography and treatment duration seem to be factors influencing the effects of SIF supplementation. All individuals in the included studies should be followed up to observe the incidence rates of Alzheimer's disease and dementia, and future studies should report any adverse effects of SIF supplementation.
Seoritae is a type of black soybean that is known to have health-promoting effects due to its high isoflavone and anthocyanin contents. We evaluated whether Seoritae extract (SE) had beneficial effects on the reduction of prostate weight in a rat model of benign prostatic hyperplasia (BPH). BPH was induced by intramuscular injections of testosterone enanthate once a week for 5 weeks in Sprague-Dawley rats, and rats were treated with or without daily oral doses of SE during BPH induction. After 5 weeks, the oxidative stress (superoxide dismutase and 8-hydroxy-2-deoxyguanosine), apoptosis (caspase-3), and activity of 5-alpha reductase were evaluated in the serum and prostate. The SE treatment group showed a significant decrease in prostate weight, oxidative stress, apoptosis, and 5-alpha reductase activity compared to the nontreated BPH group. These results show that SE is effective in decreasing the weight and proliferation of the prostate, and suggest that SE may be an effective treatment for BPH.
Soybeans contain several putative anticarcinogens. To determine which anticarcinogen is most likely responsible for the hypothesized anticancer effects of soy specifically in regard to breast and prostate cancer, Japanese dietary data and findings from epidemiologic studies were first used to estimate the amount of soy associated with anticancer effects. On the basis of this information, the experimental data for likely candidates were evaluated. One hundred g of tofu was selected as a basis for estimating the contribution of soy to the total Japanese dietary intake of the various anticarcinogens in soybeans. Data suggest that tofu contributes only minor amounts of phenolic acids (<1%), phytosterols (<5%), and vitamin E (∼10%), modest amounts of protein (10-13%), omega-3 fatty acids (∼15%), and phytate (∼20%), but large amounts of saponins (∼80%), the Bowman-Birk Inhibitor (BBI) (∼90%), and isoflavones (100%). The evidence that saponins inhibit breast and prostate cancer risk is unimpressive. The BBI clearly has exciting potential as a chemopreventive agent but data specifically for breast and prostate cancer are not strong. In contrast, several lines of evidence suggest isoflavones reduce breast (primarily via early exposure) and prostate cancer risk. Thus, if soy consumption reduces cancer risk, protective effects are likely due solely to isoflavones. However, this conclusion does not preclude the possibility that other soybean anticarcinogens, when consumed in amounts greater than that found in 100 g tofu, exert anticancer effects in humans.
Human diet contains a series of bioactive vegetal compounds that can improve human health. Among these, there has been a special interest for phytoestrogens. This article reviews the evidence about the potential benefits of phytoestrogens for human health. Forty eight manuscripts were selected for their study design and relevance to human health. The cell growth inhibitory effects of phytoestrogens and their implication in breast cancer are reviewed. Also the effects of these compounds on serum lipid levels and the effectiveness of a phytoestrogen derivate, ipriflavone, on the prevention of osteoporosis are analyzed. Although these compounds have a great potential for improving health, there is still not enough evidence to recommend the routine use of phytoestrogens (Rev Méd Chile 2003; 131: 1321-28). (Key Words: Breast neoplasms; Isoflavones; Lipids and antilipemic agents; Phytoestrogen) Recibido el 24 de abril, 2003. Aceptado en versión corregida el 8 de septiembre, 2003. Financiamiento: FONDECYT # 1000946.
Isoflavone in soybean and its products have numerous beneficial health effects. A number of clinical studies have demonstrated that dietary soy isoflavone can relieve menopausal symptoms, lower risks of breast cancer, and lower cholesterol and glucose. Among the various effects of isoflavone, the role of cholesterol and glucose reduction seems to be well documented; however, other effects such as reproductive hormones were inconclusive and inconsistent. The main objective of the present study was to investigate the effects of six-month dietary traditional fermented soybean intake on BMI, reproductive hormones, lipids, and glucose among postmenopausal women. Subjects were women with their last menstrual period occurring at least 12 months prior to selection by interview and health screening from Baan Tham Village, Phayao Province, Thailand. A total of 60 women were divided into 2 groups: experimental group (n=31) and reference group (n=29). The experimental group was permitted to continue their usual diet, and supplemented with fermented soybean for 6 months. The fermented soybean provided approximately 60 mg of isoflavone per day. The remarkable findings were that dietary fermented soybean had favorable effects on progesterone and cholesterol, but had no effects on estradiol, glucose, and triglycerides. Although estradiol and glucose in the experimental group did not change, a decrease of estradiol and an increase of glucose were found in the reference group. Our results, therefore, suggest that fermented soybean may have beneficial effects on reproductive hormones and cholesterol, and they would be warrant further detail investigations.
One of the most important environmental factors to promote epigenetic alterations in an individual is nutrition and exposure to plant compounds. Phytoestrogens and other phytochemicals have dramatic effects on cellular signaling events, so have the capacity to dramatically alter developmental and physiological events. Epigenetics provides one of the more critical molecular mechanisms for environmental factors such as phytoestrogens/phytochemicals to influence biology. In the event these epigenetic mechanisms become heritable through epigenetic transgenerational mechanisms the impacts on the health of future generations and areas such as evolutionary biology need to be considered. The current review focuses on available information on the environmental epigenetics of phytoestrogen/phytochemical exposures, with impacts on health, disease and evolutionary biology considered.
Objective:
To assess the safety of a nutraceutical compound containing soy isoflavones and Lactobacillus sporogenes on endometrium, breast and liver function.
Setting:
Outpatient Menopausal Clinic.
Study design:
130 healthy postmenopausal women suffering from menopausal symptoms were randomized to receive soy isoflavones 60 mg and Lactobacillus sporogenes 1 billion spores (group E: 65 women) or calcium and vitamin D₃ (group C: 65 women). Safety of the treatment was assessed at baseline and after 1 year taking into account endometrial thickness, mammographic density, serum levels of transaminases, γ-GT and bilirubin. Efficacy of the treatment was evaluated rating the score of menopausal symptoms at baseline and every 3 months. The statistical analysis was carried out with χ², Fisher exact's test and ANOVA.
Results:
After 12 months of treatment mammographic density, endometrial thickness and hepatic function did not show significant differences between groups, while menopausal symptoms were progressively and significantly reduced in severity and frequency during treatment with soy isoflavones plus Lactobacillus sporogenes versus calcium plus vitamin D₃.
Conclusion:
A 12 months treatment with a nutraceutical compound based on isoflavones and Lactobacillus sporogenes at the recommended doses is safe for endometrium, mammary glands and liver function in postmenopausal women.
Key Points
Soybeans contain several potential anticancer components.
Epidemiological studies suggest that consumption of soy foods is associated with lower risk of breast and prostate cancer.
The epidemiological evidence for the association of soy food consumption and reduced risk of other cancers is not consistent.
Animal studies generally support the conclusion that some components in soy prevent the development and progression of breast, prostate, and colorectal cancers.
In animal studies, it appears that soy may act synergistically with bioactive components from other foods (e.g., tea) to reduce breast and prostate cancer.
There are several possible mechanisms by which soy bioactives may reduce cancer risk.
1. Current cancer models comprise those that are inherited through the germline and represent only ~5% of total cases of human cancers. These tumors originate because of mutational events. The remaining ~95% originate as sporadic events and evolve as a result of exposure to the environment, which includes exposure to both environmental contaminants and dietary agents.
2. The multistage model of carcinogenesis identifies various phases, initiation, promotion, and progression, which determine the evolution of normal somatic cells to heterogeneous populations with cancer potential. This process appears to be influenced by tissue microenvironment and organization. Significant opportunities in nutrition and cancer prevention exist in the early stages of initiation and promotion prior to clonal expansion of heterogeneous populations. Targeting initiators, cocarcinogens, and promoters may provide the best opportunity in cancer prevention since the majority of advanced solid tumors are resistant to therapy.
3. Nutrigenomics represents a strategy that can be applied to the study and prevention of many diseases including cancer. It has been defined as a pyramidal approach that encompasses the study of molecular relationships between nutrients and genes (nutrigenetics), how these interactions influence changes in the profile of transcripts (transcriptomics), proteins (proteomics), and metabolites (metabolomics). DNA methylation and histone modifications are epigenetic events that mediate heritable changes in gene expression and chromatin organization in the absence of changes in the DNA sequence. The age-increased susceptibility to cancer may derive from accumulation of epigenetic changes and represents a potential target for therapies with bioactive compounds.
4. Factors that mediate the response to dietary factors include nuclear receptors and transcription factors, which function as sensors to dietary components and determine changes in the profile of transcripts.
5. Integration of high-throughput proteomic and metabolomic approaches with computational techniques is necessary to understand the complexity of the biological response to specific bioactive compounds or associations of nutrients and identify key molecular targets in cancer prevention and treatment.
Dietary supplements used by women during menopause are usually based on plant extracts containing isoflavonoids, daidzein and genistein. Genistein is a known inhibitor of many enzymes, including thyroid peroxidase (TPO). In the thyroid follicle, genistein acts as its alternate substrate for the formation of genistein iodinated derivatives. The aim of this study was to search for daidzein- and genistein-iodinated derivatives in urine of isoflavonoid-supplemented women. Additionally, selected phytoestrogens, steroid and thyroid hormones before and after three months of phytoestrogen supplementation were estimated. Urinary levels of free phytoestrogen increased significantly after therapy. They ranged between 0.3-1600, 0.6-670 and 0-206 nmol/L for daidzein, genistein and S-equol, respectively. Monoiodinated derivatives of genistein were observed (0-504 pmol/L) in 60% of the investigated samples. Steroid and thyroid hormone levels were within the normal range and were not significantly altered. The presence of monoiodinated derivates in human urine confirmed that genistein and daidzein may enter human thyroid follicles and influence TPO. Since the levels of the free thyroid hormones were not affected, we propose that the use of phytoestrogen dietary supplements is not associated with the development of thyroid-gland disorders in subjects with adequate iodine intake.
Isoflavones, a group of phytoestrogens, are selective oestrogen receptor (ER) modulators. They may positively impact endocrine-related conditions but the current evidence is sparse. Equol, a non-steroidal oestrogen, is produced by the metabolism of the isoflavone daidzein by intestinal bacteria. In Western countries, 30-50% of individuals metabolize daidzein into equol and are known as equol producers. Equol production may be the source of benefit from isoflavones in endocrine disease.
Estrogen therapy is, to date, the most effective treatment of menopausal syndrome and also has a favorable effect on lipid profiles. Because of its potential adverse effects, however, a more acceptable alternative therapy needs to be identified. This study examines the effect of soy germ isoflavones on menopausal symptoms and serum lipids.
Ninety early postmenopausal Chinese women, aged 45 to 60 years, were randomly assigned to three treatment groups (30 each) receiving daily doses of 0 (placebo), 84, and 126 mg of soy germ isoflavones. Hot flush frequency, Kupperman scores, serum 17β-estradiol, follicle-stimulating hormone, luteinizing hormone, and serum lipids, including triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-I, and apolipoprotein B100, were assessed at baseline and at 12 and 24 weeks after treatment.
Both the frequency of hot flushes and the Kupperman index score decreased in all three treatment groups during the intervention period, but the percentage decreases in both were significantly greater in the two isoflavone groups (44.3 ± 19.1 and 57.8 ± 37.4 [84 mg isoflavones]; 48.5 ± 27.2 and 56.7 ± 26.7 [126 mg isoflavones]) than in the placebo group (27.8 ± 15.5 and 34.6 ± 46.2; p < 0.01). There was no significant difference in the changes in estradiol, follicle-stimulating hormone, and luteinizing hormone among the three treatment groups during the study, and no significant differences were observed in the lipid components.
A daily supplement of 84 or 126 mg soy germ isoflavones may improve menopausal symptoms, although neither dose was found to affect lipid profiles in early postmenopausal Chinese women after 24 weeks of treatment. The favorable effects are unlikely to be associated with female hormones.
Phytoestrogens (PEs) are polyphenols of plant origin among which flavones, flavanones, isoflavones, coumarins, chalcones, lignans and stilbenes are the best representatives. By interacting with specific residues of the estradiol-binding pocket of estrogen receptors (ERs), they induce estrogenic responses, supporting the concept that they could be of benefits against the menopausal disorders due to endogenous estradiol depletion. According to literature data, PEs target a panel of proteins, suggesting that their effects are not limited to ER-dependent transcription pathways. In this regard, commercial preparations usually contain a mixture of compounds of which nature and concentration are not specified. Such mixtures being freely accessible and escaping thereby medical survey, they could exert unwanted effects, depending on their qualitative and quantitative composition as well as the physiopathological status of the women. This work outlines the necessity to inform consumers of the exact nature of these PEs preparations. Moreover, women who want to take PEs should inform their practitioner to be under strict medical survey. In the case of hormone-dependent cancer antecedents or predispositions, use of PEs is extremely inadvisable.
To evaluate for the first time in children the effect of soy-derived isoflavones on lipid profile and insulin resistance.
Twelve hypercholesterolemic children (8 females) aged 5.3 to 11.2 years have completed a prospective, controlled pilot study. After a low-fat diet for 12 weeks, children who maintained high cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels were randomly assigned to three intervention periods of either placebo or low and high dose isoflavone (16 or 48 mg) consumption, each period lasting 8 weeks.
The diet significantly reduced LDL-C and apolipoprotein B (Apo B) levels. However, isoflavones had no effect on cholesterol, LDL-C, high-density lipoprotein-cholesterol (HDL-C), triglycerides, lipoprotein (a), Apo B, or insulin resistance, at either low or high doses. Isoflavones had no effect on sex hormones, gonadotropins, sex-hormone binding globulin and thyroid hormones.
The results of this pilot study do not suggest a beneficial role of an isoflavone-enriched diet in children with hypercholesterolemia.
Recent interventional studies indicate that post-menopausal hormone replacement therapy is associated with an increased risk of cardiovascular mortality and breast cancer. Isoflavones, a class of plant estrogens, have structural similarities to estradiol. Hence, isoflavones may exert beneficial estrogenic health effects in postmenopausal women with fewer adverse effects.
To evaluate the effect of high-dose isoflavones on self-reported quality of life (QOL), cognition, lipoproteins and androgen status in post-menopausal women.
Double-blind, randomized, placebo-controlled, 12-week trial of 93 healthy, ambulatory, post-menopausal women (mean age 56 yr). The study was conducted at a tertiary care center in the United States.
Participants were randomly assigned to receive 20 g of soy protein containing 160 mg of total isoflavones vs taste-matched placebo (20 g whole milk protein). Both soy and the placebo were provided in the form of a powder to be mixed with beverages.
QOL was judged by the Menopause-specific Quality of Life (MENQOL) questionnaire while cognitive function was assessed with standard instruments. Total, free, and bioavailable testosterone, gonadotropins, SHBG, and fasting lipids were measured.
Eighty-four women (90%) completed the study (active=38, placebo=46). There was a significant improvement in all 4 QOL subscales (vasomotor, psychosexual, physical, and sexual) among the women taking isoflavones, while no changes were seen in the placebo group. No significant changes in cognition, serum androgens or plasma lipids were seen within any of the groups. However, at the end of the study, a group-by-time interaction was observed such that total testosterone and HDL levels were significantly lower in the isoflavones compared to placebo groups.
High-dose isoflavones is associated with improved QOL among women who have become menopausal recently. Hence, the timing of isoflavone supplementation with regards to the onset of menopause appears to be important. The use of isoflavones, as an alternative to estrogen therapy, may be potentially useful and seemingly safe in this group of women who are looking for relief from menopausal symptoms.
Soy protein intake has been postulated to improve lipid profiles, glucose homeostasis, and blood pressure. However, data linking soy protein intake and metabolic syndrome (MetS) are limited. We evaluated the association between soy protein intake and the risk of MetS and its components among middle-aged and elderly Chinese. A cross-sectional study was conducted among 2811 Chinese men and women aged 50-70 y, who were free of diagnosed cardiovascular diseases and cancers. Dietary data, including soy protein intake, was collected using a 74-item FFQ. MetS was defined using the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. We used multivariate logistical regression models to quantify these associations. The median level of soy protein intake was 7.82 g/d (7.64 g/d in men and 8.02 g/d in women). Overall, the association of soy protein intake and the risk of MetS differed between men and women (P for interaction = 0.008). In men, the adjusted odds ratio comparing the extreme quartiles was 1.64 (95% CI: 0.95-2.81; P-trend = 0.077), whereas for women, it was 0.66 (95% CI: 0.42-1.03; P-trend = 0.138). Soy protein intake was positively associated with hyperglycemia (P-trend = 0.005) in men, whereas it was inversely associated with elevated blood pressure (P-trend = 0.049). It was not associated with any component in women. In conclusion, habitual soy protein intake may have sex-dependent effects on risk of MetS in middle-aged and elderly Chinese.
The wide family of the phytoestrogens has become an alternative to the classical hormonal therapy in menopause; nevertheless, some findings are still conflicting.
To examine the effect of genistein administration on metabolic parameters and vascular reactivity considering the basal endocrine status of the patients.
A randomized placebo controlled study was conducted at a university hospital.
Fifty postmenopausal women participated.
Thirty subjects (group A) were randomized to receive 54 mg/d genistein while 20 subjects (group B) were treated with the placebo for 24 wk. In group A, we distinguish two subgroups: 14 normoinsulinemic and 12 hyperinsulinemic patients.
Anthropometric measures, hormonal and lipid assays, oral glucose tolerance test with glycemic, insulin, and C-peptide evaluation, indexes of insulin sensitivity and endothelial function, and euglycemic-hyperinsulinemic clamps were performed.
The insulin basal values significantly decreased in group A, whereas the homeostasis model index of insulin sensitivity and the fasting glucose levels significantly improved compared with placebo group. The genistein administration decreased fasting glucose and area under the curve glucose levels in the normoinsulinemic patients after treatment. In the hyperinsulinemic patients, a significant reduction in fasting insulin, fasting C-peptide, and area under the curve insulin levels as well as an increase in fractional hepatic insulin extraction was shown. In these patients, high-density lipoprotein cholesterol levels were significantly improved. The endothelium-dependent and -independent dilatation improved in the treated group. Normoinsulinemic patients showed both a significantly enhanced flow-mediated and nitrate-mediated dilatation, whereas no significant changes were found in the hyperinsulinemic group.
The glycoinsulinemic metabolism and the endothelial function were significantly influenced by genistein. In particular, normoinsulinemic patients showed an improvement in glycemic and vascular reactivity indexes. Conversely, an improvement in the insulin sensitivity indexes was noted in hyperinsulinemic patients.
We evaluated the interactive effect of polymorphisms in the sex hormone-binding globulin (SHBG) gene with soy isoflavones, tea consumption, and dietary fiber on endometrial cancer risk in a population-based, case-control study of 1,199 endometrial cancer patients and 1,212 controls. Genotyping of polymorphisms was performed by using TaqMan (Applied Biosystems, Foster City, CA) assays (rs6259) or the Affymetrix MegAllele Targeted Genotyping System (Affymetrix, Inc., US) (rs13894, rs858521, and rs2955617). Dietary information was obtained using a validated food frequency questionnaire. A logistic regression model was employed to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We found that the Asp(327)Asn (rs6259) polymorphism was associated with decreased risk of endometrial cancer, particularly among postmenopausal women (OR = 0.79, 95% CI = 0.62-1.00). This single nucleotide polymorphism (SNP) modified associations of soy isoflavones and tea consumption but not fiber intake with endometrial cancer, with the inverse association of soy intake and tea consumption being more evident for those with the Asp/Asp genotype of the SHBG gene at Asp(327)Asn (rs6259), particularly premenopausal women (P(interaction) = 0.06 and 0.02, respectively, for soy isoflavones and tea intake). This study suggests that gene-diet interaction may play an important role in the etiology of endometrial cancer risk.
To measure the association between use of estrogenic botanical supplements and serum sex hormones in postmenopausal breast cancer survivors, a total 502 postmenopausal women were queried 2-3 years after breast cancer diagnosis about their use of botanical supplements, and supplements were categorized according to their estrogenic properties. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin. Adjusted means of the serum hormones were calculated by use of estrogenic supplements. Women reporting use of any estrogenic botanical supplement had significantly lower levels of estrone (20.8 vs. 23.6 pg/ml), estradiol (12.8 vs. 14.7 pg/ml), free estradiol (0.29 vs. 0.35 pg/ml), and DHEAS (47.7 vs. 56.2 microg/dl) compared to women reporting no use. Data from this cross-sectional study suggest the use of estrogenic botanical supplements may be associated with sex hormone concentrations in breast cancer survivors. Considering the high use of these supplements among breast cancer patients, further research is needed to clarify the relative estrogenicity/antiestrogenicity of these compounds and their relation with prognosis.
Intervention data suggest a cardioprotective role for supplemental isoflavones; however, few studies have examined the cardiovascular disease (CVD) benefit of usual dietary isoflavone intake. This cross-sectional study examined the association between usual dietary isoflavone intake and CVD risk factors, including lipids and lipoproteins, body mass index (BMI) and fat distribution, blood pressure, glucose and insulin. Subjects were postmenopausal women (n = 208) aged 45-74 y, who attended screening and baseline visits for a randomized, double-blind, placebo-controlled trial examining the effects of isoflavone use. At screening, total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol were measured, and demographic, behavioral and menopausal characteristics were assessed. One month later, dietary intake over the past year was assessed with a standardized questionnaire. Anthropometric measurements and blood pressure were obtained, and a 75-g oral glucose tolerance test was administered. Isoflavone consumption did not vary by age, exercise, smoking, education or years postmenopausal. Women with high genistein intake had a significantly lower BMI (P-trend = 0.05), waist circumference (P-trend = 0.05) and fasting insulin (P-trend = 0.07) than those with no daily genistein consumption. In adjusted analyses, genistein, daidzein and total isoflavone intake were each positively associated with HDL cholesterol (P = 0.05) and inversely associated with postchallenge insulin (P = 0.05). These data suggest a protective role for dietary soy intake against CVD in postmenopausal women.
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