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The relationship of obesity with lifestyle and dietary exposure to endocrine-disrupting chemicals
Abstract
Phytoestrogens are natural components of plants, including numerous foods that form part of the habitual diet of humans and animals. They have similar estrogenic effects to those of synthetic endocrine disrupters such as monomers of plastic materials, e.g., polycarbonates and epoxy resins. The most frequently used monomer is bisphenol A (BPA), which has been found to migrate from drink and food packaging, plastic baby bottles, and the coating of cans. Numerous studies have associated exposure to endocrine disrupters with obesity, classifying them as obesogens. The objectives of this study were to estimate the dietary exposure to phytoestrogens and BPA in a group of Spanish schoolchildren and to estimate their potential obesogenic effects. The diet of this population of healthy Spanish children was estimated to have a mean total estrogenic capacity of 5.10-12 M eq.E2 (5 pmol/day). The effects of this additional estrogenic burden are highly controversial, and no definitive conclusion has been reached. Thus, some authors consider exposure to these substances with estrogenic activity to be positive at certain stages of life, whereas others regard it as posing a risk at any age. In the present population of children, the likelihood of normal weight versus obesity was significantly related to the total proliferative effect (OR = 0.51, p = 0.026) as well as to the energy expenditure on physical activity, with lesser activity implying a greater risk of obesity (OR = 13.54, p = 0.001). Further research is warranted on the obesogenic effects of exposure to endocrine disruptors present in foods.
... As a weak estrogen, isoflavone can compete with the more potent natural endogenous estrogens to act as an anti-estrogen, which has important implications for reducing breast cancer risk. The hormone action of these agents has been known for some time [9][10][11], and estrogenic and/or anti-estrogenic effects have been observed in farm and wild animals, in vivo and in vitro tests, and in humans [3,[12][13][14][15]. In vitro assays have shown the estrogenic agonist activity of certain phytoestrogens at lower concentrations, which stimulate mammary cell proliferation and gene expression of estrogen-dependent genes, whereas at higher concentrations they may antagonize natural hormones [1,[16][17][18]. ...
... We have published many studies on the estrogenic effects of synthetic and natural molecules that are part of food, either as natural components, especially of vegetables, or due to contamination. Most of these molecules have been categorized as endocrine disruptors following analysis of their in vitro or in vivo behavior in biological media [3,15,17,45]. ...
... Our research group has published numerous studies on the estrogenic effects of natural and synthetic molecules in foods, especially vegetables. Many of these molecules have been classified as endocrine disrupters after analyses of their behavior in biological media in vitro or in vivo [3,15,17,45]. ...
Phytoestrogens are components naturally occurring in plants and include many foods that are part of the regular diet of animals and humans. Phytoestrogens are xenoestrogens of plant origin that are not produced in the endocrine system. Phytoestrogens can act as either agonists or antagonists, depending on their tissue concentrations and the levels of endogenous estrogens at various life stages. The aim was to evaluate the intake of phytoestrogens and the estrogenic effect of the diet of women at university in Chihuahua (Mexico). In total, 400 female university students individually filled out a food frequency questionnaire (FFQ) that included 120 foods. Estimates of the intake of phytoestrogen (genistein, daidzein, biochanin A, formononetin, matairesinol, coumestrol, enterolactone, secoisoresinol, enterodiol) in the subjects’ daily diet were based on published reports. Quantification of phytoestrogens was expressed in µg day⁻¹. The estrogenic effect of those compound identified according to the foods consumed was estimated using the in vitro E-SCREN test. SPSS v.22.0 (IBM, Chicago, IL, USA) was applied for statistical analysis following descriptive analysis and stepwise regression. p < 0.050 was taken as significant. The results of intake show that the majority of isoflavones are formononetin (median 110.60 (μg day⁻¹) and their estrogenic activity is 4.11 Eq. E2 (pmol day⁻¹); the majority of lignans are enterolactone (median 147.24 (μg day⁻¹), and their estrogenic activity is 4.94 Eq. E2 (pmol day⁻¹). The total phytoestrogen estrogenic effect is measured in pM of E2, with a mean of 28.28 (SD = 23.97) and median of 21.50. The mean consumption of phytoestrogens in Mexican university students is similar to the consumption found in similar studies in the United States, England, Germany, and Spain (<1 mg day⁻¹). Phytoestrogens can be beneficial in adult women during perimenopause and menopause due to their estrogenic effects, but they are less recommended for women in the fertile stage, as, for example, in the study presented here, because they could function as endocrine disruptors. They are not recommended as dietary supplements for young women or pregnant women.
... The number and types of EDCs are increasing year by year, and some of these stable substances persist in the environment without degradation [128]. EDCs include smoke-derived compounds, polybrominated diphenyl ether, "non-persistent" phenolic compounds, heavy metals, and persistent organic pollutants [127]; flame retardants, detergents, plastics, industrial and household products, and pesticides/herbicides [129]; phthalates, perfluoroalkyl substances [130]; ethylbenzene, m/p-xylene, o-xylene, toluene, cyclohexanone, 2-butoxyethanol, butylated hydroxytoluene, cyclohexanone, styrene, and hexane [131]; monomers of plastic materials, polycarbonates, epoxy resins [132]; triclosan [127,130] and Bisphenol A (BPA) [130,132]. Epidemiological and experimental studies have shown that the fetal or neonatal period in utero is a particularly sensitive time for exposure. ...
... The number and types of EDCs are increasing year by year, and some of these stable substances persist in the environment without degradation [128]. EDCs include smoke-derived compounds, polybrominated diphenyl ether, "non-persistent" phenolic compounds, heavy metals, and persistent organic pollutants [127]; flame retardants, detergents, plastics, industrial and household products, and pesticides/herbicides [129]; phthalates, perfluoroalkyl substances [130]; ethylbenzene, m/p-xylene, o-xylene, toluene, cyclohexanone, 2-butoxyethanol, butylated hydroxytoluene, cyclohexanone, styrene, and hexane [131]; monomers of plastic materials, polycarbonates, epoxy resins [132]; triclosan [127,130] and Bisphenol A (BPA) [130,132]. Epidemiological and experimental studies have shown that the fetal or neonatal period in utero is a particularly sensitive time for exposure. The lipophilic structure allows the EDCs to increase their own retention capacity during fat deposition. ...
... Furthermore, even low levels of EDCs increase the risk of obesity. Heras-González et al. [132] estimated dietary exposure to phytoestrogens and BPA and their potential obesogenic effects in a group of Spanish schoolchildren. The diet of this group had an average total estrogenic volume of 5.10-12 M eq.E2 (5 pmol/day). ...
Nowadays, obesity is one of the largest public health problems worldwide. In the last few decades, there has been a marked increase in the obesity epidemic and its related comorbidities. Worldwide, more than 2.2 billion people (33%) are affected by overweight or obesity (712 million, 10%) and its associated metabolic complications. Although a high heritability of obesity has been estimated, the genetic variants conducted from genetic association studies only partially explain the variation of body mass index. This has led to a growing interest in understanding the potential role of epigenetics as a key regulator of gene-environment interactions on the development of obesity and its associated complications. Rapid advances in epigenetic research methods and reduced costs of epigenome-wide association studies have led to a great expansion of population-based studies. The field of epigenetics and metabolic diseases such as obesity has advanced rapidly in a short period of time. The main epigenetic mechanisms include DNA methylation, histone modifications, microRNA (miRNA)-mediated regulation and so on. DNA methylation is the most investigated epigenetic mechanism. Preliminary evidence from animal and human studies supports the effect of epigenetics on obesity. Studies of epigenome-wide association studies and genome-wide histone modifications from different biological specimens such as blood samples (newborn, children, adolescent, youth, woman, man, twin, race, and meta-analysis), adipose tissues, skeletal muscle cells, placenta, and saliva have reported the differential expression status of multiple genes before and after obesity interventions and have identified multiple candidate genes and biological markers. These findings may improve the understanding of the complex etiology of obesity and its related comorbidities, and help to predict an individual’s risk of obesity at a young age and open possibilities for introducing targeted prevention and treatment strategies.
... Side effects of N-EDCs were also found in the cardiovascular system (four papers), in the bone system (four papers) and in adipose tissue (seven papers) ( Table 7). Adipose tissue 7 [10,28,29,34,42,48,49] N-EDCs can induce adverse effects during specific susceptibility windows such as pregnancy and childhood. As shown in Table 8, 9 papers addressed toxicological effects during pregnancy and 21 during childhood, including the perinatal and pubertal periods. ...
... Indeed, depending on the age group concerned, PEs can also be considered to promote obesity. Research conducted on children of 7 to 10 years of age suggested that isoflavone intake leads to a tendency towards obesity [48]. Additionally, maternal soy consumption during pregnancy has been associated with a higher birth weight in female neonates [49]. ...
Endocrine-disrupting compounds are chemicals that alter the normal functioning of the endocrine system of living organisms. They can be natural (N-EDCs) or synthetic compounds (S-EDCs). N-EDCs can belong to different groups, such as phytoestrogens (PEs), including flavonoids, or mycotoxins originating from plants or fungi, and cyanotoxins, derived from bacteria. Humans encounter these substances in their daily lives. The aim of this rapid review (RR) is to provide a fine mapping of N-EDCs and their toxicological effects on human health in terms of various medical conditions or adverse consequences. This work is based on an extensive literature search and follows a rigorous step-by-step approach (search strategy, analysis strategy and data extraction), to select eligible papers published between 2019 and 2023 in the PubMed database, and to define a set of aspects characterizing N-EDCs and the different human target systems. Of the N-EDCs identified in this RR, flavonoids are the most representative class. Male and female reproductive systems were the targets most affected by N-EDCs, followed by the endocrine, nervous, bone and cardiovascular systems. In addition, the perinatal, pubertal and pregnancy periods were found to be particularly susceptible to natural endocrine disruptors. Considering their current daily use, more toxicological research on N-EDCs is required.
... EDs such as bisphenol A (BPA), BPA glycidyl methacrylate (bis-GMA), and other BPA acrylate-based derivatives have been related to endocrine disorders, including estrogen-like effect, type 2 diabetes, metabolic syndrome, and obesity, among other metabolic disorders (6)(7)(8)(9)(10)(11). Estrogenic properties of BPA were reported in 1936 (12). Human exposure to BPA is universal, and unconjugated BPA molecules have been found in human biological samples (blood, tissues, urine, saliva, and milk) (9,(13)(14)(15). ...
... A factor considered to partially explain the obesity situation of schoolchildren in southern Spain has been the average intake of sugar (49); in addition, factors such as EI and PA have been considered. Exposure to ED, considered estrogenic and obesogenic, allowed estimating risks of obesity in schoolchildren between 7 and 10 years old, estimating the relationship between obesity and exposure to phytoestrogens and BPA through diet (15). ...
Introduction
Endocrine disruptors such as bisphenol A (BPA), BPA glycidyl methacrylate, and other BPA acrylate–based derivatives have been related to type 2 diabetes, the metabolic syndrome, and obesity, among other metabolic disorders. The objective of this study is to examine the influence of BPA exposure by saliva analysis and daily physical activity on the risk of overweight/obesity in schoolchildren from southern Spain.
Methods
The study included 300 children (53.5% girls) aged 7–10 years. Participants completed a questionnaire with four sections: participant data, including demographic information and life and family habits; semi-quantitative food frequency questionnaire; anthropometric variables; and physical activity variables. All participants underwent dental examination, when the presence of sealants/composites in each tooth and other dental alterations was recorded, and samples of whole saliva were collected for UHPLC-MS/MS analyses.
Results
Risk of overweight/obesity was significantly influenced by body fat composition (OR = 10.77), not walking to and from school (OR = 1.38), lesser energy expenditure in sedentary activities (OR = 12.71), greater energy expenditure in sports (OR =1.62), and exposure to BPA from dental sealants/composites (OR = 1.38; p = 0.058).
Discussion
Further research is warranted on this issue in children, who may be especially vulnerable to the negative health effects of endocrine disruption.
... Bisphenol A (BPA) is considered one of the most widespread endocrine-disrupting chemicals (EDCs), substances affecting human health and impacting not only the endocrine system but also immune and metabolic functions [1,2]. Many lines of evidence have highlighted the link between impaired immunity and obesity and their relationship with EDC exposure [3,4]. ...
... Previous evidence describes BPA, similarly to other EDCs, as an inducer of epigenetic transgenerational inheritance of obesity [1]. Embryonic, perinatal, and early life exposure to BPA generates metabolic alterations later in life predisposing to obesity and diabetes [1,2], evidencing its role in the etiology of metabolic disorders. Here, we have determined the mechanisms underlined to liver toxic effect of BPA in adult obese mice, regardless of perinatal exposure, since obesity-related disorders are associated with BPA exposure in both children and adults [32,33]. ...
Lines of evidence have shown the embryogenic and transgenerational impact of bisphenol A (BPA), an endocrine-disrupting chemical, on immune-metabolic alterations, inflammation, and oxidative stress, while BPA toxic effects in adult obese mice are still overlooked. Here, we evaluate BPA’s worsening effect on several hepatic maladaptive processes associated to high-fat diet (HFD)-induced obesity in mice. After 12 weeks HFD feeding, C57Bl/6J male mice were exposed daily to BPA (50 μg/kg per os) along with HFD for 3 weeks. Glucose tolerance and lipid metabolism were examined in serum and/or liver. Hepatic oxidative damage (reactive oxygen species, malondialdehyde, antioxidant enzymes), and mitochondrial respiratory capacity were evaluated. Moreover, liver damage progression and inflammatory/immune response were determined by histological and molecular analysis. BPA amplified HFD-induced alteration of key factors involved in glucose and lipid metabolism, liver triglycerides accumulation, and worsened mitochondrial dysfunction by increasing oxidative stress and reducing antioxidant defense. The exacerbation by BPA of hepatic immune-metabolic dysfunction induced by HFD was shown by increased toll-like receptor-4 and its downstream pathways (i.e., NF-kB and NLRP3 inflammasome) amplifying inflammatory cytokine transcription and promoting fibrosis progression. This study evidences that BPA exposure represents an additional risk factor for the progression of fatty liver diseases strictly related to the cross-talk between oxidative stress and immune-metabolic impairment due to obesity.
... The topic has gained signicant public attention in recent years due to these chemicals' adverse health effects, 16 especially signicant negative impacts on reproductive abilities as endocrine disruptors even at low concentrations. 3,12,[17][18][19][20] It has been suggested that BPA may affect human reproductive and other systems by acting like human hormones. 21 In response, BPS has been one of the most widely used BPA replacements introduced by manufacturers to make "BPA-free" products. ...
Thermal papers are a significant source of exposure to bisphenol A (BPA) and other phenolic compounds (PCs), absorbed through the skin via dermal contact. This study analyzed thermal paper receipts from various commercial settings in Türkiye to assess BPA and its structural analogs. For both deterministic and probabilistic risk assessments, the estimated daily intake (EDI), hazard quotient (HQ), and hazard index (HI) were calculated for the general population and workers exposed via dermal contact from handling thermal receipts. The results showed that BPA and bisphenol S (BPS) were the most frequently detected chemicals (detected in 99% and 100% of samples, respectively) with concentrations ranging from 1.98–1061 μg per g paper and 0.070–210 μg per g paper in thermal paper receipts in Türkiye, respectively. The EDI of PCs based on the mean concentration determined in the samples for the general population ranged between 0.00000184 μg per kg per day and 0.000445 μg per kg per day, whereas it ranged between 0.0000919 μg per kg per day and 0.022 μg per kg per day for occupational exposure of workers. The EDI value based on the mean concentration detected in samples was 0.000445 μg per kg per day and 0.00223 μg per kg per day for the general population and occupational exposure, respectively. Exposure to BPS was lower, resulting in exposure values of 0.000039 μg per kg per day and 0.002 μg per kg per day for the general population and occupational exposure, respectively. Although these mean concentration based exposure levels are below the U.S. EPA reference dose (50 μg per kg per day for BPA), they exceed the more stringent European Food Safety Authority (EFSA) total daily intake (TDI) limits set for BPA (0.0002 μg per kg per day) in some cases, indicating potential health risks. The HQ and HI analyses further underscore the risks, particularly for workers, with HI values surpassing safe thresholds. The study calls for stricter regulations on BPA and its analogs in thermal papers due to the significant risks, even from BPA-free products that use BPS as a substitute.
... In modern society, high-fat diet consumption is thought to be a main contributing factor for the increased incidence of metabolic syndrome, including obesity and IR [40]. Diet is considered the main source of BPA exposure [41]; thus, the consumption of fat-rich products favors coexposure to BPA [42]. The amplifying effect of BPA on HFD-induced IR emphasizes the importance of studying interactions between EDCs and obesity. ...
Objective:
Exposure to bisphenol A (BPA) has been shown to increase the prevalence of obesity and its related insulin resistance (IR). Ceramide is a sphingolipid known to facilitate the production of proinflammatory cytokines and subsequently exacerbate inflammation and IR during the progression of obesity. Here, we investigated the effects of BPA exposure on ceramide de novo synthesis and whether increased ceramides aggravate adipose tissue (AT) inflammation and obesity-related IR.
Methods:
A population-based case-control study was conducted to explore the relationship between BPA exposure and IR and the potential role of ceramide in AT in obesity. Next, we used mice reared on a normal chow diet (NCD) or a high-fat diet (HFD) to verify the results from the population study and then investigated the role of ceramides in low-level BPA exposure with HFD-induced IR and AT inflammation in mice treated with or without myriocin (an inhibitor of the rate-limiting enzyme in de novo ceramide synthesis).
Results:
BPA levels are higher in obese individuals and are significantly associated with AT inflammation and IR. Specific subtypes of ceramides mediated the associations between BPA and obesity, obesity-related IR and AT inflammation in the obesity group. In animal experiments, BPA exposure facilitated ceramide accumulation in AT, activated PKCζ, promoted AT inflammation, increased the expression and secretion of proinflammatory cytokines via the JNK/NF-κB pathway, and lowered insulin sensitivity by disrupting IRS1-PI3K-AKT signaling in mice fed a HFD. Myriocin suppressed BPA-induced AT inflammation and IR.
Conclusion:
These findings indicate that BPA aggravates obesity-induced IR, which is partly via increased de novo synthesis of ceramides and subsequent promotion of AT inflammation. Ceramide synthesis could be a potential target for the prevention of environmental BPA exposure-related metabolic diseases.
... In light of this, we hypothesized that colostrum could be a media helping to identify determinants of exposure to ClxBPA and BPA during pregnancy. While numerous studies have studied the determinants of BPA exposure, none has the colostrum as matrix, none has studied water exposure as predictors and none has assessed the determinants of ClxBPA presence (Braun et al. 2011;Callan et al. 2013;Casas et al. 2013;Philips et al. 2018b;Quirós-Alcalá et al. 2013;Pacyga et al. 2019;Zhao et al. 2019;Salamanca-Fernández et al. 2020;González et al. 2020;Heras-González et al. 2020;Kim et al. 2020). We made the hypothesis that we will find the same sociodemographic or consumption determinants and particularly water consumption habits. ...
Chlorinated derivatives of bisphenol A (ClxBPA) are endocrine disruptors that have seldom been studied. The aim was to assess the determinants of ClxBPA presence and bisphenol A (BPA) concentration in colostrum fluid. Pregnant women participating in the EDDS cohort study (France, 2011–2014) received two visits at home during their pregnancies, the objectives being to inform ourselves on their sociodemographic characteristics and consumption habits and to collect their urine samples. A colostrum sample was collected at delivery. All samples were analyzed using solid-phase extraction coupled with ultra-high-performance liquid chromatography isotope dilution tandem mass spectrometry method. Among 100 pregnant women, 32% had at least one ClxBPA detected in their colostrum fluid, 19% monochlorobisphenol-A, 23% dichlorobisphenol-A, 16% trichlorobisphenol-A and 2% tetrachlorobisphenol-A. After adjustment for sociodemographic factors, sample collection between 24 and 48 h after delivery was associated with lower ClxBPA presence in colostrum (OR = 0.06, 95%CI (0.01, 0.66) compared to colostrum collected during the first 24 h. BPA was detected in 60 colostrum fluids (61%) with mean concentrations of 2.1 ± 6.9 ng/mL. After adjustment, BPA was higher among women currently smoking during the third trimester (β = 1.20 95%CI (0.30, 2.09)) and lower when the sample was collected between 24 and 48 h after delivery (β = -0.72 95%CI (-1.43, -0.02)) compared to colostrum collection during the first 24 h after delivery. Sociodemographic factors, water exposure and food consumption were not associated with presence of ClxBPA in colostrum and concentration of BPA. Confirmation of these results with further powerful studies are needed, particularly those on kinetic investigation of ClxBPA excretion in colostrum would be interesting to improve storage condition’s knowledge.
... He is also involved in the studies of tyrosine kinase inhibitors for the treatment of breast and colon cancer, in the Saudi population. alcohol consumption, high cholesterol, diabetics, coronary diseases, hereditary factors, severe smoking, high blood pressure, fatigue, and depression [7]. The prevalence of strokes is based on sex, with men being more susceptible. ...
Cerebral infarction (stroke) is a fatal disease owing to blockage of the brain blood vessels. Although it is often considered a disease of old age, unhealthy diets, stressful lifestyles, and declining environmental conditions have significantly increased the number of cases of stroke in younger populations. Therefore, immediate and long-term injury control, restoration of brain functions, accurate and early evaluation of stroke risk and effective drug therapy are required. Physiological limitations hindered the effective management of cerebral stroke. The emergence of nanomedicine overcomes the issues associated with conventional treatment and physiological barriers. In addition, development of nanotheranostics for stroke management as diagnostic, imaging and therapeutics in one platform has been discussed. Furthermore, clinical progress of drugs to nanocarriers also discussed.
... BPA is able to bind to multiple human and animal receptors includіng estrogen (ERs), androgen (ARs), and thyroid hormone receptors (TRs) as well as to nuclear transcription factors like the peroxіsome proliferator-activated receptor (PPAR) and the aryl hydrocarbon receptor (AhR) (Michalowicz 2014). The estrogenic activity of BPA and its analogues has been extensively investigated and it was fіrst reported for BPA by Dodds et al., іn 1936(Heras-Gonzalez et al., 2020. Gaido et al. (1997) found that the estrogenicity of BPA in vitro was significantly weaker than 17β-estradiol (E2). ...
Bisphenol A (BPA) is one of the most common endocrine disruptors found in the environment and its harmful health effects in humans and wildlife have been extensively reported One of the main aims of this review was to examine the metabolic pathways of BPA and BPA substitutes and the endocrine disrupting properties of their metabolites. According to the available literature, phase I and phase II metabolic reactions play an important role in the detoxification process of bisphenols (BPs), but their metabolism can also lead to the formation of highly reactive metabolites. The second part of this work addresses the associations between exposure to BPA and its analogues with the alterations in miRNAs expression and the effects of single nucleotide polymorphisms (SNPs). Available scientific evidence shows that BPs can dysregulate the expression of several miRNAs, and in turn, these miRNAs could be considered as epigenetic biomarkers to prevent the development of a variety of BP-mediated diseases. Interestingly, genetic polymorphisms are able to modify the relationship of BPA exposure with the risk of adverse health effects, suggesting that interindividual genetic differences modulate the susceptibility to the effects of environmental contaminants.
... As reported by Heras-Gonzales et al., there is a strong correlation between obesity, lifestyle and diet and exposure to ED chemicals. Several studies reported that the migration of BPA from drink and food packaging, plastic baby bottles, and the coating of cans is associated with obesity, classifying them as obesogens (61). Diet also strongly influences urinary BPA levels and changes in diet are attributable to alterations in urinary BPA levels: the results of the present study suggest that a plastic-free lifestyle may be related to a reduction in urinary BPA levels. ...
Bisphenol A (BPA) is an endocrine disruptor (ED) frequently used in food packaging. BPA is used as a monomer in the manufacture of some food packaging. This study aimed to evaluate the urinary BPA concentration in an Italian pediatric cohort, testing the levels of this ED over a period of 6 months, evaluating the effects of a diet regimen with a reduction of Plastic Food Packaging (PFP). One hundred thirty Italian children were enrolled and divided into two groups “School Canteen” and “No School Canteen.” The first group consumed one meal at school using a plastic-free service for 5 days/weeks, while the other group did not modify their normal meal-time habits. The BPA levels were tested in urine samples at three time points: T0, is the time before the application of the plastic-free regimen diet; T3, 3 months later; and T6, 6 months later. A reduction of urine BPA levels was detected in the “School Canteen” group. In particular, the reduction was significant analyzing both the intra (among the three testing times) group and inter (between “School Canteen” and “No School Canteen”) group variability. Our results show the effects of a diet regimen with a reduction of PFP, demonstrating a connection between urinary BPA levels and food packaging.
Dietary risk factors play a fundamental role in the prevention and progression of atherosclerosis and PAD (Peripheral Arterial Disease). The impact of nutrition, however, defined as the process of taking in food and using it for growth, metabolism and repair, remains undefined with regard to PAD. This article describes the interplay between nutrition and the development/progression of PAD. We reviewed 688 articles, including key articles, narrative and systematic reviews, meta-analyses and clinical studies. We analyzed the interaction between nutrition and PAD predictors, and subsequently created four descriptive tables to summarize the relationship between PAD, dietary risk factors and outcomes. We comprehensively reviewed the role of well-studied diets (Mediterranean, vegetarian/vegan, low-carbohydrate ketogenic and intermittent fasting diet) and prevalent eating behaviors (emotional and binge eating, night eating and sleeping disorders, anorexia, bulimia, skipping meals, home cooking and fast/ultra-processed food consumption) on the traditional risk factors of PAD. Moreover, we analyzed the interplay between PAD and nutritional status, nutrients, dietary patterns and eating habits. Dietary patterns and eating disorders affect the development and progression of PAD, as well as its disabling complications including major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nutrition and dietary risk factor modification are important targets to reduce the risk of PAD as well as the subsequent development of MACE and MALE.
Owing to its intricate pathophysiology, cerebral stroke is a serious medical condition caused by interruption or obstruction of blood supply (blockage of vasculature) to the brain tissues which results in diminished supply of essential nutrients and oxygen (hypoxia) and ultimate necrosis of neuronal tissues. A prompt risks assessment and immediate rational therapeutic plan with proficient neuroprotection play critically important role in the effective management of this neuronal emergency. Various conventional medications are being used for treatment of acute ischemic cerebral stroke but fibrinolytic agents, alone or in combination with other agents are considered the mainstay. These clot-busting agents effectively restore blood supply (reperfusion) to ischemic regions of the brain; however, their clinical significance is hampered due to various factors such as short plasma half-life, limited distribution to brain tissues due to the presence of highly efficient physiological barrier, blood brain barrier (BBB), and lacking of target-specific delivery to the ischemic brain regions. To alleviate these issues, various types of nanomedicines such as polymeric nanoparticles (NPs), liposomes, nanoemulsion, micelles and dendrimers have been designed and evaluated. The implication of these newer therapies (nanomedicines) have revolutionized the therapeutic outcomes by improving the plasma half-life, permeation across BBB, efficient distribution to ischemic cerebral tissues and neuroprotection. Furthermore, the adaptation of some diverse techniques including PEGylation, tethering of targeting ligands on the surfaces of nanomedicines, and pH responsive features have also been pondered. The implication of these emerging adaptations have shown remarkable potential in maximizing the targeting efficiency of drugs to ischemic brain tissues, simultaneous delivery of drugs and imaging agents (for early prognosis as well as monitoring of therapy), and therapeutic outcomes such as long-term neuroprotection.
Common plasticizers and their alternatives are environmentally ubiquitous and have become a global problem. In this study, common plasticizers (phthalates and metabolites) and new alternatives [bisphenol analogs, t-butylphenyl diphenyl phosphate (BPDP), and bisphenol A bis(diphenyl phosphate) (BDP)] were quantified in urine and hair samples from children in Hong Kong, drinking water (tap water/bottled water) samples, and airborne particle samples from 17 kindergartens in Hong Kong. The results suggested that locally, children were exposed to various plasticizers and their alternatives. High concentrations of BPDP and BDP were present in urine, hair, tap water, bottled water, and air particulate samples. The geometric mean (GM) concentrations of phthalate metabolites in urine samples (126–2140 ng/L, detection frequencies < 81%) were lower than those detected in Japanese and German children in previous studies. However, a comparison of the estimated daily intake values for phthalates in tap water [median: 10.7–115 ng/kg body weight bw/day] and air particles (median: 1.23–7.39 ng/kg bw/day) with the corresponding reference doses indicated no risk. Bisphenol analogs were detected in 15–64% of urine samples at GM concentrations of 5.26–98.1 ng/L, in 7–74% of hair samples at GM concentrations of 57.5–2390 pg/g, in 59–100% of kindergarten air samples at GM concentrations of 43.1–222 pg/m³, and in 33–100% of tap water samples at GM concentrations of 0.90–3.70 ng/L. A significant correlation was detected between the concentrations of bisphenol F in hair and urine samples (r = .489, p < .05). The estimated daily urinary excretion values of bisphenol analogs suggest that exposure among children via tap water intake and airborne particle inhalation in kindergartens cannot be ignored in Hong Kong.
The microflora of the digestive tract is composed of a unique set of bacteria, yeasts, viruses and other microorganisms, generally known as the microbiome. The microbiome exhibits considerable inter-individual variability, with up to two-thirds of the microflora differing between individuals. Because of this, the variable intestinal microflora is responsible for many differences in metabolic, hormonal and immunological processes in humans and animals. Significant differences have been observed in the metabolism of phytoestrogens, naturally occurring substances that possess estrogenic or anti-estrogenic activity. These substances occur predominately in legumes, especially in soy and many soy products. Because of their effects, phytoestrogens are used as an alternative therapy for menopausal disorders and benign prostate hyperplasia. In connection with the worldwide expansion of soy products as part of healthy lifestyles including vegetarianism and veganism, phytoestrogens have become a regular part of everyday life. The activity of phytoestrogens is strongly dependent on the microbiome. Their metabolites have stronger estrogenic activity than the natural substances themselves, and because of the variability in microbiomes, there are large differences in the effects of phytoestrogens among individuals.
Background:
Phytoestrogens, naturally occurring plant chemicals, have long been thought to confer beneficial effects on human cardiovascular and metabolic health. However, recent epidemiological studies, have yielded conflicting outcomes, in which phytoestrogen consumption was both positively and negatively correlated with adiposity. Interestingly, several dietary phytoestrogens are known to stimulate or inhibit the activity of the peroxisome proliferator-activated receptor gamma (PPARγ), a key physiological regulator of adipogenesis.
Objective:
The objective of this study was to test the hypothesis that the pro- or anti-adipogenic activity of phytoestrogen chemicals is related to the ability to activate PPARγ in adipocytes.
Methods:
The effects of resveratrol and the soy isoflavones genistein and daidzein on adipogenesis were examined in cell-based assays using the 3T3-L1 cell model. In parallel, ligand-mediated alterations in PPARγ target gene expression were measured by quantitative polymerase chain reaction. The agonist/antagonist activities of phytoestrogens on PPARγ were further assessed by quantifying their ability to affect recruitment of transcriptional cofactors to the receptor.
Results:
Resveratrol displayed significant anti-adipogenic activities as exhibited by the ability to antagonize PPARγ-dependent adipocyte differentiation, down-regulate genes involved in lipid metabolism, block cofactor recruitment to PPARγ, and antagonize the effects of the PPARγ agonist rosiglitazone. In contrast, genistein and daidzein functioned as PPARγ agonists while also displaying pro-adipogenic activities.
Conclusions:
These data provide biological evidence that the pro- or anti-obesity effects of phytoestrogens are related to their relative agonist/antagonist activity on PPARγ. Thus, PPARγ-activation assays may enable the screening of dietary components and identification of agents with adipogenic activities. https://doi.org/10.1289/EHP3444.
Phytoestrogens are naturally occurring nonsteroidal phenolic plant compounds that, due to their molecular structure and size, resemble vertebrate steroids estrogens. This review is focused on plant flavonoids isoflavones, which are ranked among the most estrogenic compounds. The main dietary sources of isoflavones for humans are soybean and soybean products, which contain mainly daidzein and genistein. When they are consumed, they exert estrogenic and/or antiestrogenic effects. Isoflavones are considered chemoprotective and can be used as an alternative therapy for a wide range of hormonal disorders, including several cancer types, namely breast cancer and prostate cancer, cardiovascular diseases, osteoporosis, or menopausal symptoms. On the other hand, isoflavones may also be considered endocrine disruptors with possible negative influences on the state of health in a certain part of the population or on the environment. This review deals with isoflavone classification, structure, and occurrence, with their metabolism, biological, and health effects in humans and animals, and with their utilization and potential risks.
Dietary guidelines universally advise adherence to plant-based diets. Plant-based foods confer considerable health benefits, partly attributable to their abundant micronutrient (e.g., polyphenol) content. Interest in polyphenols is largely focused on the contribution of their antioxidant activity to the prevention of various disorders, including cardiovascular disease and cancer. Polyphenols are classified into groups, such as stilbenes, flavonoids, phenolic acids, lignans and others. Lignans, which possess a steroid-like chemical structure and are defined as phytoestrogens, are of particular interest to researchers. Traditionally, health benefits attributed to lignans have included a lowered risk of heart disease, menopausal symptoms, osteoporosis and breast cancer. However, the intake of naturally lignan-rich foods varies with the type of diet. Consequently, based on the latest humans’ findings and gathered information on lignan-rich foods collected from Phenol Explorer database this review focuses on the potential health benefits attributable to the consumption of different diets containing naturally lignan-rich foods. Current evidence highlight the bioactive properties of lignans as human health-promoting molecules. Thus, dietary intake of lignan-rich foods could be a useful way to bolster the prevention of chronic illness, such as certain types of cancers and cardiovascular disease.
Phytoestrogens have structures that are very similar to endogen estradiol derived from plants. Phytoestrogens sources are widespread in Asian regions including in Indonesia. Its have health benefits including reproductive health, heart health, a role in weight loss, hormone-dependent tumours, bone and skin health, and the immune system. This review aimed to provide information on phytoestrogens’ effect on human health.
Since the inception of the term endocrine disruptor, the idea that the environment is an important determinant of phenotype has motivated researchers to explore the effect of low dose exposure to BPA during organogenesis. The syndrome observed was complex, affecting various endpoints such as reproduction and reproductive tissues, behavior, mammary gland development and carcinogenesis, glucose homeostasis, and obesity. This constellation of impacted endpoints suggests the possibility of complex interactions among the multiple effects of early BPA exposure. One key finding of our rodent studies was alterations of energy and amino-acid metabolism that were detected soon after birth and continued to be present at all time points examined through 6 months of age. The classical manifestations of obesity and associated elements of metabolic disease took a longer time to become apparent. Here we examine the validity of the often-mentioned lack of reproducibility of obesogenic effects of BPA, starting from the known environmental causes of variation, which are diverse and range from the theoretical like the individuation process and the non-monotonicity of the dose-response curve, to the very pragmatic like housing, feed, and time and route of exposure. We then explore environmental conditions that may hinder reproducibility and discuss the effect of confounding factors such as BPA-induced hyperactivity. In spite of all the potential sources of variation, we find that some obesogenic or metabolic effects of BPA are reproducibly observed when study conditions are analogous. We recommend that study authors describe details of their study conditions including the environment, husbandry, and feed. Finally, we show that when experimental conditions are strictly maintained, reproducibility, and stability of the obese phenotype is consistently observed.
Although Scientific Societies have stated that there are very few indications for the use of soy-based formula (SF) in infant nutrition, their utilization rates have been repeatedly found to be higher than expected. It is likely that a significant role in this regard is played by the belief that the use of SF during infancy can reduce the risk of the development of several diseases later in life. Although no definitive data that can substantiate these claims have been collected, many people perceive soy consumption to confer significant health benefits and might also use soy for infant nutrition. However, not all the problems regarding safety of SF in infants have been definitively solved. Among risks, the potentially toxic role of the phyto-oestrogens contained in SF is not definitively established. In vitro and animal studies have raised suspicions that SF could have potentially negative effects on sexual development and reproductive function, neurobehavioral development, immune function, and thyroid function. Several studies in humans have aimed to assess whether the results of animal studies can be applied to humans and whether SF can be used in infants following the official recommendations. The results are somewhat conflicting. The aim of this narrative review is to discuss what is presently known regarding the impact of phyto-oestrogens in SF on early and late child development. PubMed was used to search for the studies published from January 1980 to June 2017 using the keywords: “soy,” “soy formula,” “child,” “phytoestrogens.” Analysis of the literature showed that a global evaluation of the impact of modern SFs on human development seems to suggest that their use is not associated with relevant abnormalities. Only children with congenital hypothyroidism need adequate monitoring of thyroid function.
Phytoestrogens are plant‐derived dietary compounds with structural similarity to 17‐β‐oestradiol (E2), the primary female sex hormone. This structural similarity to E2 enables phytoestrogens to cause (anti)oestrogenic effects by binding to the oestrogen receptors. The aim of the present review is to present a state‐of‐the‐art overview of the potential health effects of dietary phytoestrogens. Various beneficial health effects have been ascribed to phytoestrogens, such as a lowered risk of menopausal symptoms like hot flushes and osteoporosis, lowered risks of cardiovascular disease, obesity, metabolic syndrome and type 2 diabetes, brain function disorders, breast cancer, prostate cancer, bowel cancer and other cancers. In contrast to these beneficial health claims, the (anti)oestrogenic properties of phytoestrogens have also raised concerns since they might act as endocrine disruptors, indicating a potential to cause adverse health effects. The literature overview presented in this paper illustrates that several potential health benefits of phytoestrogens have been reported but that, given the data on potential adverse health effects, the current evidence on these beneficial health effects is not so obvious that they clearly outweigh the possible health risks. Furthermore, the data currently available are not sufficient to support a more refined (semi) quantitative risk–benefit analysis. This implies that a definite conclusion on possible beneficial health effects of phytoestrogens cannot be made.
Linked Articles
This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc
An 'in culture' bioassay was developed to assess the estrogenicity of xenobiotics using human breast estrogen-sensitive MCF7 cells. The assay compares the cell yield achieved after 6 days of culture in medium supplemented with 10% charcoal-dextran stripped human serum in the presence or absence of estradiol (10 -13 to 10 -9 M), and with diverse concentrations of xenobiotics suspected of being estrogenic. Among the chemicals tested (pesticides, phytoestrogens, polychlorobiphenyls, alkylphenols and phytohormones), the bioassay confirmed the estrogenicity of compounds previously shown to be estrogenic in rodent models; no false positives were found. In addition, a case of estrogen contamination due to the shedding of estrogenic xenobiotics by polystyrene labware was solved using this assay. This bioassay has the following advantages over those currently used: a) it is easy to perform: it requires a standard cell culture facility and a human estrogen-sensitive cell line; b) it is relevant to humans, since it relies on the responses of a human cell line growing in human serum-supplemented media, and c) it is sensitive since it detects 10pg/ml estradiol-17β. This assay may also be used to determine the presence of estrogenic xenobiotics in soil, water, human foods and animal feeds. Among the foods and feeds tested, a soy bean drink and a laboratory rat chow were shown to be estrogenic. We believe that the adoption of this bioassay by industry and regulatory agencies may provide a rigorous tool to identify estrogenic xenobiotics.
In the last decades, many reports have focused the attention on deleterious effects of novel environmental chemical compounds, including bisphenol A (BPA), on human health. BPA, a common and widely chemical contaminant acting as endocrine disruptor, accumulates in adipose tissue and may affect adipocyte metabolic and inflammatory functions. BPA, at low chronic doses, is now considered as an obesogen compound, and might contribute to the rise of metabolic syndrome, visceral adiposity and diabetes epidemics. The BPA worldwide presence in the environment is responsible for chronic exposure during vulnerable periods, such as foetal and neonatal life. The BPA source of contamination can occur via food, beverage, wastewater, air, dust and soil. BPA, as lipophilic compound, may accumulate into the adipose tissue already during foetal life and may affect adulthood health, through adverse effects on the growth and development of organs and tissues. Thus, based on several studies, it would be crucial to consider further actions aimed to refine risk assessment at least in vulnerable population, such as foetuses, infants and young children, to prevent metabolic diseases and obesity.
Phenols and parabens show some evidence for endocrine disruption in laboratory animals. The goal of the Methods Advancement for Milk Analysis (MAMA) Study was to develop or adapt methods to measure parabens (methyl, ethyl, butyl, propyl) and phenols (bisphenol A (BPA), 2,4- and 2,5-dichlorophenol, benzophenone-3, triclosan) in urine, milk and serum twice during lactation, to compare concentrations across matrices and with endogenous biomarkers among 34 North Carolina women. These non-persistent chemicals were detected in most urine samples (53-100%) and less frequently in milk or serum; concentrations differed by matrix. Although urinary parabens, triclosan and dichlorophenols concentrations correlated significantly at two time points, those of BPA and benzophenone-3 did not, suggesting considerable variability in those exposures. These pilot data suggest that nursing mothers are exposed to phenols and parabens; urine is the best measurement matrix; and correlations between chemical and endogenous immune-related biomarkers merit further investigation.
Copyright © 2014. Published by Elsevier Inc.
Background: In Spain, there are some organizations and scientific societies that have edited reference values of recommended nutrient intake, but whose data does not always agree in terms of format and content. Aims: To review the definitions, data and methodology that other countries or groups of countries have followed to obtain and document their own reference values in order to offer basic information to facilitate the establishment of the best reference values for the Spanish population. Field: Review of the available information in different countries (or groups of countries) from the European Union, the United States and World Health Organization. The analysed data concerned to healthy populations. Conclusions: Reference intakes differ among the examined countries according to population groups, included nutrients, methodology and frequency of published reviews. However, most of the countries define major concepts in the same way, although with different names in each country. On the other hand, most of the studied cases represent only a scientific organization in charge of the publication and update of the values of dietary reference intakes, but not in Spain. In that context, it looks convenient to reach a consensus among all Spanish organizations and scientific societies that are involved in this task, in order to establish an acceptable reference values.
Bisphenol-A (BPA) is a potential endocrine disruptor impacting metabolic processes and increasing the risk of obesity. To determine whether urine BPA level is associated with overweight/obesity in school-age children, we examined 1,326 students in grades 4-12 from three schools (one elementary, one middle, and one high school) in Shanghai. More than 98% of eligible students participated. Total urine BPA concentration was measured and anthropometric measures were taken by trained research staff. Information on risk factors for childhood obesity was collected for potential confounders. Age- and gender-specific weight greater than 90(th) percentile of the underlying population was the outcome measure. After adjustment for potential confounders, a higher urine BPA level (≥2 µg/L), at the level corresponding to the median urine BPA level in the U.S. population, was associated with more than two-fold increased risk of having weight >90(th) percentile among girls aged 9-12 (adjusted odds ratio (aOR) = 2.32, 95% confidence interval: 1.15-4.65). The association showed a dose-response relationship with increasing urine BPA level associated with further increased risk of overweight (p = 0.006 for trend test). Other anthropometric measures of obesity showed similar results. The same association was not observed among boys. This gender difference of BPA effect was consistent with findings from experimental studies and previous epidemiological studies. Our study suggests that BPA could be a potential new environmental obesogen. Widespread exposure to BPA in the human population may also be contributing to the worldwide obesity epidemic.
Objective: To analyse the association between waist-to-height ratio (WtHR) and body fat and to develop predictive adiposity equations that will simplify the diagnosis of obesity in the paediatric age group.
Design: Cross-sectional study conducted in Spain during 2007 and 2008. Anthropometric dimensions were taken according to the International Biology Program. The children were classified as underweight, normal weight, overweight or obese according to national standards of percentage body fat (%BF). WtHR differences among nutritional status categories were evaluated using ANOVA. Correlation analysis and regression analysis were carried out using WtHR as a predictor variable for %BF. A t test was applied to the results obtained by the regression model and by the Siri equation. The degree of agreement between both methods was evaluated by estimating the intra-class correlation coefficient.
Setting: Elementary and secondary schools in Madrid (Spain).
Subjects: Girls (n 1158) and boys (n 1161) from 6 to 14 years old.
Results: WtHR differed significantly (P<0.001) depending on nutritional status category. This index was correlated (P<0.001) with all adiposity indicators. The mean %BF values estimated by the regression model (boys: %BF= 106.50 x WtHR – 28.36; girls: %BF= 89.73 x WtHR – 15.40) did not differ from those
obtained by the Siri equation. The intra-class correlation coefficient (0.85 in boys, 0.79 in girls) showed a high degree of concordance between both methods.
Conclusions: WtHR proved to be an effective method for predicting relative adiposity in 6–14-year-olds. The developed equations can help to simplify the diagnosis of obesity in schoolchildren.
Daidzein (1) is a natural estrogenic isoflavone. We report here that 1 can be transformed into anti-estrogenic ligands by simple alkyl substitutions of the 7-hydroxyl hydrogen. To test the effect of such structural modifications on the hormonal activities of the resulting compounds, a series of daidzein analogues have been designed and synthesized. When MCF-7 cells were treated with the analogues, those resulting from hydrogen substitution by isopropyl (3d), isobutyl (3f), cyclopentyl (3g), and pyrano- (2) inhibited cell proliferation, estrogen-induced transcriptional activity, and estrogen receptor (ER) regulated progesterone receptor (PgR) gene expression. However, methyl (3a) and ethyl (3b) substitutions of the hydroxyl proton only led to moderate reduction of the estrogenic activities. These results demonstrated the structural requirements for the transformation of daidzein from an ER agonist to an antagonist. The most effective analogue, 2, was found to reduce in vivo estrogen stimulated MCF-7 cell tumorigenesis using a xenograft mouse model.
Both bifidobacteria and clostridia are part of the natural gut microflora and while clostridia may be responsible for severe intestinal infections, bifidobacteria are probiotic microorganisms belonging to the most important prospective bacteria in the bowel. The antimicrobial activity of biochanin A was tested in vitro against six Bifidobacterium spp., and eight Clostridium spp. using the broth microdilution method. Biochanin A showed an inhibition against all clostridia in the range of minimum inhibitory concentrations (MIC) from 64 μg/mL (for Cl. clostridioforme, strains DSM 933 and I3) to 1,024 μg/mL (for Cl. perfringens, DSM 11778). No bifidobacteria were suppressed at four-fold higher concentration (MICs > 4,096) than MIC of Cl. perfringens. These results indicate selective growth inhibition of biochanin A and its potential use in antimicrobial prevention and/or protection.
Phytoestrogens are naturally occurring plantderived polyphenols with estrogenic potency. They are ubiquitous in diet and therefore, generally consumed. Among Europeans, the diet is rich in multiple putative phytoestrogens including flavonoids, tannins, stilbenoids, and lignans. These compounds have been suggested to provide beneficial effects on multiple menopause-related conditions as well as on development of hormone-dependent cancers, which has increased the interest in products and foods with high phytoestrogen content. However, phytoestrogens may as well have adverse estrogenicity related effects similar to any estrogen. Therefore, the assessment of estrogenic potency of dietary compounds is of critical importance. Due to the complex nature of estrogenicity, no single comprehensive test approach is available. Instead, several in vitro and in vivo assays are applied to evaluate estrogenic potency. In vitro estrogen receptor (ER) binding assays provide information on the ability of the compound to I) interact with ERs, II) bind to estrogen responsive element on promoter of the target gene as ligand-ER complex, and III) interact between the co-activator and ERs in ligand-dependent manner. In addition, transactivation assays in cells screen for ligand-induced ERmediated gene activation. Biochemical in vitro analysis can be used to test for possible effects on protein activities and E-screen assays to measure (anti)proliferative response in estrogen responsive cells. However, for assessment of estrogenicity in organs and tissues, in vivo approaches are essential. In females, the uterotrophic assay is applicable for testing ERa agonistic and antagonistic dietary compounds in immature or adult ovariectomized animals. In addition, mammary gland targeted estrogenicity can be detected as stimulated ductal elongation and altered formation of terminal end buds in immature or peripubertal animals. In males, Hershberger assay in peri-pubertal castrated rats can be used to detect (anti)androgenic/ (anti)estrogenic responses in accessory sex glands and other hormone regulated tissues. In addition to these short-term assays, sub-acute and chronic reproductive toxicity assays as well as two-generation studies can be applied for phytoestrogens to confirm their safety in long-term use. For reliable assessment of estrogenicity of dietary phytoestrogens in vivo, special emphasis should be focused on selection of the basal diet, route and doses of administration, and possible metabolic differences between the species used and humans. In conclusion, further development and standardization of the estrogenicity test methods are needed for better interpretation of both the potential benefits and risks of increasing consumption of phytoestrogens from diets and supplements.
We present data showing that some foods preserved in lacquer-coated cans and the liquid in them may acquire estrogenic activity. Hormonal activity was measured using the E-screen bioassay. The biological activity of vegetables packed in cans was a result of plastic monomers used in manufacturing the containers. The plastic monomer bisphenol-A, identified by mass spectrometry, was found as a contaminant not only in the liquid of the preserved vegetables but also in water autoclaved in the cans. The amount of bisphenol-A in the extracts accounted for all the hormonal activity measured. Although the presence of other xenoestrogens cannot be ruled out, it is apparent that all estrogenic activity in these cans was due to bisphenol-A leached from the lacquer coating. The use of plastic in food-packaging materials may require closer scrutiny to determine whether epoxy resins and polycarbonates contribute to human exposure to xenoestrogens.
The chemical structure of hydroxylated diphenylalkanes or bisphenols consists of two phenolic rings joined together through a bridging carbon. This class of endocrine disruptors that mimic estrogens is widely used in industry, particularly in plastics. Bisphenol F, bisphenol A, fluorine-containing bisphenol A (bisphenol AF), and other diphenylalkanes were found to be estrogenic in a bioassay with MCF7 human breast cancer cells in culture (E-SCREEN assay). Bisphenols promoted cell proliferation and increased the synthesis and secretion of cell type-specific proteins. When ranked by proliferative potency, the longer the alkyl substituent at the bridging carbon, the lower the concentration needed for maximal cell yield; the most active compound contained two propyl chains at the bridging carbon. Bisphenols with two hydroxyl groups in the para position and an angular configuration are suitable for appropriate hydrogen bonding to the acceptor site of the estrogen receptor. Our data suggest that estrogenicity is influenced not only by the length of the substituents at the bridging carbon but also by their nature. Because diphenylalkane derivatives are widespread and their production and use are increasing, potential exposure of humans to estrogenic bisphenols is becoming a significant issue. The hazardous effects of inadvertent exposure to bisphenol-releasing chemicals in professional workers and the general populations therefore deserve investigation.
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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.
We investigated the relative validity of an interview-administered FFQ to estimate phytoestrogen intake among South Asian women in the UK. A population-based sample of 108 healthy South Asian women completed random repeated monthly 24-h recalls [with a subsample (n = 58) also providing multiple plasma samples] over a period of 1 y followed by administration of the FFQ. The FFQ produced slightly higher estimates of phytoestrogen intake than the 24-h recalls, but the percentage of women classified into the same +/- 1 quartile by the 2 methods was high for all phytoestrogens (from 81 to 94%) with only a small percentage (<5%) being misclassified into extreme opposite quartiles. Energy-adjusted Spearman correlations coefficients between the estimates obtained by the FFQ and the 24-h recalls were 0.55 for genistein, 0.60 for daidzein, 0.70 for secoisolariciresinol, and 0.63 for matairesinol (all P < 0.001). Spearman correlation coefficients between the FFQ estimates and plasma levels were 0.21 (P = 0.12) for genistein, 0.32 (P = 0.02) for daidzein and 0.10 (P = 0.43) for enterolactone; the corresponding values for the 24-h recalls compared with plasma levels were 0.43 (P < 0.001), 0.40 (P = 0.002), and 0.08 (P = 0.50), respectively. The method of triads was used to estimate the validity coefficients (VCs) between the estimates provided by each assessment method and "true intake." The FFQ had the highest VC for lignans (0.91 vs. 0.73 for 24-h recalls and 0.11 for plasma samples) and satisfactory VCs for both genistein (0.46 vs. 0.95 and 0.45, respectively) and daidzein (0.67 vs. 0.83 and 0.45, respectively). This FFQ is thus a relatively valid tool with which to estimate phytoestrogen intake among South Asian women in the UK.
The indigenous intestinal microflora are involved in a variety of processes within the human body, and are important for maintaining host health. As such, interindividual differences in the ability to harbor certain intestinal bacteria might be associated with interindividual differences in health and/or disease susceptibility. In the last decade there has been considerable interest in phytoestrogen intakes in relation to human health. Daidzein, an isoflavone phytoestrogen found in soy, is metabolized to equol and O-desmethylangolensin (O-DMA) by intestinal bacteria. The specific bacterium/bacteria responsible for equol and O-DMA production in humans have yet to be identified definitively, but in vitro and animal studies have suggested that equol and O-DMA are more biologically active than their precursor daidzein. Interestingly, substantial interindividual differences in daidzein metabolism exist; following soy or daidzein consumption, approximately 30%-50% of the human population produce equol, and approximately 80%-90% produce O-DMA. Observational and intervention studies in humans have suggested that the ability to produce equol and O-DMA may be associated with reduced risk of certain diseases including breast and prostate cancers. However, relatively few studies have been conducted to date. In this review, we discuss the available evidence for a relationship between daidzeinmetabolizing phenotypes and human health, and suggest potential mechanisms for some of the reported relationships.
The structural analogs of bisphenol A (BPA) and their halogenated derivatives (together referred as BPs) have been found in environment, food and even human. Limited research showed that some of them exhibited similar to or even greater toxicities than BPA. Therefore, adverse effects on humans with low-dose in early life exposure were expected for BPs. Breast milk is an excellent matrix could reflect fetus and babies exposure to contaminants. Some of the emerging BPs may present with trace or ultra-trace levels in human. However, the existing analytical method in breast milk cannot quantify these BPs simultaneously with highly sensitivity using small sampling weight, which is important for human biomonitoring study. In this paper, a method based on Bond Elut Enhanced Matrix Removal-Lipid purification, pyridine-3-sulfonyl chloride derivatization and liquid chromatography electrospray tandem mass spectrometry was developed. The method required only small quantity of sample (200 μL) and allowed for the simultaneous determination of 24 BPs in breast milk with ultra high sensitivity. The limit of quantifications of the proposed method were 0.001-0.200 μg L-1, which were 1-6.7 times lower than the only study for the simultaneous analysis of bisphenol analogs in breast milk based on 3 g sample weight. The mean recoveries ranged from 86.11% to 119.05% with relative standard deviations (RSD) ≤ 19.5% (n = 6). Matrix effects were within 20% with RSD < 10% for 6 different lots of samples. The proposed method was successfully applied to 20 breast milk samples. BPA, bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF) were detected. BPA was still the dominant BPs following by BPF in the second place. This is the first time describing the occurrence of BPF and BPAF in breast milk.
Bisphenols (BPs) are a family of chemicals with known endocrine disrupting activity. Bisphenol A (BPA) is the most representative prototype of this group of chemicals. Recently, the use of BPA, a prototype of endocrine disruptors, has been reduced and replaced with structural analogs due to its negative effects on both the environment and consumers. In this work, a new method is presented for the determination of seven BPs, with estrogenic activity in ready-to-eat plastic packaged baby foods. The procedure involves the isolation of the analytes using solid-liquid phase extraction with acetonitrile followed by a clean-up step with a mixture of dispersive-SPE sorbents (C18 and PSA) and magnesium sulphate, to reduce matrix effect from proteins, sugars and lipids. Extraction parameters were optimized using multivariate optimization methods. The compounds were detected and quantified by gas chromatography tandem mass spectrometry (GC–MS/MS). The limits of quantification were between 0.1 and 1.2 ng g⁻¹ for the studied analytes. The method was validated using matrix–matched calibration and recovery assays with spiked samples. Recovery rates were between 91% and 110% and % RSD was lower than 13% in all cases. The method has been successfully applied for the determination of these endocrine disrupting chemicals (EDCs) in samples of a novel type of food consumed by pre-schoolers. This is the first study to analyze EDCs in plastic packaged foods consumed by this target group.
Aims:
Obesity is one of the most significant global health and social problems, with rates rising dramatically over the past few decades. While the basic drivers of obesity are obvious (more energy consumed than expended), the causes are multifactorial and complex. A decade ago, it was suggested that exploring the ways in which the built environment influenced physical activity and dietary behaviours might provide fertile ground for investigation. This article overviews current evidence and, in particular, emergent themes that are of significance for the United Kingdom.
Methods:
This article is based on literature extracted from keyword searching of electronic databases. A timeframe of 2006–2016 was used.
Results:
In the past decade, the research base has grown significantly; while frustratingly some results are still inconclusive or contradictory, it might be argued enough evidence exists to act upon. Themes such as the importance of the journey to school for young people and the multiple environments in which people spend their time are examples of where real progress has been made in the evidence base.
Conclusion:
Progress towards real change in policy and practice may seem slow; however, the opportunities afforded for health and planning professionals to work together provide a step towards the whole systems approaches to tackle obesity that are desperately needed.
Young children, whose growth and development are highly dependent on the endocrine system, are particularly vulnerable to endocrine disruptor exposure. The main objectives of this study were to measure BPA migration levels from cans, fruit juice bottles/packs, and microwave containers used for food/drinks consumed by a sample of 6- to 8-year old schoolchildren in Spain and to estimate the relationship between their resulting BPA exposure and diet quality index scores (Mediterranean Diet Score and Breakfast Quality Index). The mean BPA concentration was 11.8 ng/mL for vegetable cans, 22.1 ng/mL for pulse cans, 3.6 ng/mL for juice bottles/packs, and 1.2 ng/mL for microwave containers. Results revealed a significant association between the Mediterranean Diet Score and low BPA exposure of the children. BPA exposure below the median level was significantly associated with a higher score in both the first-grade (P = 0.030) and second-grade (p = 0.0001) groups. However, no association was found between BPA exposure and the Breakfast Quality Index. In conclusion, children with a stronger adherence to a Mediterranean-like diet appear to be less exposed to BPA migrating from food packaging and microwave containers. Further research is warranted on the inadvertent exposure of children to endocrinedisrupting chemicals from these sources.
Xenoestrogens are defined as exogenous substances that mimic the action of estrogens. They may have a role in the dietary etiology of human diseases and account for some fraction of unexplained cases of breast cancer. Animal and epidemiological studies have pointed out a chemopreventive action on mammary carcinogenesis by a particular group of foreign estrogens; these include phytoestrogens, a class of naturally occurring plant components that humans consume daily. Phytoestrogens have several anticarcinogenic biological activities that could account for their role in the etiology of breast cancer. Phytoestrogens are believed to exert their action by interacting with the estrogen receptor (alpha and beta forms), either triggering a specific response (agonist effect) or blocking the binding of stronger endogenous estrogens (antagonist effect). Other effects on protein synthesis, growth factor actions, malignant cell proliferation, angiogenesis, calcium transport, vascular smooth muscle cells, lipid oxidation and cell differentiation may also explain a protective role for phytoestrogens in breast cancer. The rise in breast cancer incidence has been related to the Western life-style. Dietary intakes of energy, fat, meat, milk, fish, fiber and fresh vegetables have been evaluated as contributing factors. Epidemiological investigations have related the urinary excretion of phytoestrogens to the incidence of breast cancer. In Asian countries the vegetarian diet seems to contribute to a low incidence of breast cancer. Thus, a role for phytoestrogens in the prevention of breast cancer is plausible.
Phyto-oestrogens are a family of plant-derived xeno-oestrogens that have been shown to prevent cancer in some studies. Whether phyto-oestrogen intake affects obesity status in a population is still unclear. In the present cross-sectional study, we examined the association of urinary phyto-oestrogen metabolites with obesity and metabolic parameters in children and adults. Data from 1294 children (age 6-19 years) and from 3661 adults (age ≥ 20 years) who participated in the US National Health and Nutrition Examination Survey 2001-10 were analysed. Multivariate logistic regression was applied to investigate the associations of BMI, waist circumference, serum metabolites (total cholesterol, HDL-cholesterol, LDL-cholesterol, TAG, fasting glucose and fasting insulin) and the metabolic syndrome with urinary phyto-oestrogen levels. When stratified by age and sex, we found a stronger association (OR 0·30, 95 % CI 0·17, 0·54; P< 0·001) between urinary enterolactone levels and obesity in adult males (age 20-60 years) than in children (age 12-19 years) or the elderly (age >60 years) in the same survey. However, no associations with urinary daidzein, O-desmethylangolensin, equol, enterodiol or genistein were found in the overall population. We also found that the elevation of enterolactone levels was inversely associated with TAG levels, fasting glucose levels, fasting insulin levels and the metabolic syndrome in males aged 20-60 years, but positively associated with HDL-cholesterol levels. The present results provide epidemiological evidence that urinary enterolactone is inversely associated with obesity in adult males.
Bisphenol A (BPA) is a synthetic compound with structural similarities to the hormone 17β-estradiol. BPA is a major component of polycarbonate plastics and epoxy resins, which are used in the production of plastic containers, metal can linings, dental sealants, thermal receipt paper and household paper products. Incomplete polymerization of BPA as well as exposure to high temperatures and acidic or basic conditions can cause BPA monomers to leach from these products. Therefore, most people are exposed to BPA and levels have been quantified in human urine, blood, saliva, amniotic fluid, placental tissue, colostrum and breast milk.
BPA is a weak estrogen and is considered a potential endocrine disrupting compound in humans. Initially it was thought that BPA was rapidly conjugated and excreted from the body. However, free BPA has been detected in human samples indicating that humans are internally exposed to estrogenically active BPA. The length of time that free BPA remains in circulation in the body and the extent to which it accumulates in tissues, such as the breast, is unknown.
Given the known sources of BPA exposure, it is likely that lifestyle habits lead to varying levels of BPA exposure. Repeated use of products that contain or are packaged in materials with a high BPA content can lead to higher exposure rates. The same lifestyle choices resulting in high BPA exposure may also lead to high body mass index (BMI); for example, frequent consumption of carbonated soft drinks is associated with a high BMI in women and these beverages are often packaged in plastic bottles or metal cans that may contain BPA. Two recent studies have demonstrated a relationship between BPA levels in urine and obesity in adults and children.
Because of the difficulty in measuring BPA in a complex fatty matrix such as milk, few studies have reported on BPA levels in breast milk, and none have examined the relationship between BMI and BPA. In the present study we optimized a sensitive method for assessing free BPA in breast milk and determined whether the levels of BPA were related to characteristics including age, race, BMI, child's age, and number of children nursed. BPA was separated from breast milk samples from 21 nursing women in the U.S. by solid-phase extraction and subsequently analyzed by HPLC-MS/MS. Free BPA was detected in 71% (15/21) of the breast milk samples. The method detection limit in water was determined to be 0.11 ng/mL. Free BPA concentrations were detected ranging from below the method detection limit to 10.81 ng/mL (median 0.49, mean 3.06, SD 3.85 ng/mL). No statistical difference in BPA concentrations was observed between women with a low BMI (< 21.00, n = 10) and a high BMI (> 27.00, n = 11). However, there was a significant association between BPA concentration and race. Caucasian women (n = 14) had significantly higher levels of free BPA in their breast milk than non-Caucasian women (n = 7) (Two-tailed test: t = 2.54, p < 0.05).
Citation Format: Stephanie M. Zimmers, Eva P. Browne, Patrick O'Keefe, Douglas L. Anderton, David A. Reckhow, Kathleen F. Arcaro. Determination of free bisphenol A (BPA) concentrations in breast milk of U.S. women using a sensitive LC/MS/MS method. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2520. doi:10.1158/1538-7445.AM2013-2520
Bisphenol-A (BPA) is an endocrine disrupting chemical used in numerous consumer products, resulting in universal exposure in the United States. Prenatal exposure to BPA is associated with numerous reproductive and developmental effects in animals. However, little is known about human fetal exposure or metabolism of BPA during mid-gestation. In the present study, we present a new liquid chromatography-tandem mass spectrometry method to directly measure concentrations of BPA and two predominant metabolic conjugates - BPA glucuronide and BPA sulfate - in umbilical cord serum collected from elective 2nd trimester pregnancy terminations. We detected at least one form of BPA in all umbilical cord serum samples: BPA (GM 0.16; range <LOD-52.26 ng/mL), BPA glucuronide (GM 0.14; range <LOD-5.41 ng/mL) and BPA sulfate (GM 0.32; range <LOD-12.65 ng/mL). Levels of BPA ranged from less than 1/100th to over 400 times higher than levels of BPA in conjugated form. Although levels of BPA in conjugated form exceeded BPA levels in about 3/4 of the samples, BPA levels were higher in samples with Total BPA above the median. Our findings suggest universal fetal exposure to BPA in our study population, with some at relatively high levels, and we provide the first evidence of detectable BPA sulfate in mid-gestation fetuses.
The gut microbial environment (bacteria and metabolites) may have a role in obesity. Urinary enterolignan concentrations can provide a marker of interindividual differences in microbial environments. Analysis was conducted on 6806 individuals from 2003 to 2008 National Health and Nutrition Examination Survey data, and weight status, waist circumference groups and high- vs low-enterolignan concentration was evaluated using multinomial logistic regression, adjusted for personal and dietary factors. High-enterolignan concentrations were defined as the 90th percentile value and greater. High-enterodiol concentration was associated with 18% and 42% lower likelihood of being overweight and obese, respectively, and 48% lower likelihood of having high-risk waist circumference among adults. High-enterolactone concentration was associated with 24% and 64% lower likelihood of being overweight and obese, respectively. Age and sex were not modifiers of these associations. These results from a large human study population provide additional evidence supporting the microbiome-obesity relationship.European Journal of Clinical Nutrition advance online publication, 12 June 2013; doi:10.1038/ejcn.2013.107.
Phytoestrogens are natural components of plants consumed by humans. The hormonal activity of these substances has long been known. Various in vitro tests have demonstrated the agonistic or antagonistic estrogenic activity of some phytoestrogens. The objective of this study was to estimate the supply of isoflavones in the diet of a healthy adult female population and to assess its estrogenic effect. The diet was assessed by questionnaire and the estrogenicity of the estimated isoflavone content was tested by E-screen, finding a mean total estrogenic capacity of 0.129 × 10(-10) eq.E2 (12.9 pmol day(-1)), corresponding to a daily isoflavone intake of 265.8 μg day(-1). This study offers a preliminary insight into the phytoestrogen content of the diet of a healthy active population of Spanish women. The effects of this additional hormonal burden are highly controversial, and this approach to estimating dietary phytoestrogen intake of specific populations may help to elucidate its implications for human health.
The international (International Obesity Task Force; IOTF) body mass index (BMI) cut-offs are widely used to assess the prevalence of child overweight, obesity and thinness. Based on data from six countries fitted by the LMS method, they link BMI values at 18 years (16, 17, 18.5, 25 and 30 kg m(-2)) to child centiles, which are averaged across the countries. Unlike other BMI references, e.g. the World Health Organization (WHO) standard, these cut-offs cannot be expressed as centiles (e.g. 85th).
To address this, we averaged the previously unpublished L, M and S curves for the six countries, and used them to derive new cut-offs defined in terms of the centiles at 18 years corresponding to each BMI value. These new cut-offs were compared with the originals, and with the WHO standard and reference, by measuring their prevalence rates based on US and Chinese data.
The new cut-offs were virtually identical to the originals, giving prevalence rates differing by < 0.2% on average. The discrepancies were smaller for overweight and obesity than for thinness. The international and WHO prevalences were systematically different before/after age 5.
Defining the international cut-offs in terms of the underlying LMS curves has several benefits. New cut-offs are easy to derive (e.g. BMI 35 for morbid obesity), and they can be expressed as BMI centiles (e.g. boys obesity = 98.9th centile), allowing them to be compared with other BMI references. For WHO, median BMI is relatively low in early life and high at older ages, probably due to its method of construction.
The presence of endocrine disruptors bisphenol-A, bisphenol-A-dimethacrylate, bisphenol-A-diglycidyl-ether, phthalic-acid, dibutyl-phthalate, diethyl-phthalate and dioctyl-phthalate was determined in vegetable cans, baby bottles and microwaveable containers from the Mexican market. Gas-Chromatography-Mass-Spectrometry was used for the identification and High-Performance-Liquid-Chromatography with UV/Visible light and fluorescence detectors was used for the quantification. Endocrine disruptors were found in all samples. PA and DOP were the substances most commonly found, and maximum concentrations were 9.549 and 0.664 μg/kg, respectively from a jalapeno peppers can. Bisphenol A, phthalic-acid, bisphenol-A-dimethacrylate, bisphenol-A-diglycidyl-ether, dioctyl-phtalate and dibutyl-phthalate were found in baby bottles and microwaveable containers.
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.
Koreans generally consume high quantities of soybean-based foods that contain a variety of phytoestrogens, such as, daidzein, zenistein, and biochalin A. However, phytoestrogens are considered to be potential endocrine-disrupting chemicals (EDC), which interfere with the normal function of the hormonal and reproductive systems. Therefore, dietary exposure to soybean-based phytoestrogens is of concern for Koreans, and comparative dietary risk assessments are required between Japanese (high consumers) versus Americans (low consumers). In this study, a relative risk assessment was conducted based upon daily intake levels of soybean-based foods and phytoestrogens in a Korean cohort, and the risks of photoestrogens were compared with those posed by estradiol and other EDC. Koreans approximately 30-49 yr of age consume on average a total of 135.2 g/d of soy-based foods including soybean, soybean sauce, soybean paste, and soybean oil, and 0.51 mg/kg body weight (bw)/d of phytoestrogens such as daidzein and genistein. Using estimated daily intakes (EDI) and estrogenic potencies (EP), margins of safety (MOS) were calculated where 0.05 is for estradiol (MOS value <1, considered to exert a positive estrogenic effect); thus, MOS values of 1.89 for Japanese, 1.96 for Koreans, and 5.55 for Americans indicate that consumption of soybean-based foods exerted no apparent estrogenic effects, as all MOS values were all higher than 1. For other synthetic EDC used as reference values, MOS values were dieldrin 27, nonylphenol 250, butyl benzyl phthalate 321, bisphenol A 1000, biochanin A 2203, and coumesterol 2898. These results suggest that dietary exposure to phytoestrogens, such as daidzein and genistein, poses a relatively higher health risk for humans than synthetic EDC, although MOS values were all greater than 1.
Higher consumption of phytoestrogens might be protective against certain chronic diseases. Accurate quantification of habitual phytoestrogen intake is important for assessing associations between phytoestrogens and risk for certain diseases. The aim of this study was to estimate dietary intake of phytoestrogens in Dutch middle-aged and elderly women and to describe their main sources. Women were recruited between 1993 and 1997 and aged 50-69 y at enrollment (Prospect-EPIC; n = 17,357). A detailed food frequency questionnaire referring to the preceding year was filled in at recruitment. A literature search was conducted to obtain data regarding content of the isoflavones daidzein, genistein, formononetin, biochanin A, the coumestan coumesterol and the lignans matairesinol and secoisolariciresinol in relevant food items. Concentrations of each phytoestrogen in each food item were subsequently grouped by seven categories; group scores were multiplied by daily intakes of food items and then summed across food items to produce for each participant a total daily intake score for each phytoestrogen. Approximately 75% of participants were postmenopausal at recruitment. The mean age was 57 y. Geometric means of daily intake of daidzein, genistein, formononetin, biochanin A, coumesterol, matairesinol and secoisolariciresinol were 0.15, 0.16, 0.08, 0.001, <0.001, 0.07 and 0.93 mg, respectively. The main sources for isoflavones were peas and beans, nuts, grain products, coffee, tea and soy products. The main sources for coumestans were peas, beans and other vegetables. The main sources of lignans were grain products, fruit and alcoholic beverages (red and white wines). We conclude that intake levels of phytoestrogen in our study population are low; however, they are comparable with intake levels previously reported for other Western cohorts. In this population, phytoestrogen intake consisted largely of lignans.
The phytoestrogens are naturally occurring compounds that are part of many foods of plant origin and could therefore modulate aspects related hormones, such as type of antioxidant reactions, learning about intakes of these compounds in different populations clarify important aspects on their responses on the human body.
To evaluate the exposure of phytoestrogens through diet, in a sample of women of all ages belonging to the university community (teachers, students and administrative), residents in the province of Granada, Spain.
52 adult females, aged between 20 and 63 years completed a questionnaire individually Frequency of Food Consumption (FFQ) composed of a total of 144 foods. It weighted the total daily consumption of phytoestrogens standardizing these values referring to the daidzein as substance pattern (mg/day). Statistical analysis was performed using SPSS 15.0 (SPSS Inc., Chicago, IL, USA), with a level of significance of p < 0.05.
The results show that the total intake of phytoestrogens was (0.89 mg/day), and most of phytoestrogens was consumed in the form of lignanos. The total consumption of isoflavones, was 0.12 mg/day, of lignanos was 1.32 mg/day intake coumestrol was not significative. A linear regression analysis determined the equation to calculate intake phytoestrogens took into account 9 food groups (R: 0.918; p < 0.001).
Average intake of phytoestrogens in Spain, is comparable to intakes reported by similar studies in Germany, England and the United States (< 1 mg/ day). Conclusions: There were no significant differences in the intake of phytoestrogens, when comparing results by age, educational level, marital status or physical activity. The intake of phytoestrogens (mg/day) can be estimated from the intake (g/day) from 9 food groups.
Non-prescription remedies are becoming increasingly popular particularly amongst postmenopausal who in this market are the largest consumers. Phytoestrogens are a large family of plant derived molecules possessing various degrees oestrogen like activity. Food or food supplements containing phytoestrogen are often been advocated as an alternative to hormonal replacement therapy (HRT) in women with contraindications to the use of conventional oestrogen replacement, or simply wanting a more 'natural' alternatives. There have been several studies performed with phytoestrogen in various aspects of the postmenopausal women health. Results have been sometimes conflicting and difficult to interpret. The lack of knowledge of what precisely is the active ingredient, its minimally effective doses, the lack of standardisation of the preparations used as well as the large individual variability of metabolism of precursors introduced with the diet may all have played a role in confusing the issue about effectiveness of these compounds. Phytoestrogen fall in the gray area between food and drugs hence in spite of the vast public interest, there are no interests in company producing these supplements in investing in research from which they will not exclusively benefit from. It is difficult for the physician to know how to advise patients on this matter. In this paper we critically review the clinical data available to date in an attempt to answer some of the most commonly asked questions about dose and type of phytoestrogens supplementation most likely to be effective in different aspects of climacteric woman health.
Bisphenol-A (BPA), material for polycarbonate and epoxy resin synthesis, has been detected in canned food, among other food containers. In mammal studies, BPA transferred from mother to fetus, caused abnormality of reproductive organs, and advanced female puberty. BPA from canned food and microwave containers was analyzed using high performance liquid chromatography and gas chromatography-mass spectrometry. Population was cohort of mother-son pairs established at Granada University Hospital. Frequency of food consumption (including canned food) was studied with a semi-quantitative questionnaire. The most frequently consumed products were fish and juice cans, consumed 1-3 times/week by 34.7% and 22.3% of the study population, respectively. The women made little use of polymer microwave containers, 52.8% never using them and 45.9% using them <3 times/month. Estimated mean (standard deviation) intake of BPA was 1.1(0.839) microgram/day. No relationship was found between BPA exposure and maternal socio-demographic variables or newborn characteristics. This study offers the first estimate of BPA dietary intake by pregnant women in Southern Spain. The consumption of canned foods and drinks by these women means that their exposure was lower than EFSA estimates for the European population. Nevertheless it remains of concern, given the proven undesirable effects of low-level exposure and higher susceptibility of pregnant women.
MCF7 human breast cancer cells have been studied extensively as a model for hormonal effects on breast cancer cell growth and specific protein synthesis. Because the proliferative effect of natural estrogen is considered the hallmark of estrogen action, it was proposed that this property be used to determine whether a substance is an estrogen. The E-screen assay, developed for this purpose, is based on the ability of MCF7 cells to proliferate in the presence of estrogens. The aim of our study was to characterize the response of four MCF7 cell stocks (BUS, ATCC, BB, and BB104) and determine which of them performed best in the E-screen test. The four stocks assayed were distinguishable by their biological behavior. In the absence of estrogen, MCF7 BUS cells stopped proliferating and accumulated in the G0/G1 phase of the cell cycle; estrogen receptors increased, progesterone receptors decreased, and small amounts of pS2 protein were secreted. Of all the MCF7 stocks tested, MCF7 BUS cells showed the highest proliferative response to estradiol-17 beta: cell yields increased up to sixfold over those of nontreated cells in a 144-hr period. The differences between estrogen-supplemented and nonsupplemented MCF7 BUS cells were due mostly to G0/G1 proliferative arrest mediated by charcoal dextran-stripped serum. MCF7 BUS cell stocks and others showing a similar proliferative pattern should be chosen for use in the E-screen test, or whenever a proliferative effect of estrogen is to be demonstrated.
Because many diseases of the Western Hemisphere are hormone-dependent cancers, we have postulated that the Western diet, compared to a vegetarian or semivegetarian diet, may alter hormone production, metabolism, or action at the cellular level by some biochemical mechanisms. Recently, our interest has been mainly focused on the cancer-protective role of some hormonelike diphenolic phytoestrogens of dietary origin, the lignans and the isoflavonoids. The precursors of the biologically active compounds originate in soybean products (mainly isoflavonoids), whole grain cereal food, seeds, and probably berries and nuts (mainly lignans). The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormonelike compounds with weak estrogenic but also antioxidative activity; they have now been shown to influence not only sex hormone metabolism and biological activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation, and angiogenesis in a way that makes them strong candidates for a role as natural cancer-protective compounds. Epidemiologic investigations strongly support this hypothesis because the highest levels of these compounds in the diet are found in countries or regions with low cancer incidence. This report is a review on recent results suggesting that the diphenolic isoflavonoids and lignans are natural cancer-protective compounds.
Incidences of breast, colorectal and prostate cancer are high in the Western world compared to countries in Asia. We have postulated that the Western diet compared to the semivegetarian diet in some Asian countries may alter hormone production, metabolism or action at the cellular level by some biochemical mechanisms. Our interest has been focused on two groups of hormone-like diphenolic phyto-oestrogens of dietary origin, the lignans and isoflavonoids abundant in plasma of subjects living in areas with low cancer incidence. The precursors of the biologically active compounds detected in man are found in soybean products, whole-grain cereal food, seeds, and berries. The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like compounds. The weakly oestrogenic diphenols formed influence sex-hormone production, metabolism and biological activity, intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation, cell adhesion and angiogenesis in such a way as to make them strong candidates for a role as natural cancer-protective compounds. Their effect on some of the most important steroid biosynthetic enzymes may result in beneficial modulation of hormone concentrations and action in the cells preventing development of cancer. Owing to their oestrogenic activity they reduce hot flushes and vaginal dryness in postmenopausal women and may to some degree inhibit osteoporosis, but alone they may be insufficient for complete protection. Soy intake prevents oxidation of the low-density lipoproteins in vitro when isolated from soy-treated individuals and affect favourably plasma lipid concentrations. Animal experiments provide evidence suggesting that both lignans and isoflavonoids may prevent the development of cancer as well as atherosclerosis. However, in some of these experiments it has not been possible to separate the phyto-oestrogen effect from the effect of other components in the food. The isoflavonoids and lignans may play a significant inhibitory role in cancer development particularly in the promotional phase of the disease, but recent evidence points also to a role in the initiation stage of carcinogenesis. At present, however, no definite recommendations can be made as to the dietary amounts needed for prevention of disease. This review deals with all the above-mentioned aspects of phyto-oestrogens.
For the past two decades, epidemiologists have observed lower risks of lung, breast, prostate, colon, and other cancers in populations that frequently consume fruits and vegetables. Numerous phytoestrogens have been shown to be anticarcinogenic under experimental conditions and may account for at least part of the cancer-prevention effects of fruit and vegetable consumption. These plant constituents include isoflavonoids, coumestans, lignans, phytosterols, and flavonoids. DietSys, the nutrient analysis program associated with the National Cancer Institute Health Habits and History Questionnaire (HHHQ), and other nationally available nutrient analysis databases do not fully assess these constituents. Therefore, we modified DietSys to include these components in foods on the basis of published values. In addition, as part of an epidemiological study of prostate cancer, we modified the food-frequency component of the HHHQ to include the main foods contributing to phytoestrogen intake. Although there are limitations to the consistency and quality of many of the values because they were gathered from a variety of sources, our approach should provide a useful first tool for assessing the epidemiological association between phytoestrogen consumption and cancer risk. Furthermore, this work has already facilitated the identification of the major dietary contributors with phytoestrogen activity and prioritized future laboratory analyses of specific foods toward the development of a more complete and accurate database.
Phytoestrogens (weak estrogens found in plants or derived from plant precursors by human metabolism) have been hypothesized to reduce the risk of a number of cancers. However, epidemiologic studies addressing this issue are hampered by the lack of a comprehensive phytoestrogen database for quantifying exposure. The purpose of this research was to develop such a database for use with food-frequency questionnaires in large epidemiologic studies.
The database is based on consumption patterns derived from semistructured interviews with 118 African-American, Latina, and white women residing in California's San Francisco Bay Area. HPLC-mass spectrometry was used to determine the content of seven specific phytoestrogenic compounds (i.e. the isoflavones: genistein, daidzein, biochanin A, and formononetin; the coumestan: coumestrol; and the plant lignans: matairesinol and secoisolariciresinol) in each of 112 food items/groups.
Traditional soy-based foods were found to contain high levels of genistein and daidzein, as expected, as well as substantial amounts of coumestrol. A wide variety of "hidden" sources of soy (that is, soy protein isolate, soy concentrate, or soy flour added to foods) was observed. Several other foods (such as various types of sprouts and dried fruits, garbanzo beans, asparagus, garlic, and licorice) were also found to be substantial contributors of one or more of the phytoestrogens analyzed.
Databases, such as the one described here, are important in assessing the relationship between phytoestrogen exposure and cancer risk in epidemiologic studies. Agencies, such as the United States Department of Agriculture (USDA), that routinely provide data on food composition, on which epidemiologic investigations into dietary health effects are based, should consider instituting programs for the analysis of phytochemicals, including the phytoestrogens.
To study dietary intake and serum concentrations of isoflavones in order to provide relative validation of isoflavone intake estimates from the Scottish Collaborative Group - Food-Frequency Questionnaire (SCG-FFQ).
Validation study.
Southern Scotland.
Dietary intake of isoflavones was estimated using the semiquantitative SCG-FFQ and rank correlation and Kappa statistics were used for the relative validation of intakes against serum isoflavone concentrations in 203 male participants who were population controls in a case-control study of diet and prostate cancer.
The median intake of isoflavones (daidzein and genistein) was 1.0mg/day (l-QR 0.6-1.8). The median serum concentration of genistein was 33.79 nmol/l (I-QR 14.12-64.93), nearly twice that of daidzein (18.00 nmol/l, I-QR 8.26-29.45). Equol was detected in 49% of subjects; in these subjects the median was 0.67 nmol/l (I-QR 0.34-1.51). Isoflavone intake was significantly correlated with serum concentrations of daidzein (p = 0.24, P = 0.001), genistein (p = 0.26, P < 0.001) and total isoflavonoids (sum of daidzein, genistein and equol) ( p = 0.27, P < 0.001). Whereas values for weighted Kappa ranged from 0.16 (P = 0.002) for daidzein and equol combined to 0.22 (P < 0.001) for genistein.
These results demonstrate the suitability of the SCG-FFQ to rank usual isoflavone intakes in older Scottish men, a population observed to have low consumption of soy foods.
Urolithins A and B (hydroxy-6H-dibenzo[b,d]pyran-6-one derivatives) are colonic microflora metabolites recently proposed as biomarkers of human exposure to dietary ellagic acid derivatives. Molecular models suggest that urolithins could display estrogenic and/or antiestrogenic activity. To this purpose, both urolithins and other known phytoestrogens (genistein, daidzein, resveratrol, and enterolactone) were assayed to evaluate the capacity to induce cell proliferation on the estrogen-sensitive human breast cancer MCF-7 cells as well as the ability to bind to alpha- and beta-estrogen receptors. Both urolithins A and B showed estrogenic activity in a dose-dependent manner even at high concentrations (40 mu M), without antiproliferative or toxic effects, whereas the other phytoestrogens inhibited cell proliferation at high concentrations. Overall, urolithins showed weaker estrogenic activity than the other phytoestrogens. However, both urolithins displayed slightly higher antiestrogenic activity (antagonized the growth promotion effect of 17-beta-estradiol in a dose-dependent manner) than the other phytoestrogens. The IC50 values for the ER alpha and ER beta binding assays were 0.4 and 0.75 mu M for urolithin A; 20 and 11 mu M for urolithin B; 3 and 0.02 for genistein; and 2.3 and 1 for daidzein, respectively; no binding was detected for resveratrol and enterolactone. Urolithins A and B entered into MCF-7 cells and were metabolized to yield mainly urolithin-sulfate derivatives. These results, together with previous studies regarding absorption and metabolism of dietary ellagitannins and ellagic acid in humans, suggest that the gut microflora metabolites urolithins are potential endocrine-disrupting molecules, which could resemble other described "enterophytoestrogens" (microflora-derived metabolites with estrogenic/antiestrogenic activity). Further research is warranted to evaluate the possible role of ellagitannins and ellagic acid as dietary "pro-phytoestrogens".