phytoestrogens and Heart-Diseases

Phytoestrogens are plant derived compounds found in a wide variety of foods, most notably soy. A litany of health benefits including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms, are frequently attributed to phytoestrogens but many are also considered endocrine disruptors, indicating that they have the potential to cause adverse health effects as well. Consequently, the question of whether or not phytoestrogens are beneficial or harmful to human health remains unresolved. The answer is likely complex and may depend on age, health status, and even the presence or absence of specific gut microflora. Clarity on this issue is needed because global consumption is rapidly increasing. Phytoestrogens are present in numerous dietary supplements and widely marketed as a natural alternative to estrogen replacement therapy. Soy infant formula now constitutes up to a third of the US market, and soy protein is now added to many processed foods. As weak estrogen agonists/antagonists with molecular and cellular properties similar to synthetic endocrine disruptors such as Bisphenol A (BPA), the phytoestrogens provide a useful model to comprehensively investigate the biological impact of endocrine disruptors in general. This review weighs the evidence for and against the purported health benefits and adverse effects of phytoestrogens.

Topics: Animals; Brain; Breast Neoplasms; Diethylstilbestrol; Endocrine Disruptors; Female; Genitalia; Heart Diseases; Humans; Male; Menopause; Menstrual Cycle; Mice; Osteoporosis; Phytoestrogens; Puberty; Rats; Sexual Behavior; Soybean Proteins

Biological sex plays an important role in normal cardiac physiology as well as in the heart's response to cardiac disease. Women generally have better cardiac function and survival than do men in the face of cardiac disease; however, this sex difference is lost when comparing postmenopausal women with age-matched men. Animal models of cardiac disease mirror what is seen in humans. Sex steroid hormones contribute significantly to sex-based differences in cardiac disease outcomes. Estrogen is generally considered to be cardioprotective, whereas testosterone is thought to be detrimental to heart function. Environmental estrogen-like molecules, such as phytoestrogens, can also affect cardiac physiology in both a positive and a negative manner.

Topics: Animals; Disease Models, Animal; Estrogens; Female; Heart; Heart Diseases; Humans; Male; Mice; Phytoestrogens; Sex Characteristics; Testosterone

Topics: Animals; Cardiovascular Physiological Phenomena; Diet; Estrogens, Non-Steroidal; Female; Gonadal Steroid Hormones; Heart; Heart Diseases; Humans; Isoflavones; Male; Phytoestrogens; Plant Preparations; Sex Characteristics

Topics: Animals; Antioxidants; Diet; Disease Models, Animal; Estrogens; Estrogens, Non-Steroidal; Female; Genistein; Growth Inhibitors; Heart Diseases; Humans; Isoflavones; Male; Neoplasms; Neoplasms, Experimental; Neovascularization, Pathologic; Phytoestrogens; Plant Preparations

Lignans and phytoestrogens have been associated with protective effect against hormone-related diseases, for example, cancer of the breast and prostate, and potential mechanisms for this effect have been reported. Antioxidants also appear to have some protective effect against diseases associated with reactive free radicals such as coronary heart disease and cancer. Whole grains contain some of these substances particularly the mammalian lignan precursors, vitamin E, other phenolic compounds, Se, and phytic acid. These substances may in part be responsible for the reduced risk of cancer and coronary heart disease associated with intake of high-fiber diets containing whole grains. Because they are more associated with the fiber in the outer layers of the grain, the intake of whole vs. refined grain is emphasized for optimum health benefits.

Topics: Antioxidants; Edible Grain; Estrogens; Estrogens, Non-Steroidal; Health Promotion; Heart Diseases; Hormones; Humans; Isoflavones; Lignans; Neoplasms; Phytoestrogens; Plant Preparations

There has been substantial interest in phytoestrogens, because of their potential effect in reducing cancer and heart disease risk. Measuring concentrations of phytoestrogens in urine is an alternative method for conducting epidemiological studies. Our objective was to evaluate the urinary excretion of phytoestrogens as biomarkers for dietary phytoestrogen intake in Mexican women. Participants were 100 healthy women from 25 to 80 years of age. A food frequency questionnaire (FFQ) and a 24 h recall were used to estimate habitual and recent intakes of isoflavones, lignans, flavonols, coumestrol, resveratrol, naringenin, and luteolin. Urinary concentrations were measured by liquid chromatography (HPLC) coupled to mass spectrometry (MS) using the electrospray ionization interface (ESI) and diode array detector (DAD) (HPLC-DAD-ESI-MS). Spearman correlation coefficients were used to evaluate associations between dietary intake and urine concentrations. The habitual consumption (FFQ) of total phytoestrogens was 37.56 mg/day. In urine, the higher compounds were naringenin (60.1 µg/L) and enterolactone (41.7 µg/L). Recent intakes (24 h recall) of isoflavones (

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Cross-Sectional Studies; Diet, Healthy; Female; Heart Diseases; Humans; Mexico; Middle Aged; Neoplasms; Nutrition Surveys; Obesity; Overweight; Patient Compliance; Phytoestrogens; Prevalence; Risk

Hypertrophic cardiomyopathy (HCM) is more severe in male than female mice eating a soy-based diet. We sought to determine whether the detrimental effects are mediated by the phytoestrogens present in soy, the mechanism by which phytoestrogens act, and to test whether estrogen modulates the sexually dimorphic phenotype. A soy-free diet (casein based) supplemented with the predominant phytoestrogens in soy, genistein and daidzein, recapitulated the fibrotic, proapoptotic and negative hemodynamic effects of soy in male hearts. As with the soy diet, the hearts of female HCM mice were not negatively affected by the phytoestrogen-containing diet. To determine the role of estrogen in the sex differences mediated by diet in HCM, gonadectomies were performed and estrogen was administered to male and female HCM mice on a casein- or phytoestrogen-supplemented diet. Somewhat surprisingly, estrogen was not protective in male or female mice with HCM and, in fact, was lethal in phytoestrogen-fed male mice with HCM. Because genistein is a potent tyrosine kinase inhibitor and tyrosine kinase inhibition has been associated with cardiotoxicity, we tested its effects in isolated adult cardiac myocytes. Genistein inhibited different tyrosine kinases depending on sex and, in combination with estrogen, resulted in apoptosis only in adult male cardiac myocytes. Finally, we show that phytoestrogens led to distinct programs of gene expression in hearts from males vs. females with HCM, suggesting mechanisms by which males are more sensitive to the detrimental effects of phytoestrogens and females are protected. These results implicate the phytoestrogen genistein in mediating cardiac pathology in males with HCM and, importantly, establish that estrogen is not protective in the setting of HCM.

Topics: Animals; Estrogens; Female; Genistein; Heart; Heart Diseases; Male; Myocardium; Phytoestrogens; Sex Factors

Topics: Adult; Aged; Breast Neoplasms; Clinical Trials as Topic; Complementary Therapies; Culture; Estrogens; Fear; Female; Heart Diseases; Hormone Replacement Therapy; Humans; Longevity; Menopause; Middle Aged; Osteoporosis, Postmenopausal; Perimenopause; Phytoestrogens; Phytotherapy; Progestins; Risk Assessment; Women's Health

Epidemiological evidence suggests a reduction in the incidence of coronary heart disease, cancer and osteoporosis in populations with a high dietary intake of plant estrogen or phytoestrogen. The clinical benefit of phytoestrogens in cereals, vegetables and medicinal plants is attracting increasing attention for the general public. In the present study, we examined the effect of phytoestrogenic isoflavones daidzein and genistein on glucose toxicity-induced cardiac mechanical malfunction simulating diabetic cardiomyopathy. Adult rat ventricular myocytes were isolated and maintained for 24 hours in normal (NG, 5.5 mM) or high glucose (HG, 25.5 mM) medium in the absence or presence of isoflavones daidzein (50 microM) or genistein (20 microM). Cardiac contractile indices were evaluated using an IonOptix MyoCam system including peak shortening (PS), maximal velocity of shortening/relengthening (+/- dL/dt), time-to-PS (TPS) and time-to-90% relengthening (TR90). Myocytes maintained in HG medium displayed altered mechanical function simulating in vivo diabetes including reduced PS, +/- dL/dt and prolonged TR90 associated with normal TPS compared to those from NG myocytes. Interestingly, these HG-induced mechanical dysfunctions were abolished by co-incubation of daidzein or genistein. However, daidzein but not genistein itself depressed PS in NG myocytes. Neither daidzein nor genistein affected any other mechanical parameters tested in NG myocytes. Collectively, these data suggest that the phytoestrogenic isoflavones daidzein and genistein may reduce glucose toxicity-induced cardiac mechanical dysfunction and thus possess therapeutic potential against diabetes-associated cardiac defects.

Topics: Animals; Cells, Cultured; Genistein; Glucose; Heart Diseases; Heart Ventricles; Isoflavones; Male; Myocardial Contraction; Myocytes, Cardiac; Phytoestrogens; Rats; Rats, Sprague-Dawley

Resveratrol and trans-resveratrol are powerful phytoestrogens, present in the skins of grapes and other plant foods and wine, which demonstrate a broad spectrum of pharmacological and therapeutic health benefits. Phytoestrogens are naturally occurring plant-derived nonsteroidal compounds that are functionally and structurally similar to steroidal estrogens, such as estradiol, produced by the body. Various studies, reviewed herein, have demonstrated the health benefits of phytoestrogens in addressing climacteric syndrome including vasomotor symptoms and postmenopausal health risks, as well as their anticarcinogenic, neuroprotective and cardioprotective activities and prostate health and bone formation promoting properties. Conventional HRT drugs have been demonstrated to cause serious adverse effects including stroke and gallbladder disease, as well as endometrial, uterine and breast cancers. Recent research demonstrates that trans-resveratrol binds to human estrogen receptors and increases estrogenic activity in the body. We investigated the effects of protykin, a standardized extract of trans-resveratrol from Polygonum cuspidatum, on cardioprotective function, the incidence of reperfusion-induced arrhythmias and free radical production in isolated ischemic/reperfused rat hearts. The rats were orally treated with two different daily doses of protykin for 3 weeks. Coronary effluents were measured for oxygen free radical production by electron spin resonance (ESR) spectroscopy in treated and drug-free control groups. In rats treated with 50 and 100 mg/kg of protykin, the incidence of reperfusion-induced ventricular fibrillation was reduced from its control value of 83% to 75% (p < 0.05) and 33% (p < 0.05), respectively. Protykin was seen to possess cardioprotective effects against reperfusion-induced arrhythmias through its ability to reduce or remove the reactive oxygen species in ischemic/reperfused myocardium. Taken together, these data suggest that trans-resveratrol supplementation may be a potential alternative to conventional HRT for cardioprotection and osteoporosis prevention and may confer other potential health benefits in women.

Topics: Animals; Anthocyanins; Anticarcinogenic Agents; Antioxidants; Dose-Response Relationship, Drug; Estrogens, Non-Steroidal; Female; Free Radicals; Heart Diseases; Humans; Isoflavones; Phytoestrogens; Plant Preparations; Proanthocyanidins; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Resveratrol; Stilbenes; Ventricular Fibrillation