Dietary Phytoestrogens Research Articles

Effects of Mixed Pasture Legume Phytoestrogens on Superovulatory Response and Embryo Quality in Angus Cows.

Ovulation and artificial insemination rates have been observed to decrease in sheep and cows when exposed to dietary phytoestrogens at concentrations greater than 25 mg/kg DM. A grazing trial was undertaken to investigate the effects of coumestrol and other key phytoestrogens on the superovulatory response, embryo numbers and quality in beef cows grazing legume pastures. A 7-week controlled grazing trial was conducted with legume and ryegrass pasture treatments, with cows exposed to legumes at two timed treatments, 4 and 7 weeks. Twenty Angus cows were subjected to a conventional estrus synchronization and superovulation protocol. Embryos were recovered via conventional uterine body flushing 7 days post artificial insemination (AI). Numerous phytoestrogens were identified in both pasture and plasma samples, including coumestrol and formononetin. Concentrations of phytoestrogens in the pasture ranged from 0.001 to 47.5 mg/kg DM and 0 to 2.6 ng/mL in plasma. Approximately 50% of cows produced viable embryos 7 days post AI. A significant interaction between the effect of treatment groups on the embryo stage was observed (p < 0.05). The results suggest that concentrations of >25 mg/kg DM of phytoestrogens less than 20 days preceding AI may negatively affect oocyte developmental competence, reduce progesterone production and thus contribute to early embryonic loss.

Dietary phytoestrogen intake and ovarian cancer risk: a prospective study in the prostate, lung, colorectal and ovarian (PLCO) cohort.

Estrogen plays a crucial role in ovarian tumorigenesis. Phytoestrogens (PEs) are a type of daily dietary nutrient for humans and possess a mild estrogenic characteristic. This study aimed to assess the correlation of the consumption of dietary PEs with ovarian cancer risk using data in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Participants were enrolled in PLCO from 1993 to 2001. Hazard ratios (HR) and 95% confidence intervals (CI) were utilized to determine the association between the intake of PEs and ovarian cancer occurrence, which were calculated by the Cox proportional hazards regression analysis. In total, 24 875 participants were identified upon completion of the initial dietary questionnaire (DQX). Furthermore, the analysis also included a total of 45 472 women who filled out the diet history questionnaire (DHQ). Overall, after adjustment for confounders, the dietary intake of total PEs was significantly associated with the risk of ovarian cancer in the DHQ group (HRQ4vsQ1 = 0.69, 95% CI: 0.50-0.95; P for trend = 0.066). Especially, individuals who consumed the highest quartile of isoflavones were found to have a decreased risk of ovarian cancer in the DHQ group (HRQ4vsQ1 = 0.68, 95% CI: 0.50-0.94; P for trend = 0.032). However, no such significant associations were observed for the DQX group. In summary, this study suggests that increased dietary intake of total PEs especially isoflavones was linked with a lower risk for developing ovarian cancer. More research is necessary to validate the findings and explore the potential mechanisms.

From Gut to Hormones: Unraveling the Role of Gut Microbiota in (Phyto)Estrogen Modulation in Health and Disease.

The human gut microbiota regulates estrogen metabolism through the "estrobolome," the collection of bacterial genes that encode enzymes like β-glucuronidases and β-glucosidases. These enzymes deconjugate and reactivate estrogen, influencing circulating levels. The estrobolome mediates the enterohepatic circulation and bioavailability of estrogen. Alterations in gut microbiota composition and estrobolome function have been associated with estrogen-related diseases like breast cancer, enometrial cancer, and polycystic ovarian syndrome (PCOS). This is likely due to dysregulated estrogen signaling partly contributed by the microbial impacts on estrogen metabolism. Dietary phytoestrogens also undergo bacterial metabolism into active metabolites like equol, which binds estrogen receptors and exhibits higher estrogenic potency than its precursor daidzein. However, the ability to produce equol varies across populations, depending on the presence of specific gut microbes. Characterizing the estrobolome and equol-producing genes across populations can provide microbiome-based biomarkers. Further research is needed to investigate specific components of the estrobolome, phytoestrogen-microbiota interactions, and mechanisms linking dysbiosis to estrogen-related pathology. However, current evidence suggests that the gut microbiota is an integral regulator of estrogen status with clinical relevance to women's health and hormonal disorders.

Anticancer and anti-metastasis activity of 1,25 dihydroxycholecalciferols and genistein in MCF-7 and MDA-MB-231 breast cancer cell lines

A powerful steroid hormone precursor, 1,25 dihydroxycholecalciferols (1,25(OH)2D3), and dietary phytoestrogen (genistein) are essential compounds that act by binding to nuclear receptors and altering gene expression. They have many biological benefits, some of which have anticancer properties. We studied the impact of 1,25(OH)2D3 and genistein on the proliferation, progression, and metastasis of MCF-7 and MDA-MB-231 cells when they were used alone or in combination and investigated whether there was a synergistic effect between genistein and 1,25(OH)2D3. To achieve these goals, a variety of assays, including flow cytometry, cell invasion assays, cell adhesion assays, Western blotting, and RT‒PCR, were used.Our findings showed that genistein, 1,25(OH)2D3, and the two combined all effectively declined the growth of MCF-7 and MDA-MB-231 cells by arresting the cells in the G0/G1 phase and inducing an apoptotic pathway. Stimulation of apoptosis was achieved by upregulating the expression of BAX and CASP3 genes and downregulating the expression levels of BCL-2 gene. Furthermore, both compounds suppress metastasis by reducing cell adhesion and cell migration/invasion by elevating the expression level of E-cadherin and reducing the expression level of P-cadherin and N-cadherin. Additionally, both genistein and 1,25(OH)2D3 increased the expression level of ERK1 and reduced the expression levels of JNK, p38, Ras, and MEK proteins, which reduced metastasis, enhanced the response to cancer treatment, and improved overall survival. Thus, genistein and 1,25(OH)2D3 can both be considered key candidates in the search for new breast cancer treatments.

Diet-microbiome-immune interplay in multiple sclerosis: Understanding the impact of phytoestrogen metabolizing gut bacteria.

Multiple sclerosis (MS) is a chronic and progressive autoimmune disease of the central nervous system (CNS), with both genetic and environmental factors contributing to the pathobiology of the disease. Although HLA genes have emerged as the strongest genetic factor linked to MS, consensus on the environmental risk factors is lacking. Recently, the gut microbiota has garnered increasing attention as a potential environmental factor in MS, as mounting evidence suggests that individuals with MS exhibit microbial dysbiosis (changes in the gut microbiome). Thus, there has been a strong emphasis on understanding the role of the gut microbiome in the pathobiology of MS, specifically, factors regulating the gut microbiota and the mechanism(s) through which gut microbes may contribute to MS. Among all factors, diet has emerged to have the strongest influence on the composition and function of gut microbiota. As MS patients lack gut bacteria capable of metabolizing dietary phytoestrogen, we will specifically discuss the role of a phytoestrogen diet and phytoestrogen metabolizing gut bacteria in the pathobiology of MS. A better understanding of these mechanisms will help to harness the enormous potential of the gut microbiota as potential therapeutics to treat MS and other autoimmune diseases.

An Overview on Phytoestrogen based antihypertensive agent for their potential Pharmacological Mechanism

Recent studies shown that the data of clinical, experimental and epidemiological studies indicates that dietary phytoestrogens, flavonoids and polyphenolic compounds have shown most potent activities for prevention in CVDs. The major class of compounds found in phytoestrogen. These phytoestrogens are sub-classified into coumestans, prenylflavonoids and isoflavones. These class having the most active class in estrogenic effects, polyphenols (also known as polyhydroxyphenols includes tannic acid, ellagitannin. These studies also indicate that dietary supplements and food nutrients have profound cardioprotective effects in the primary as well as secondary coronary heart disease and hence they are considered as cardiovascular friendly natural products. The mechanism of cardioprotection produced by dietary nutritional supplements such as phytoestrogens (soy and soy protein), flavonoids (citrus fruits, pulses, red wine, tea and cocoa), olive oil, omega-3 fatty acids (fish oil and fish-based products), lycopene (tomato and tomato-based products), resveratrol (grapes and red wine), coffee, and soy in the prevention and treatment of cardiovascular disorders have been discussed in the following review (in parenthesis) with the emphasis of epidemiological and clinical studies. Based on the intriguing results of various studies, prophylactic and therapeutic potential of cardiovascular friendly natural products have been suggested.

Insight into the Potential Mechanisms of Endocrine Disruption by Dietary Phytoestrogens in the Context of the Etiopathogenesis of Endometriosis.

Phytoestrogens (PEs) are estrogen-like nonsteroidal compounds derived from plants (e.g., nuts, seeds, fruits, and vegetables) and fungi that are structurally similar to 17β-estradiol. PEs bind to all types of estrogen receptors, including ERα and ERβ receptors, nuclear receptors, and a membrane-bound estrogen receptor known as the G protein-coupled estrogen receptor (GPER). As endocrine-disrupting chemicals (EDCs) with pro- or antiestrogenic properties, PEs can potentially disrupt the hormonal regulation of homeostasis, resulting in developmental and reproductive abnormalities. However, a lack of PEs in the diet does not result in the development of deficiency symptoms. To properly assess the benefits and risks associated with the use of a PE-rich diet, it is necessary to distinguish between endocrine disruption (endocrine-mediated adverse effects) and nonspecific effects on the endocrine system. Endometriosis is an estrogen-dependent disease of unknown etiopathogenesis, in which tissue similar to the lining of the uterus (the endometrium) grows outside of the uterus with subsequent complications being manifested as a result of local inflammatory reactions. Endometriosis affects 10-15% of women of reproductive age and is associated with chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. In this review, the endocrine-disruptive actions of PEs are reviewed in the context of endometriosis to determine whether a PE-rich diet has a positive or negative effect on the risk and course of endometriosis.

Hepatotoxic effect of dietary phytoestrogens on juvenile cultured Russian sturgeon (Acipenser gueldenstaedtii)

In the last two decades, much controversy has grown over the use of soybean products in aquafeeds, especially for carnivorous fish like sturgeons. One point of discussion is the effect of soybean phytoestrogens on fish health. There are many aspects of phytoestrogen utilization in aquafeeds, therefore, the aim of this study is to verify if common legume phytoestrogens can affect juvenile cultured sturgeon erythrocyte and hepatocyte genotoxicity and cause liver pathology. Russian sturgeons were fed from 100 till 365 dph11Days post hutching. with daidzein, genistein, and coumestrol supplemented diets in concentrations: 10, 0.05 and 0.001 g kg−1 of feed, respectively. The SCGE22Single Cell Gel Electrophoresis (comet assay). method combined with qPCR of three genes involved in DNA repair and genome maintenance, namely cyp1a1, gaad45a and p53 were analyzed. The results were compared with histopathological evaluation of liver tissue. In fish fed with coumestrol supplemented diet, DNA strand damage was the highest in both erythrocytes and hepatocytes, however, simultaneously the lowest level of oxidative DNA damage was found. Additionally, slightly elevated expression of the p53 gene was observed along with a decreased number of apoptotic hepatocytes, which suggests that low concentration of coumestrol may support DNA repair mechanisms in the liver. Although, daidzein showed a preventive effect only against fibrosis. Isoflavones did not show a significant effect on DNA damage in studied cells. Genistein was found to increase macro- and microvesicular steatosis, portal hepatitis and fibrosis, indicating its negative role in the development of liver injuries. Daidzein alleviated some sturgeon liver damage, especially macrovesicular steatosis and interface hepatitis. However, it increased hepatocyte apoptosis, which may suggest daidzein potentially inducing liver injury, though not manifested by other histopathological lesions. Therefore, it can be concluded that at given concentrations, the tested phytoestrogens did not show clearly hepatoprotective effect in sturgeons.

Dysregulation of Immature Sertoli Cell Functions by Exposure to Acetaminophen and Genistein in Rodent Cell Models.

Sertoli cells are essential for germ cell development and function. Their disruption by endocrine disrupting chemicals (EDCs) or drugs could jeopardize spermatogenesis, contributing to male infertility. Perinatal exposure to EDCs and acetaminophen (APAP) disrupts male reproductive functions in animals and humans. Infants can be exposed simultaneously to the dietary soy phytoestrogen genistein (GEN) and APAP used for fever or pain relief. Our goal was to determine the effects of 10-100 µM APAP and GEN, alone or mixed, on immature Sertoli cells using mouse TM4 Sertoli cell line and postnatal-day 8 rat Sertoli cells, by measuring cell viability, proliferation, prostaglandins, genes and protein expression, and functional pathways. A value of 50 µM APAP decreased the viability, while 100 µM APAP and GEN decreased the proliferation. Sertoli cell and eicosanoid pathway genes were affected by GEN and mixtures, with downregulation of Sox9, Cox1, Cox2, and genes relevant for Sertoli cell function, while genes involved in inflammation were increased. RNA-seq analysis identified p53 and TNF signaling pathways as common targets of GEN and GEN mixture in both cell types. These results suggest that APAP and GEN dysregulate immature Sertoli cell function and may aid in elucidating novel EDC and drug targets contributing to the etiology of male infertility.

Phytoestrogens Present in Follicular Fluid and Urine Are Positively Associated with IVF Outcomes following Single Euploid Embryo Transfer

The impact and safety of phytoestrogens, plant-derived isoflavones with estrogenic activity predominantly present in soy, on female reproductive health and IVF outcomes continues to be hotly debated. In this prospective cohort study, 60 women attending IVI-RMA New Jersey undergoing IVF with single frozen embryo transfer (SET/FET) of good-quality euploid blastocyst after PGT-A analysis were recruited. Concentrations of two phytoestrogens (daidzein and genistein) in follicular fluid (FF) and urine (U) were measured by UPLC–MSMS, both collected on vaginal oocyte retrieval day. These measurements correlated with IVF clinical outcomes. In models adjusted for age, BMI, race/ethnicity, and smoking status, higher FF phytoestrogen concentrations were significantly associated with higher serum estradiol, enhanced probability of implantation, clinical pregnancy, and live birth. Moreover, higher urine phytoestrogen concentrations were significantly associated with improved oocyte maturation and fertilization potential and increased probability of clinical pregnancy and live birth. Finally, higher FF and urine phytoestrogen concentrations were associated with a higher probability of live birth from a given IVF cycle. Our results suggest that dietary phytoestrogens improved reproductive outcomes of women undergoing IVF treatment. However, additional prospective studies are needed to optimize the use of phytoestrogens to further enhance reproductive outcomes and/or protect against reproductive insults.

Natural products and Hypertension: Scope and role in Antihypertensive Therapy

Recent studies shown that the data of clinical, experimental and epidemiological studies indicates that dietary phytoestrogens, flavonoids and polyphenolic compounds have shown most potent activities for prevention in CVDs. The major class of compounds found in phytoestrogen. These phytoestrogens are sub-classified into coumestans, prenylflavonoids and isoflavones. These class having the most active class in estrogenic effects, polyphenols (also known as polyhydroxyphenols includes tannic acid, ellagitannin. These studies also indicate that dietary supplements and food nutrients have profound cardioprotective effects in the primary as well as secondary coronary heart disease and hence they are considered as cardiovascular friendly natural products. The mechanism of cardioprotection produced by dietary nutritional supplements such as phytoestrogens (soy and soy protein), flavonoids (citrus fruits, pulses, red wine, tea and cocoa), olive oil, omega-3 fatty acids (fish oil and fish-based products), lycopene (tomato and tomato-based products), resveratrol (grapes and red wine), coffee, and soy in the prevention and treatment of cardiovascular disorders have been discussed in the following review (in parenthesis) with the emphasis of epidemiological and clinical studies. Based on the intriguing results of various studies, prophylactic and therapeutic potential of cardiovascular friendly natural products have been suggested.

Dietary phytoestrogen diosgenin interrupts metabolism, physiology, and reproduction of Swiss albino mice: Possible mode of action as an emerging environmental contaminant, endocrine disruptor and reproductive toxicant.

Dietary phytoestrogens are the main source of environmental contamination due to their estrogen-mimicking and endocrine-disrupting effects, posing a threat to microbial, soil, plant, and animal health. Diosgenin, a phytosteroid saponin, is used in many traditional medicines, nutraceuticals, dietary supplements, contraceptives, and hormone replacement therapies against numerous diseases and disorders. It is important to be aware of the potential risks associated with diosgenin, as well as its potential to cause reproductive and endocrine toxicity. Due to the lack of research on the safety and probable adverse side effects of diosgenin, this work evaluated the endocrine-disrupting and reproductive toxicity of diosgenin in albino mice by following acute toxicity (OECD-423), repeated dose 90-day oral toxicity (OECD-468), and F1 extended one-generation reproductive toxicity (OECD-443) studies. Diosgenin was found to be slightly toxic, with LD50 for male and female mice being 546.26 and 538.72 mg/kg, respectively. Chronic exposure of diosgenin (10, 50, 100, and 200 mg/kg) generated oxidative stress, depleted antioxidant enzymes, disturbed homeostasis of the reproductive hormones, and interrupted steroidogenesis, germ cell apoptosis, gametogenesis, sperm quality, estrous cycle, and reproductive performance in the F0 and F1 offspring. Long-term oral exposure of diosgenin to the mice disturbed the endocrine and reproductive functions and generated transgenerational reproductive toxic effects in F0 and F1 offspring. These results suggest that diosgenin should be used carefully in food products and medical applications due to its potential endocrine-disrupting and reproductive toxic effects. The findings of this study provide a better understanding of the potential adverse effects of diosgenin and the need for appropriate risk assessment and management of its use.

Mitochondria-targeted derivative of pterostilbene, a dietary phytoestrogen, exhibits superior cancer cell cytotoxicity via mitochondrial superoxide mediated induction of autophagy

Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene;PTS), a dimethyl ether analogue of resveratrol, has been shown to possess anti-bacterial, anti-cancer, anti-inflammatory and antioxidant properties. In the present study, we have synthesized a mitochondria targeted derivative of Pterostilbene (M-PTS) with aim to enhance its anti-cancer efficacy. M-PTS was synthesized by substituting the free hydroxyl group of PTS with a propyl linker and Triphenylphosphonium (TPP+, a membrane-permeable lipophilic cation that readily accumulates and penetrates through the mitochondrial membrane). We observed that mitochondrial uptake of M-PTS in A549 cells was higher (∼8.5-fold) as compared to PTS and M-PTS was more potent in killing human lung (A549) and breast (MCF-7) cancer cells as compared to PTS. IC50 of M-PTS was found to be 0.17 µM and 0.76 µM, respectively, while IC50 of PTS was found to be 40.45 µM and 53.15 µM in A549 and MCF-7 cells, respectively. M-PTS was superior in inhibiting the clonogenic potential of A549 and MCF-7 cell and M-PTS induced apoptosis in A549 cells. M-PTS specifically increased both cytosolic ROS and mitochondrial superoxide levels whereas PTS did not have any effect on mitochondrial superoxide. M-PTS treatment led to autophagy induction in cancer cells. M-PTS induced cytotoxicity was attenuated on pre-treatment with mitochondria-targeted antioxidant (mitoTEMPO) as well as inhibitor of autophagy (chloroquine) signifying the involvement of mitochondrial ROS and autophagy in the cytotoxic effects of M-PTS. In conclusion, the superior cytotoxic efficacy of M-PTS via specific induction of mitochondrial superoxide illustrates the application of mitochondria targeted redox-active natural products as potent anti-cancer drugs.

Endocrine Disruptors in Food, Estrobolome and Breast Cancer.

The microbiota is now recognized as one of the major players in human health and diseases, including cancer. Regarding breast cancer (BC), a clear link between microbiota and oncogenesis still needs to be confirmed. Yet, part of the bacterial gene mass inside the gut, constituting the so called "estrobolome", influences sexual hormonal balance and, since the increased exposure to estrogens is associated with an increased risk, may impact on the onset, progression, and treatment of hormonal dependent cancers (which account for more than 70% of all BCs). The hormonal dependent BCs are also affected by environmental and dietary endocrine disruptors and phytoestrogens which interact with microbiota in a bidirectional way: on the one side disruptors can alter the composition and functions of the estrobolome, ad on the other the gut microbiota influences the metabolism of endocrine active food components. This review highlights the current evidence about the complex interplay between endocrine disruptors, phytoestrogens, microbiome, and BC, within the frames of a new "oncobiotic" perspective.

Effects on Serum Hormone Concentrations after a Dietary Phytoestrogen Intervention in Patients with Prostate Cancer: A Randomized Controlled Trial.

Phytoestrogens have been suggested to have an anti-proliferative role in prostate cancer, potentially by acting through estrogen receptor beta (ERβ) and modulating several hormones. We primarily aimed to investigate the effect of a phytoestrogen intervention on hormone concentrations in blood depending on the ERβ genotype. Patients with low and intermediate-risk prostate cancer, scheduled for radical prostatectomy, were randomized to an intervention group provided with soybeans and flaxseeds (∼200 mg phytoestrogens/d) added to their diet until their surgery, or a control group that was not provided with any food items. Both groups received official dietary recommendations. Blood samples were collected at baseline and endpoint and blood concentrations of different hormones and phytoestrogens were analyzed. The phytoestrogen-rich diet did not affect serum concentrations of testosterone, insulin-like growth factor 1, or sex hormone-binding globulin (SHBG). However, we found a trend of decreased risk of increased serum concentration of estradiol in the intervention group compared to the control group but only in a specific genotype of ERβ (p = 0.058). In conclusion, a high daily intake of phytoestrogen-rich foods has no major effect on hormone concentrations but may lower the concentration of estradiol in patients with prostate cancer with a specific genetic upset of ERβ.

Serum Acetate:Propionate Ratio Is Related to Serum Cholesterol in Men but Not Women

Acetic and propionic acids, produced by colonic fermentation of unabsorbed carbohydrates, may influence systemic lipid metabolism. To determine whether the ratio of the concentrations of acetate to propionate in peripheral serum of fasting humans was related to serum cholesterol, we studied 62 men [age 45 ± 17 y (mean ± SD), range 19–74 y; body mass index 25.0 ± 2.8 kg/m2] and 69 women [43 ± 18 y, (range, 18–77 y); body mass index 23.0 ± 3.1 kg/m2] with normal serum lipid concentrations. The concentrations of serum acetate, propionate and buty-rate (means ± SD) were similar in men (98 ± 33, 3.8 ± 1.5 and 2.3 ± 1.5 µmol/L, respectively) and women (92 ± 38, 3.9 ± 1.9 and 2.3 ± 1.6 µmol/L). There were significant positive relationships between the serum acetate:propionate ratio and total cholesterol (r = 0.466, P = 0.0002) and LDL cholesterol (r = 0.384, P = 0.0023) in men, but in women the relationships were not significant (R = 0.174, P = 0.15 and r = 0.135, P = 0.27, respectively). The relationships in men remained significant after adjustment for age and body mass index. These data support the hypothesis that, at least in men, colonic short-chain fatty acids influence systemic lipid metabolism. The relationships among the factors influencing colonic short-chain fatty acid production, the enterohepatic circulation of endogenous estrogens, dietary phytoestrogens and blood lipids in women, however, need further clarification.

Low-moderate dietary phytoestrogens transiently disrupt spermatogenesis and the seminal plasma proteome in the ram.

Dietary phytoestrogens disrupt a specific stage of ram spermatogenesis, causing subtle decreases in sperm quality by affecting the expression of pathways involved in the structural integrity of the spermatozoa. This paper demonstrates for the first time that ram reproduction is compromised by oestrogenic pasture, whilst also providing a longitudinal model for the impact of phytoestrogens on male fertility. Compounds with oestrogen-like actions are now common in both the Western diet. The long-term impacts and underlying mechanisms by which oestrogenic compounds alter male reproduction, however, are unclear. To investigate this, we used a longitudinal sheep model examining the impact of oestrogenic pasture consumption on semen quality and production, testicular size, sexual behaviour and the seminal plasma proteome of Merino rams (n = 20), over a full spermatogenic cycle and in the subsequent breeding season. Throughout the study period, sexual behaviour, sperm production and motility were similar between the exposed and non-exposed rams (P > 0.05). However, between 5 and 8 weeks of exposure to dietary phytoestrogens, rams produced a higher percentage of spermatozoa with a specific malformation of the sperm midpiece and reduced DNA integrity, compared to non-exposed rams (P < 0.001). Investigation into the seminal plasma proteome revealed 93 differentially expressed proteins between phytoestrogen-exposed and control rams (P < 0.05). Exposure to phytoestrogens increased the expression of proteins involved in cellular structure development, actin cytoskeleton reorganisation, regulation of cell function and decreased expression in those related to catabolic processes. The greatest fold changes were in proteins involved in the assembly of the sperm flagella, removal of cytoplasm, spermatid development and maintenance of DNA integrity. After returning to non-oestrogenic pasture, no differences in any measure were observed between treatment groups during the subsequent breeding season. We conclude that dietary phytoestrogens can transiently disrupt specific stages of ram spermatogenesis, causing subtle decreases in sperm quality by affecting the expression of pathways involved in the structural integrity of the spermatozoa.

THE ROLE OF NUTRITION AND BIOACTIVE SUBSTANCES OF PLANT ORIGIN IN THE PREVENTION OF CANCER DISEASES

Background. Cancer is one of the leading causes of mortality worldwide. Carcinogenesis is a multistage and complex process that may be partially reversible. In the process of carcinogenesis, numerous metabolic pathways associated with normal cell growth and division are disturbed. An important role in the prevention of cancer is played by a lifestyle characterized by maintaining a healthy weight, an appropriate level of physical activity and increased consumption of food with anti-cancer properties. Results and conclusion. The paper presents the latest literature reports on the pathogenesis of cancer and the impact of diet on the risk of its occurrence. In addition, known models of carcinogenesis and their impact on the development of knowledge in the field of oncology are discussed. Current recommendations on nutrition in cancer prevention, developed by the American Cancer Research Fund, are also presented. The aim of this paper is also to present the role of selected bioactive components of plant origin in cancer prevention. The paper presents basic information on carcinogenesis and the dietary anticancerogen mechanisms . Individual groups of bioactive compounds showing anticancer activity are discussed: dietary fiber, phenolic compounds, flavonoid phytoestrogens (classified as phenolic compounds) and nonflavonoid compounds, betalains, glucosinolates, phytates and carotenoids. An attempt was made to systematize knowledge on the anticancer properties of these compounds. By altering the diet, the supply of plant-derived bioactive components should be increased, which, through various mechanisms, have the ability to inhibit various phases of tumor formation and reduce the supply of potential carcinogens.

Dietary phytoestrogens and total and cause-specific mortality: results from 2 prospective cohort studies

BackgroundEvidence regarding dietary phytoestrogens in relation to mortality remains limited. ObjectivesThe objective of the study is to examine the associations of intake of isoflavones, lignans, and coumarins with total and cause-specific mortality in US males and females. MethodsWe followed 75,981 females in the Nurses’ Health Study (1984–2018) and 44,001 males in the Health Professionals Follow-up Study (1986–2018), who were free of cardiovascular disease (CVD), diabetes, or cancer at baseline. Their diet was repeatedly assessed using validated food frequency questionnaires every 2–4 y. Associations with mortality were assessed using time-dependent Cox models with adjustments for demographics, dietary and lifestyle factors, and medical history. ResultsDuring 3,427,156 person-years of follow-up, we documented 50,734 deaths, including 12,492 CVD deaths, 13,726 cancer deaths, and 24,516 other non-CVD and noncancer deaths. After multivariable adjustment, the higher total phytoestrogen intake was associated with lower risk of total CVD and other non-CVD and noncancer mortality: comparing extreme quintiles, the pooled HRs (95% CIs) were 0.89 (0.87, 0.92), 0.90 (0.85, 0.96), and 0.86 (0.82, 0.90), respectively. We did not find a significant association with cancer mortality [0.97 (0.92, 1.03)]. For individual phytoestrogens in relation to total mortality, the pooled HRs (95% CIs) comparing extreme quintiles were 0.90 (0.87, 0.92) for isoflavones, 0.93 (0.90, 0.96) for lignans, and 0.93 (0.90, 0.95) for coumarins. Individual phytoestrogens were also significantly associated with lower risk of CVD mortality and other types of mortality. Primary food sources of phytoestrogens, including tofu, soy milk, whole grains, tea, and flaxseed, were also inversely associated with total mortality. ConclusionsA higher intake of total phytoestrogens, including isoflavones, lignans, and coumarins, and foods rich in these compounds was associated with lower risk of total and certain cause-specific mortality in generally healthy US adults. These data suggest that these phytochemicals and their dietary sources may be integrated into an overall healthy diet to achieve a longer life span.

Anti-allergic property of dietary phytoestrogen secoisolariciresinol diglucoside through microbial and β-glucuronidase-mediated metabolism

Phytoestrogens play pivotal roles in controlling not only the endocrine system but also inflammatory metabolic disorders. However, the effects of dietary phytoestrogens on allergic diseases and underlying mechanisms remain unclear. In this study, we revealed the unique metabolic conversion of phytoestrogen to exert anti-allergic properties, using an ovalbumin-induced allergic rhinitis mouse model. We found that dietary secoisolariciresinol diglucoside (SDG), a phytoestrogen abundantly present in flaxseed, alleviated allergic rhinitis by the microbial conversion to enterodiol (ED). We also found that ED circulated mainly in the glucuronide form (EDGlu) in blood, and deconjugation of EDGlu to ED aglycone occurred in the nasal passage; this activity was enhanced after the induction of allergic rhinitis, which was mediated by β-glucuronidase. We further found that IgE-mediated degranulation was inhibited by ED aglycone, but not by EDGlu, in a G protein-coupled receptor 30 (GPR30)-dependent manner. These results provide new insights into the anti-allergic properties of phytoestrogens and their metabolism in vivo for the development of novel therapeutic strategies against allergic rhinitis.