phytoestrogens and Coronary-Disease

Menopause is a critical period during which, without timely interventions, increased risks of cardiovascular and metabolic diseases, osteoporosis, sexual dysfunction and premature cognitive decline will contribute to diminished quality-of-life in women. Hormone therapy (HT) used to be the standard of care for managing vasomotor symptoms and prevention of chronic diseases until publication of the Women's Health Initiative (WHI) in 2002. Concerned about risks highlighted in WHI publications, many symptomatic women promptly ceased HT which resulted in increased vasomotor symptoms, osteoporosis-related-fractures and insomnia. Data from post-hoc WHI analyses and newer clinical trials consistently show reductions in coronary heart disease and mortality when estrogen therapy is initiated soon after menopause, whereas administration in later years and/or in combination with progesterone carries increased risks. However, no validated primary preventive strategies are available for younger postmenopausal women (<60 years), highlighting the need to re-evaluate the use of estrogen alone for which the risk-benefit balance appears positive. In contrast, in older women (>60 years), risks associated with oral HT exceed benefits; however transdermal estrogen may offer a safer alternative and should be further evaluated. Alternative therapies such as phytoestrogens and non-hormonal prescriptions may be beneficial for older women or those who are unsuitable for HT. Long-term head-to-head comparisons of HT with alternative interventions are warranted to confirm their efficacy for chronic disease prevention.

Topics: Aged; Aged, 80 and over; Clinical Trials as Topic; Coronary Disease; Dementia; Estradiol; Estrogen Replacement Therapy; Female; Humans; Menopause; Middle Aged; Phytoestrogens; Postmenopause; Resveratrol; Risk Assessment; Time Factors; Women's Health

Phytoestrogens are naturally occurring plant-derived phytochemicals, whose common biological roles are to protect plants from stress or to act as part of a plant's defense mechanism. Although composed of a wide group of nonsteroidal compounds of diverse structure, phytoestrogens have been shown to bind estrogen receptors and to behave as weak agonist/antagonist in both animals and humans. Phytoestrogens include mainly isoflavones (IF), coumestans, and lignans. These compounds are known to be present in fruits, vegetables, and whole grains commonly consumed by humans. IF are found in legumes--mainly soybeans--whereas flaxseed is a major source of lignans, and coumestans are significantly present in clover, alfalfa and soybean sprouts. 8-Prenyl flavonoids are common in vegetables. Bioavailability of IF requires an initial hydrolysis of the sugar moiety by intestinal beta-glucosidases to allow the following uptake by enterocytes and the flow through the peripheral circulation. Following absorption, IF are then reconjugated mainly to glucuronic acid and to a lesser degree to sulphuric acid. Gut metabolism seems key to the determination of the potency of action. Several epidemiological studies correlated high dose consumptions of soy IF with multiple beneficial effects on breast and prostate cancers, menopausal symptoms, osteoporosis, atherosclerosis and stroke, and neurodegeneration. For the relief of menopausal symptoms a consumption of 60 mg aglycones/day has been suggested; for cancer prevention a consumption between 50 and 110 mg aglycones/day is considered beneficial to reduce risks of breast, colon and prostate cancer; to decrease cardiovascular risk a minimum intake of 40-60 mg aglycones/day, together with about 25 g of soy protein has been suggested. For improvement in bone mineral density, 60-100 mg aglycones/day for a period of at least 6-12 months could be beneficial.

Topics: Biological Availability; Breast Neoplasms; Coronary Disease; Diet; Fruit; Glycine max; Health Promotion; Humans; Intestinal Absorption; Isoflavones; Osteoporosis; Phytoestrogens; Safety; Vegetables

A recently (2002) published, randomised, double blind placebo controlled trial of hormone replace ment therapy (HRT), the Women's Health Initiative (WHI), is not consistent with the decrease in cardiovascular disease under CEE/HPA seen in observational primary prevention studies like the Nurses' Health Study. Baseline characteristics of participants like age, body mass index, years since menopause and preexistent cardiovascular diseases may be responsible for the lack of benefit seen in this trial. Clinical outcome data of HRT from randomised trials in secondary prevention of cardiovasular diseases are limited. The first prospective, randomised placebo controlled trial, the Heart and Estrogen/Progestin Replacement Study (HERS) in secondary prevention did not show any difference in CHD events between treatment groups and placebo during a follow up of 4.1 years. However, an increased risk of CHD was seen especially during the first year on HRT, subsequent years showed a decrease in event rate compared with never-users. One explanation for this lack of benefit may be a bi-directional effect of estrogen - early risk and late benefit - especially in an elderly study population with established atherosclerotic lesions. In postmenopausal women, estrogen replacement therapy affects LDL- and HDL-cholesterol levels favorably, causes vasodilatation by activating NOS, inhibits platelet aggregation and proinflammatory cell adhesion on endothelial cells of vascular wall. Estrogen can affect the cardiovascular system adversely by increasing triglycerid levels, CPR and proinflammatory cytokines like tumor necrosis factor alpha (TNF-alpha). Alternatives to HRT like phytoestrogens act via estrogen alpha and beta receptor modulation. Phytoestrogens may lower LDL-cholesterol levels without increasing triglyceride levels, they have shown antioxidannt properties as well as favorable effects on vascular reactivity. The importance of HRT and phytoestrogens in primary and secondary prevention of cardiovascular disease remains to be established.

Topics: Aged; Cardiovascular System; Coronary Disease; Double-Blind Method; Estrogen Replacement Therapy; Female; Follow-Up Studies; Humans; Middle Aged; Myocardial Infarction; Phytoestrogens; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome

Cardiovascular disease is the leading cause of death among men and women in Western societies. Over the past decade, interest in a better understanding of gender differences in cardiovascular disease has heightened. Concomitantly, the use of hormone therapy for cardiovascular risk reduction in postmenopausal women has come into question in light of recent landmark clinical studies casting doubt on the benefits of this therapy. As a consequence, alternatives to conventional hormone replacement, including selective estrogen receptor modulators and phytoestrogens, have attracted considerable attention. The authors provide an up-to-date review of the clinical actions of selective estrogen receptor modulators on cardiovascular disease. The actions of tamoxifen, raloxifene, droloxifene, and soy phytoestrogens are discussed in the context of cardiovascular disease epidemiology, coronary events, clinical markers of cardiovascular risk, and vascular function. In addition, the authors' current understanding of the mechanism of action of these agents is discussed and recommendations for clinical practice are reviewed.

Topics: Arteriosclerosis; Cardiovascular Diseases; Coronary Disease; Female; Hormone Replacement Therapy; Humans; Isoflavones; Lipids; Phytoestrogens; Plant Preparations; Plants; Postmenopause; Selective Estrogen Receptor Modulators

Chemicals known to disrupt the endocrine system of animal models are assessed for their potential impact on the health of menopausal and postmenopausal women. These "endocrine disrupters" consist of two groups of compounds - man-made and naturally occurring. There is some evidence to suggest that the naturally occurring phytoestrogens, derived from plant material, may have some beneficial effects on menopausal symptoms and the risk of breast cancer, cardiovascular disease and osteoporosis. Further studies are required to confirm these possibilities. Some man-made environmental pollutants appear to increase the risk of breast cancer, although again the evidence is inconclusive. Mechanistic experiments indicate that these chemicals interact with oestrogen receptors and alter metabolism in a number of different ways, some of which may be important in postmenopausal women. Further investigation of the differences in mode of action between the man-made and the natural endocrine disrupters may lead to important insights into their effects on women's health.

Topics: Aged; Animals; Breast Neoplasms; Coronary Disease; Endocrine System; Environmental Pollutants; Female; Humans; Menopause; Middle Aged; Neoplasms, Hormone-Dependent; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Risk Assessment; Uterine Neoplasms; Women's Health

Interest in the physiological role of bioactive compounds present in plants has increased dramatically over the last decade. Of particular interest in relation to human health are the class of compounds known as the phytoestrogens, which embody several groups of non-steroidal oestrogens including isoflavones & lignans that are widely distributed within the plant kingdom. Data from animal and in vitro studies provide plausible mechanisms to explain how phytoestrogens may influence hormone dependent states, but although the clinical application of diets rich in these oestrogen mimics is in its infancy, data from preliminary studies suggest potential beneficial effects of importance to health. Phytoestrogens are strikingly similar in chemical structure to the mammalian oestrogen, oestradiol, and bind to oestrogen receptors (ER) with a preference for the more recently described ER beta. This suggests that these compounds may exert tissue specific effects. Numerous other biological effects independent of the ER (e.g. antioxidant capacity, antiproliferative and antiangiogenic effects) have been ascribed to these compounds. Whether phytoestrogens have any biological activity in humans, either hormonal or non hormonal is a contentious issue and there is currently a paucity of data on human exposure. Much of the available data on the absorption and metabolism of dietary phytoestrogens is of a qualitative nature; it is known that dietary phytoestrogens are metabolised by intestinal bacteria, absorbed, conjugated in the liver, circulated in plasma and excreted in urine. Recent studies have addressed quantitatively what happens to isoflavones following ingestion--with pure compound and stable isotope data to compliment recent pharmacokinetic data for soy foods. The limited studies conducted so far in humans clearly confirm that soya isoflavones can exert hormonal effects. These effects may be of benefit in the prevention of many of the common diseases observed in Western populations (such as breast cancer, prostate cancer, menopausal symptoms, osteoporosis) where the diet is typically devoid of these biologically active naturally occurring compounds. However since biological effects are dependent on many factors including dose, duration of use, protein binding affinity, individual metabolism and intrinsic oestrogenic state, further clinical studies are necessary to determine the potential health effects of these compounds in specific population groups. However we cur

Topics: Animals; Breast Neoplasms; Coronary Disease; Diet; Endometrial Neoplasms; Estrogens, Non-Steroidal; Female; Humans; Infant; Infant Food; Intestinal Absorption; Isoflavones; Lignans; Male; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Premenopause; Risk Factors

Dietary isoflavones are currently receiving much attention because of their potential role in preventing coronary artery disease and other chronic diseases. Accumulating evidence from cell culture and laboratory animal experiments indicates that isoflavones have the potential to prevent or delay atherogenesis. Suggested mechanisms of action include: a reduction in low-density lipoprotein (LDL) cholesterol and a potential reduction in the susceptibility of the LDL particle to oxidation; (2) an improvement in vascular reactivity; (3) an inhibition of pro-inflammatory cytokines, cell adhesion proteins and nitric oxide (NO) production; and (4) an inhibition of platelet aggregation. These mechanisms are consistent with the epidemiological evidence that a high consumption of isoflavone-rich soy products is associated with a reduced incidence of coronary artery disease. Biological effects of isoflavones are dependent on many factors, including dose consumed, duration of use, protein-binding affinity, and an individual's metabolism or intrinsic oestrogenic state. Further clinical studies are necessary to determine the potential health effects of isoflavones in specific population groups as we currently know little about age-related differences in exposure to these compounds and there are few guidelines on optimal dose for cardiovascular health benefits.

Topics: Animals; Atherosclerosis; Coronary Disease; Diet; Female; Humans; Isoflavones; Lipids; Male; Phytoestrogens; Receptors, Estrogen; Tissue Distribution

Topics: Animals; Coronary Disease; Dibutyl Phthalate; Dioxins; Environmental Pollutants; Estrogens, Non-Steroidal; Humans; Isoflavones; Phytoestrogens; Plant Preparations; Zearalenone

Topics: Animals; Bone Density; Breast Neoplasms; Cognition; Coronary Disease; Endometrial Neoplasms; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Osteoporosis; Patient Compliance; Phytoestrogens; Plant Preparations; Risk Assessment; Soybean Proteins; Treatment Outcome

Coronary artery disease is the leading overall cause of mortality for women and increases dramatically after menopause. Estrogen has many beneficial cardiovascular actions although concerns have been raised about its effects on the progression of breast and uterine neoplasms and its tendency to increase coagulability. Selective estrogen agonists may be superior to conventional estrogens. A dietary source of a partial estrogen agonist is the plant-based group of phytoestrogens, which include isoflavones, lignans and coumestans. Phytoestrogens have a similar structure to estradiol and have weak affinity for the estrogen receptor. Epidemiologic data indicate that women ingesting high amounts of phytoestrogens, particularly as isoflavones in soy products, have less cardiovascular disease, breast and uterine cancer and menopausal symptoms than those eating Western diets. Preclinical and clinical studies have found that isoflavones have lipid-lowering effects as well as the ability to inhibit low-density lipoprotein oxidation. They have been shown to normalize vascular reactivity in estrogen-deprived primates. Furthermore, phytoestrogens have antineoplastic effects with inhibition of cellular proliferation as well as angiogenesis, properties that could be protective against cancer development. Finally, menopausal symptoms and bone density may be favorably influenced by phytoestrogens. In summary, phytoestrogens, in the form of dietary isoflavones, represent a new area to explore in pursuit of nutritional approaches to cardiovascular protection.

Topics: Aged; Coronary Disease; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Middle Aged; Phytoestrogens; Plant Preparations; Survival Rate; Treatment Outcome

Soy protein-containing foods are a rich source of isoflavone phytoestrogens, such as genistein and daidzein. There is great interest in these substances, as lower rates of chronic diseases, including coronary heart disease, have been associated with high dietary intake of soy-containing foods. Soy phytoestrogens bind weakly to estrogen receptors, and some bind more strongly to estrogen receptor-beta compared with estrogen receptor-alpha. A meta-analysis has indicated that isoflavone phytoestrogens lowered plasma cholesterol concentrations in subjects with initially elevated levels, but had little effect in subjects with normal cholesterol concentrations. These substances reportedly may also have beneficial effects on arterial endothelial function. In addition to these potentially antiatherogenic effects, many laboratories are investigating other possible mechanisms, including antioxidative and antiproliferative properties of these substances. We have shown that dietary supplementation with soy-derived isoflavones reduced the in vitro oxidation susceptibility of low-density lipoprotein (LDL). To further explore this phenomenon, we incorporated genistein and daidzein into LDL molecules in vitro with the aid of an artificial transfer system. However, it was necessary to convert the isoflavone molecules to fat-soluble derivatives, fatty acid esters (analogous to esterified endogenous estrogens, which are known to occur in vivo), to achieve significant incorporation. The LDLs containing esterified isoflavones were shown to be less susceptible to oxidation in vitro than native LDL. We also employed U937 cell cultures for investigating the effects of isoflavone-containing LDLs on cell proliferation. Some of these LDLs exhibited antiproliferative effects in cultured U937 cells. In summary, lipophilic phytoestrogen derivatives could be incorporated into LDLs, increasing their oxidation resistance and antiproliferative efficacy ex vivo, both of which are, in theory, antiatherogenic effects. Further studies are needed to assess to what extent analogous effects could be produced in vivo and whether such substances have a role in hormone replacement and coronary heart disease prevention in postmenopausal women.

Topics: Antioxidants; Coronary Disease; Diet; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Lipids; Lipoproteins; Phytoestrogens; Plant Preparations

CHD is a major cause of morbidity and mortality in women. The incidence of CHD in premenopausal women is low but increases substantially after the menopause, and this difference suggests that endogenous oestrogens are cardioprotective. Observational prospective studies have consistently shown that exogenous oestrogens also lower CHD risk. The biological mechanisms by which endogenous and exogenous oestrogens exert their protective effect are multifactorial, affecting lipids, carbohydrate metabolism, body fat distribution and blood pressure. The prevention of CHD with oestrogen therapy is therefore aimed both at correction of the traditional risk factors and at direct control of vessel structure and function. The wide international variation in rates of CHD together with the lower mortality in sub-groups of the population suggests that a considerable proportion of CHD may be prevented by dietary modification. Since phyto-oestrogens are structually similar to oestrogen, they have the potential to mimic its effects in vivo. The hypocholesterolaemic effects of soyabean protein (rich in phyto-oestrogen precursors) are well established, but the underlying mechanism and atherogenic potential of these changes are unknown. One isoflavone, genistein, has been shown in vitro to exert effects which may slow the development of atherosclerotic disease. However, further studies are required to determine the dose-related changes induced by phyto-oestrogens on serum lipoproteins, haemostasis and vascular function.

Topics: Coronary Disease; Diet; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Menopause; Phytoestrogens; Plant Preparations; Plants

Limited acceptable alternatives to hormone replacement therapy exist for use by postmenopausal women. This oversight within the biomedical community is of particular concern considering the increasing number of postmenopausal women and the current low use of hormone replacement therapy. In addition, contraindications to hormone replacement therapy and controversies regarding recommendations for use of hormone replacement therapy also exist. With the notable exception of the advances in prevention of osteoporosis, alternatives to estrogen for other aspects of the sequelae of hypoestrogenism or aging are limited. Furthermore, there is widespread use of complementary therapies among postmenopausal women despite a lack of data on efficacy or safety of such therapies. Increased research into alternatives to estrogen for menopausal women is of clinical, scientific, and health policy importance.

Topics: Antioxidants; Climacteric; Contraindications; Coronary Disease; Estrogen Replacement Therapy; Estrogens; Estrogens, Non-Steroidal; Female; Health Promotion; Humans; Isoflavones; Menopause; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Plants; Progestins; Risk Factors; United States

Phyto-oestrogens have emerged from their esoteric role in animal husbandry following the hypothesis that the human Western diet is relatively deficient in these substances compared with societies where large amounts of plant foods and legumes are eaten. Evidence is beginning to accrue that they may begin to offer protection against a wide range of human conditions, including breast, bowel, prostate and other cancers, cardiovascular disease, brain function, alcohol abuse, osteoporosis and menopausal symptoms. Of the two main classes of these weak oestrogens, the isoflavones are under intensive investigation due to their high levels in soyabean. Like the 'anti-oestrogen' Tamoxifen, these seem to have oestrogenic effects in human subjects in the cardiovascular system and bone. Although previously only available from food, isoflavones are now being marketed in health-food supplements or drinks, and tablets may soon be available over the counter as 'natural' hormone-replacement therapy. In cancer, anti-oestrogenic effects are thought to be important, although genistein especially has been shown to induce wide-ranging anti-cancer effects in cell lines independent of any hormone-related influence. There are few indications of harmful effects at present, although possible proliferative effects have been reported. In infants, the effects of high levels in soya milk formulas are uncertain. The second group, lignans, have been less investigated despite their known antioestrogenic effects and more widespread occurrence in foods. Investigation of the possible benefits of phyto-oestrogens is hampered by lack of analytical standards and, hence, inadequate methods for the measurement of low levels in most foods. This problem may prove to be a major dilemma for regulatory authorities, clinicians and others wishing to advise the general public on whether these compounds really do have the health benefits attributed to them.

Topics: Coronary Disease; Diet; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Male; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Risk Factors

While there have been ample studies of a cross-cultural nature and experimental evaluations establishing the cardioprotective effect of soy protein, efforts to clarify the proportion of those benefits related to its phytoestrogen content are relatively recent. In most cases, the general approach to evaluating the role of soy's phytoestrogens has been to compare the cardiovascular benefits of isolated soy protein with a comparable soy protein isolate that has been alcohol extracted. Based on that approach, soy phytoestrogens appear to lower low-density lipoprotein concentrations while increasing plasma concentrations of the high-density lipoproteins. Particularly noteworthy with respect to the high-density lipoprotein effects are the increases in apolipoprotein A-1. Phytoestrogens may also prevent the oxidation of lipoprotein particles. The soy phytoestrogens favourably influence coronary artery reactivity. They also inhibit the progression of atherosclerosis in the coronary, iliac and common and internal carotid arteries. The cardiovascular benefits of soy phytoestrogens appear to be equal for males and females.

Topics: Apolipoprotein A-I; Coronary Disease; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Lipoproteins, HDL; Lipoproteins, LDL; Male; Phytoestrogens; Plant Preparations; Soybean Proteins

Epidemiological studies have revealed that high levels of lignans and isoflavonoids are frequently associated with low breast, prostate and colon cancer risk, as well as a low risk of coronary heart disease. These compounds seem to be cancer protective and/or are biomarkers of a 'healthy' diet. All soy protein products consumed by Asian populations have high concentrations of isoflavonoids. In other countries, such as Finland and Sweden, the lignan levels are higher in populations with the lowest risk because of a high consumption of whole-grain rye bread, berries and some vegetables. There is a strong association between fibre intake per kilogram body weight and lignan concentrations in body fluids. Breast cancer has been found to be associated with low lignan levels in the USA, Finland, Sweden and Australia. With regard to prostate and colon cancer, as well as coronary heart disease, the epidemiological data related to phytoestrogens are still very limited.

Topics: Breast Neoplasms; Coronary Disease; Diet; Epidemiology; Estrogens, Non-Steroidal; Humans; Isoflavones; Lignans; Male; Phytoestrogens; Plant Preparations; Prostatic Neoplasms

The evidence that natural isoflavones protect against several chronic diseases is both observational and experimental. In humans, epidemiologic findings clearly show a higher incidence of some common types of cancer (i.e., breast, prostate, and colon) and of coronary heart diseases in Western populations exposed to limited amounts of soybean isoflavones (i.e., genistein, daidzein) in the diet. Further evidence for cancer and cardiac protection and antiatherogenic effects resulting from soybean isoflavones administration has been noted in various experimental animal models. Isoflavones may also prevent postmenopausal bone loss and osteoporosis. In fact, genistein has been reported to be as active as estrogens in maintaining bone mass in ovariectomized rats. Moreover, the synthetic isoflavone derivative ipriflavone is able to reduce bone loss in various types of animal models of experimental osteoporosis providing a rationale on its use in the prevention and treatment of postmenopausal and senile osteoporosis in humans. The mechanism through which isoflavones may exert the above-mentioned effects seems to depend, at least in part, on their mixed estrogen agonist-antagonist properties. An alternative hypothetical mechanism could derive from other biochemical actions of isoflavones such as inhibition of enzymatic activity, in particular protein kinases, or activation of an "orphan" receptor distinct from the estrogen type I receptor.

Topics: Animals; Coronary Disease; Diet; Disease Models, Animal; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Plants; Receptors, Estrogen

The wide distribution of plant estrogens or 'phytoestrogens' in cereals, vegetables and medicinal plants raises questions concerning the possible health risks and benefits associated with their consumption. In this article, we provide a synopsis of the literature relating principally to the clinical effects of phytoestrogens on the diseases associated with ageing. The sources, metabolism and properties of the different phytoestrogens are also discussed. The studies included were primarily restricted to those with data pertinent to clinical practice. Our contention is that phytoestrogens are at least part of the reason why vegetarians and Asian populations have a low rate of cancer and heart disease.

Topics: Adult; Aged; Climacteric; Colorectal Neoplasms; Coronary Disease; Cross-Cultural Comparison; Diet, Vegetarian; Estrogens, Non-Steroidal; Feeding Behavior; Female; Glycine max; Humans; Isoflavones; Male; Middle Aged; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations

The aim of this study was to investigate acute vasodilator responses to phytoestrogens and selective estrogen receptor-alpha (ERalpha) agonist in isolated small arteries from men with established coronary heart disease (CHD) and with a history of myocardial infarction versus healthy male control subjects. As to methodology, small arteries obtained from subcutaneous fat biopsies and mounted on a wire myograph were preconstricted with norepinephrine, and dilator responses to increasing nanomolar-micromolar concentrations of the phytoestrogens resveratrol and genistein (predominantly ERbeta agonists) and to propyl-[1H]-pyrazole-1,3,5-triyl-trisplenol (PPT, a selective ERalpha agonist) were determined. These were compared with responses to reference compound 17beta-estradiol (17beta-E2). Concentration-response curves were constructed before and after nitric oxide (NO) synthase inhibition with Nomega-nitro-L-arginine methyl ester. As a result, relaxation induced by the investigated compounds was similar in men with CHD and control men, but in both groups PPT and genistein-induced relaxation was greater than that of resveratrol and 17beta-E2. NO contributed to both phytoestrogens and PPT-induced relaxation but not to 17beta-E2 responses in arteries from control men. This NO-mediated component of relaxation was absent in arteries from men with established CHD. In conclusion, phytoestrogens, at concentrations achievable by ingestion of phytoestrogen-rich food products, evoke dilatation ex vivo of small peripheral arteries from normal men and those with established CHD. The contribution of NO to dilatory responses by these compounds is pertinent to arteries from control males, whereas other NO-independent dilatory mechanism(s) are involved in arteries from CHD.

Topics: Administration, Oral; Adult; Aged; Arteries; Coronary Disease; Genistein; Humans; Male; Middle Aged; Nitric Oxide; Phytoestrogens; Resveratrol; Stilbenes; Time Factors; Treatment Outcome; Vasodilation

Phytoestrogens have been suggested to lower cardiovascular disease risk, but existing research focused on non-Western high intake levels and on risk factors. We investigated whether habitual low phytoestrogen intake is associated with manifest cardiovascular disease risk.. Between 1993 and 1997, 16,165 women 49 to 70 years old and free from cardiovascular disease were enrolled in the Dutch Prospect-EPIC cohort (European Prospective study Into Cancer and nutrition) and followed up for a median period of 75 months. At enrollment, women filled in questionnaires on chronic disease risk factors and nutrition. Intake of phytoestrogens was estimated using the food frequency questionnaire covering regular dietary intake of 178 food items in the year before enrollment. Cox regression analysis was used to estimate hazard ratios of cardiovascular disease for quartiles of phytoestrogen intake adjusted for age at intake, body mass index, smoking, physical activity, hypertension, hypercholesterolemia, use of hormone replacement therapy, menopausal status, and intake of total energy, total fiber, vegetables, fruit, and alcohol. In total, 372 women experienced a coronary event (CHD) (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9], 410 to 414, 427.5) and 147 women a cerebrovascular event (CVD) (ICD-9, 430 to 438) during follow-up. Overall, neither isoflavones nor lignans were associated with decreased cardiovascular disease risk. When stratifying for ever versus never smokers, CHD risk decreased with increasing lignan intake for ever smokers.. Our results do not support the presence of a protective effect of higher intake of phytoestrogens in low doses on cardiovascular disease risk, although a small risk reduction with higher lignan intake cannot be excluded for smokers.

Topics: Aged; Alcohol Drinking; Body Mass Index; Cardiovascular Diseases; Cohort Studies; Coronary Disease; Dietary Fiber; Energy Intake; Feeding Behavior; Female; Follow-Up Studies; Fruit; Hormone Replacement Therapy; Humans; Hypercholesterolemia; Hypertension; Isoflavones; Lignans; Menopause; Middle Aged; Netherlands; Nutrition Surveys; Phytoestrogens; Proportional Hazards Models; Prospective Studies; Risk; Smoking; Stroke; Surveys and Questionnaires; Vegetables

Epidemiological evidence suggests that populations consuming large amounts of soy protein have a reduced incidence of coronary heart disease (1-5). The cardiovascular risks associated with conventional hormone replacement therapy in postmenopausal women (5-7) have precipitated a search for alternative estrogen receptor modulators. Here we report that long-term feeding of rats with a soy protein-rich (SP) diet during gestation and adult life results in decreased oxidative stress, improved endothelial function, and reduced blood pressure in vivo measured by radiotelemetry in aged male offspring. Improved vascular reactivity in animals fed an SP diet was paralleled by increased mitochondrial glutathione and mRNA levels for endothelial nitric oxide synthase (eNOS) and the antioxidant enzymes manganese superoxide dismutase and cytochrome c oxidase. Reduced eNOS and antioxidant gene expression, impaired endothelial function, and elevated blood pressure in animals fed a soy-deficient diet was reversed after refeeding them an SP diet for 6 months. Our findings suggest that an SP diet increases eNOS and antioxidant gene expression in the vasculature and other tissues, resulting in reduced oxidative stress and increased NO bioavailability. The improvement in endothelial function, increased gene expression, and reduced blood pressure by soy isoflavones have implications for alternative therapy for postmenopausal women and patients at risk of coronary heart disease.

Topics: Animal Feed; Animals; Antioxidants; Aorta; Blood Pressure; Coronary Disease; Endothelium, Vascular; Female; Gene Expression Regulation, Enzymologic; Genistein; Glycine max; Isoflavones; Liver; Male; Malondialdehyde; Models, Biological; Models, Chemical; Nitric Oxide Synthase Type III; Oxidative Stress; Phytoestrogens; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors

Topics: Antioxidants; Blood Glucose; Coronary Disease; Dietary Fiber; Edible Grain; Humans; Lipids; Phytoestrogens

Recent randomized trials of hormone replacement therapy (HRT) in postmenopausal women are not consistent with the decrease in cardiovascular risk seen in observational studies of hormone therapy users compared with nonusers. Emerging evidence indicates that HRT use in some women with established coronary heart disease may be associated with prothrombotic effects or proinflammatory effects leading to adverse events. In healthy women, the decision to use HRT should be based primarily on noncardiac factors until more data becomes available that is relevant to this population. Several alternatives to HRT, including phytoestrogens and selective estrogen receptor modulators, have favorable effects on cardiovascular risk factors, but their impact on clinical outcomes remains to be determined.

Topics: Coronary Disease; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Middle Aged; Phytoestrogens; Plant Preparations; Postmenopause; Primary Prevention; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators; Tamoxifen

Topics: Coronary Disease; Estrogens, Non-Steroidal; Humans; Isoflavones; Phytoestrogens; Plant Preparations; Plants

Topics: Aged; Analysis of Variance; Coronary Disease; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Linear Models; Male; Middle Aged; Phytoestrogens; Plant Preparations; Prolactin; Sex Factors; Tea

Topics: Coronary Disease; Estrogens, Non-Steroidal; Female; Hot Flashes; Humans; Isoflavones; Menopause; Phytoestrogens; Plant Preparations; Soybean Proteins

Phytoestrogens are estrogen mimics produced mainly by leguminous plants, like clover, lucerne and soya beans, but also by some grasses and other plants. They are isoflavones and other plant phenols, bearing no resemblance to natural estrogens, but somewhat similar to non-steroidal synthetic estrogens, like diethylstilbestrol. Normally they have little ill effect on herbivores, but in large doses they can result in prolonged periods of estrus. It is suggested that when consumed by lactating cows, the estrogenic substance appears in their milk and transferred to the human consumer, on whom the effect could be similar to that of diethylstilbestrol - a substance with well substantiated atherogenic properties. This could be the explanation of the strong positive correlation between the consumption of mild and mortality from coronary disease reported in previous papers of the writer and other authors, and also of the differences between male and female mortality from coronary disease. When phytoestrogens are consumed directly in plants like soya beans, they appear to be correlated with cerebrovascular disease.

Topics: Animals; Cattle; Coronary Disease; Estrogens; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Milk; Phytoestrogens; Plant Preparations; Plants