The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: A randomized, double-blind, crossover study

Context: There is concern whether soy phytoestrogens may affect thyroid function. If true, soy phytoestrogens may be expected to have a greater impact in subjects with subclinical hypothyroidism. Objective: The primary aim was to determine the effect of soy phytoestrogen supplementation on thyroid function, with a secondary aim of assessing the effects on cardiovascular risk indices in patients with subclinical hypothyroidism. Design and Setting: We conducted a randomized, double-blind, crossover study in a tertiary care setting. Participants: Sixty patients with subclinical hypothyroidism participated in the study. Intervention: Patients were randomly assigned to either low-dose phytoestrogen (30 g soy protein with 2 mg phytoestrogens, representative of a Western diet) or high-dose phytoestrogen (30 g soy protein with 16 mg phytoestrogens, representative of a vegetarian diet) supplementation for 8 wk, then crossed over after an 8-wk washout period. Main Outcome Measures: The primary outcome was progression to overt hypothyroidism, with secondary outcome measures of blood pressure, insulin resistance, lipids, and highly sensitive C-reactive protein (hsCRP). Results: Six female patients in the study progressed into overt hypothyroidism with a standardized rate ratio of 3.6 (95% confidence interval, 1.9, 6.2) after 16-mg phytoestrogen supplementation. Both systolic and diastolic blood pressure decreased with 16 mg phytoestrogens, whereas systolic pressure alone decreased with 2 mg phytoestrogens. Insulin resistance (homeostasis model assessment of insulin resistance, 3.5 ± 0.09 vs. 2.6 ± 0.08; P < 0.02) and hsCRP (4.9 ± 0.04 vs. 3.9 ± 0.03; P < 0.01) decreased with 16 mg phytoestrogens. Lipid profile remained unchanged. Conclusion: There is a 3-fold increased risk of developing overt hypothyroidism with dietary supplementation of 16 mg soy phytoestrogens with subclinical hypothyroidism. However, 16-mg soy phytoestrogen supplementation significantly reduces the insulin resistance, hsCRP, and blood pressure in these patients. Copyright © 2011 by The Endocrine Society

Phytoestrogens

Collectively, plants contain several different families of natural products among which are compounds with weak estrogenic or antiestrogenic activity toward mammals. These compounds, termed phytoestrogens, include certain isoflavonoids, flavonoids, stilbenes, and lignans. The best-studied dietary phytoestrogens are the soy isoflavones and the flaxseed lignans. Their perceived health beneficial properties extend beyond hormone-dependent breast and prostate cancers and osteoporosis to include cognitive function, cardiovascular disease, immunity and inflammation, and reproduction and fertility. In the future, metabolic engineering of plants could generate novel and exquisitely controlled dietary sources with which to better assess the potential health beneficial effects of phytoestrogens

Reference Profile Correlation Reveals Estrogen-like Trancriptional Activity of Curcumin

Background: Several secondary metabolites from herbal nutrient products act as weak estrogens (phytoestrogens), competing with endogenous estrogen for binding to the estrogen receptors and inhibiting steroid converting enzymes. However, it is still unclear whether these compounds elicit estrogen dependent transcription of genes at physiological concentrations. Methods: We compare the effects of physiological concentrations (100 nM) of the two phytoestrogens Enterolactone and Quercetin and the suspected phytoestrogen Curcumin on gene expression in the breast cancer cell line MCF7 with the effects elicited by 17-beta-estradiol (E2). Results: All three phytocompounds have weak effects on gene transcription; most of the E2 genes respond to the phytoestrogens in the same direction though to a much lesser extent and in the order Curcumin > Quercetin > Enterolactone. Gene regulation induced by these compounds was low for genes strongly induced by E2 and similar to the latter for genes only weakly regulated by the classic estrogen. Of interest with regard to the treatment of menopausal symptoms, the survival factor Birc5/survivin and the oncogene MYBL1 are strongly induced by E2 but only marginally by phytoestrogens. Conclusion: This approach demonstrates estrogenic effects of putative phytoestrogens at physiological concentrations and shows, for the first time, estrogenic effects of Curcumin. Copyright (C) 2010 S. Karger AG, Base

Cellular uptake of soy-derived phytoestrogens in vitro and in human whole blood

Epidemiological studies comparing typical Western and traditional Eastern lifestyles indicate that dietary intake of soyderived phytoestrogens, including genistein, daidzein, and equol, may have significant health protective effects on hormone-dependent cancers, osteoporosis and cardiovascular diseases. Phytoestrogens have been demonstrated to exert varying effects depending on tissue, endogenous hormone concentrations, and receptor types. Thus, a detailed understanding of the biodistribution and bioavailability of specific phytoestrogens is required in order to predict the subsequent biologic activities. In this study we aimed to investigate the cellular uptake of these soy-derived phytoestrogens in different cell types, including the mammary MCF-7/6 and MDAB-MB 231 cell lines, the ovarian Ishikawa Var-I cell lines and in murine adipocyte clusters. Furthermore, the biodistribution between serum and cell fraction was also investigated in human whole blood. Equol generally shows a higher cellular uptake when compared with genistein and daidzein. Therefore, equol may be more potent with respect to its relative bioactivity, which is corroborated by the observations of specific health effects associated with the equol-producer phenotype

Higher usual dietary intake of phytoestrogens is associated with lower aortic stiffness in postmenopausal women

Objective¿ Phytoestrogens have been postulated to protect against cardiovascular diseases, but few studies have focused on the effect of Western dietary phytoestrogen intake. Methods and Results¿ Four hundred three women with natural menopause either between 1987 and 1989 or between 1969 and 1979 were selected from the baseline data of the PROSPECT study (n=17 395). Isoflavone and lignan intake was calculated from a food-frequency questionnaire. Aortic stiffness was noninvasively assessed by pulse-wave velocity measurement of the aorta. Linear regression analysis was used. After adjustment for age, body mass index, smoking, physical activity, mean arterial pressure, follow-up time, energy intake, dietary fiber intake, glucose, and high density lipoprotein cholesterol, increasing dietary isoflavone intake was associated with decreased aortic stiffness: -0.51 m/s (95% CI -1.00 to -0.03, fourth versus first quartile, P for trend=0.07). Increasing dietary intake of lignans was also associated with decreased aortic pulse-wave velocity: -0.42 m/s (95% CI -0.93 to 0.11, fourth versus first quartile, P for trend=0.06). Results were most pronounced in older women: for isoflavones, -0.94 m/s (95% CI -1.65 to -0.22, P for trend=0.02), and for lignans, -0.80 m/s (95% CI -1.85 to -0.05), fourth versus first quartile. Conclusions¿ The results of our study support the view that phytoestrogens have a protective effect on the risk of atherosclerosis and arterial degeneration through an effect on arterial walls, especially among older wome

PhytoMilk

Potential improvement of the salutary effect of organic dairy milk by forage species and by supplementation

The role of Phytoestrogens in the management of menopausal symptoms

Menopause reflects a change in the woman’s physiological hormonal status and is regarded as a pivotal point in a woman’s life. The commonest symptoms experienced by women during the menopause are hot flushes and night sweats. Although HRT remains the gold standard for the treatment of menopausal symptoms, certain controversial studies have led to a shift against the regular use of HRT. Many physicians and women have turned to alternative ‘natural’ products, hoping that these can substitute the need for HRT. The evidence base for the efficacy and safety of phytoestrogens, in particular isoflavones, will be discussed.peer-reviewe

The Association Between Urinary Genistein Levels and Mortality Among Adults in the United States

BackgroundCurrent research on the relationship between phytoestrogens and mortality has been inconclusive. We explored the relationship between genistein, a phytoestrogen, and mortality in a large cohort representative of the United States population.Methods: Data were analyzed from the National Health and Nutrition Examination Survey (NHANES) from 1999–2010. Normalized urinary genistein (nUG) was analyzed as a log-transformed continuous variable and in quartiles. Mortality data were obtained from the National Death Index and matched to the NHANES participants. Survival analyses were conducted using the Kaplan-Meier analysis. Cox proportional hazard models were constructed for all-cause and cause-specific mortality without and with adjustment for potential confounding variables.Results: Of 11,497 participants, 944 died during the 64,443 person-years follow-up. The all-cause mortality rate was significantly lower in the lowest quartile compared to the highest quartile (incidence rate ratio = 2.14, 95%CI = 1.76 to 2.60). Compared to the lowest quartile, the highest quartile had significantly higher adjusted all-cause (HR = 1.57, 95%CI = 1.23 to 2.00), cardiovascular (HR = 1.67, 95%CI = 1.04 to 2.68), and other-cause (HR = 1.85, 95%CI = 1.33 to 2.57) mortality.Conclusion: We found that high urinary genistein levels were associated with increased risk of all-cause, cardiovascular, and other-cause mortality. This is contrary to popular opinion on the health benefits of genistein and needs further research

Androgen receptor expression in the rat prostate is down-regulated by dietary phytoestrogens

BACKGROUND: It is well established that the growth of the prostate gland is a hormone-dependent phenomenon involving both androgenic and estrogenic control. Proliferation of prostate cells is, at least in part, under control of estrogen receptor beta (ER-beta). Phytoestrogens bind ER-beta with high affinity and therefore may have antiproliferative effects in the prostate. METHODS: The prostates of male Long-Evans rats fed a diet high in phytoestrogens (Phyto-600) or very low levels of phytoestrogens (Phyto-free) were analyzed to determine the impact of dietary phytoestrogens on prostate weight and androgen receptor (AR) expression in the prostate. RESULTS: Dietary phytoestrogens significantly decreased post-pubertal prostate weight gain in Phyto-600 vs Phyto-free fed males. Additionally, dietary phytoestrogens (Phyto-600) decreased AR expression in the prostate as determined by in situ hybridization. CONCLUSIONS: Soy phytoestrogens, present in diet, alter prostate growth presumably by binding ER-beta and subsequently reducing AR expression within the prostate