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Phytoestrogen Content of Foods Consumed in Canada, Including Isoflavones, Lignans, and Coumestan
Abstract
Phytoestrogens may play a role in hormone-related diseases such as cancer, but epidemiological and clinical data are conflicting in part due to inadequate databases used in intake estimation. A database of nine phytoestrogens in foods relevant to Western diets was developed to more accurately estimate intakes. Foods (N = 121) available in Ontario, Canada were prepared as commonly consumed and analyzed for isoflavones (genistein, daidzein, glycitein, formononetin), lignans (secoisolariciresinol, matairesinol, pinoresinol, lariciresinol), and coumestan (coumestrol) using gas chromatography-mass spectrometry methods. Data were presented on an as is (wet) basis per 100 g and per serving. Food groups with decreasing levels of total phytoestrogens per 100 g are nuts and oilseeds, soy products, cereals and breads, legumes, meat products, and other processed foods that may contain soy, vegetables, fruits, alcoholic, and nonalcoholic beverages. Soy products contain the highest amounts of isoflavone, followed by legumes, meat products and other processed foods, cereals and breads, nuts and oilseeds, vegetables, alcoholic beverages, fruits, and nonalcoholic beverages. Decreasing amounts of lignans are found in nuts and oilseeds, cereals and breads, legumes, fruits, vegetables, soy products, processed foods, alcoholic, and nonalcoholic beverages. The richest sources of specific phytoestrogens, including coumestrol, were identified. The database will improve phytoestrogen intake estimation in future epidemiological and clinical studies particularly in Western populations.
... A study of the hereditary polygenic background of sugar content revealed that this environmental factor prevails. Wood from almond hulls comprises cellulose, hemicellulose and lignin, which account for 50-80% of the whole fiber content [26]. Notably, different methods have been used for the determination of fiber content by applying main nitrogen fertilizer, sulfuric acid, crude fiber and total dietary fiber, which affect the values received. ...
... Compared with almond kernels, which are rich in fat-soluble vitamins [26,28], almond kernels provide an excellent supply of vital nutrients [12,20]. The majority of the studies provide data on major elements. ...
... The combined effects of two factors, drought and heat, are related to the increase in α-tocopherol contents in the cultivars. This property was evidenced in several investigations that were carried out on almonds cultivated in Morocco, Afghanistan and Argentina (Northwest) [26,31]. Additionally, the year of collection determines the accuracy of the results. ...
The main aim of this chapter is to present a short summary of different growing species of almond and their health benefits. “Almonds,” which are cherished for their taste and nutritional value, are available in dozens of varieties, each possessing its own distinct character. The nutritional composition of almond is presented through our analysis, which highlights the macronutrient, micronutrient, fiber and phytochemical contents. Popular almond types, which include Nonpareil, Carmel, Mission, Sonora, and Independence, along with their freshest taste and implementation in cooking, are described. In addition, we provide information on the health benefits of almond, such as its benefits for heart health, weight management, blood sugar control, bone health and brain health. In human food preparation, almonds are not only combined with snacks but also in other simple mixed dishes, bakes, beverages and comprehensive options. The choice of almond variety depends on the nutritional value and culinary possibilities of distinct varieties of almond. Genetically and environmentally friendly, the nutritional quality of almond may vary slightly. It is known for several pharmacological properties, including antistress, antioxidant, immune stimulant, lipid strategizing and laxative properties. It is a highly useful tool for improving the health of our memory, ameliorating muscle function, prolonging life, and improving various other aspects of our health.
... Isoflavones are widely present in both human and animal food. Unlike the majority of flavonoids, isoflavones, including genistein (7,4′-dihydroxy-6-methoxyisoflavone), daidzein (7,4′-dihydroxyisoflavone), glycitein (7,4′-dihydroxy-6-methoxy isoflavone), biochanin A (5,7-dihydroxy-4′-methoxyisoflavone), and formononetin (7-hydroxy-4 -methoxyisoflavone), are present only in a selected group of plant species, including legumes belonging to the Fabaceae family, other edible legumes, and certain types of nuts (Mazur 1998; Thompson et al. 2006). Soya (Glycine max) is the main source of daidzein, genistein, and glycitein and stand out as the primary reservoir of isoflavones, containing approximately 1 g of these compounds per kilogram of fresh weight (Thompson et al. 2006). ...
... Unlike the majority of flavonoids, isoflavones, including genistein (7,4′-dihydroxy-6-methoxyisoflavone), daidzein (7,4′-dihydroxyisoflavone), glycitein (7,4′-dihydroxy-6-methoxy isoflavone), biochanin A (5,7-dihydroxy-4′-methoxyisoflavone), and formononetin (7-hydroxy-4 -methoxyisoflavone), are present only in a selected group of plant species, including legumes belonging to the Fabaceae family, other edible legumes, and certain types of nuts (Mazur 1998; Thompson et al. 2006). Soya (Glycine max) is the main source of daidzein, genistein, and glycitein and stand out as the primary reservoir of isoflavones, containing approximately 1 g of these compounds per kilogram of fresh weight (Thompson et al. 2006). Furthermore, red clover (Trifolium pratense L.) boasts elevated concentrations of isoflavones including formononetin and biochanin A (Křížová et al. 2019) and is also harnessed as a dietary enhancement (Dornstauder et al. 2001). ...
In Western countries, the increase in the consumption of soy-derived products raises the population's exposure to isoflavones. These molecules, present in many foods, have numerous effects on the body's cells, including regulation of the transcription and epigenetics, cell signaling, cell cycle, cell growth, apoptosis, and oxidative stress. However, despite the multitude of studies conducted, on these compounds, it remains difficult to draw definitive conclusions regarding their safety or dangerousness in the diet. Indeed, some epidemiological studies highlight health benefits in consuming isoflavone-rich foods, notably by reducing the risk of certain cancers. However, several studies conducted on cell models show that these molecules can have negative effects on cell fate, particularly with regard to proliferation and survival of mammary tumor cells. Isoflavones are mainly genistein, daidzein, formononetin, and biochanin A. These molecules belong to the family of phytoestrogens, which are capable of interacting with both nuclear estrogen receptor, ERα and ERβ, to trigger agonistic and antagonistic effects. Due to their estrogenic properties, isoflavones are suspected to promote hormone-dependent cancers such as breast cancer. This suspicion is based primarily on their ability to bind to ERα in breast cells, thereby altering the signaling pathways that control cell growth. However, study results are sometimes contradictory. Some studies suggest that isoflavones may protect against breast cancer by acting as selective estrogen receptor modulators, while others highlight their potential role in stimulating tumor growth. This review explores the literature on the effects of isoflavones, focusing on their influence on ERα-dependent signaling in breast tumor cells.
... Lignan precursors are found in most plants but primarily in flaxseed, legumes, fruits, vegetables, and whole grains [23,24]. Most, but not all [25], studies have shown no association between lignan supplementation and hot flashes [26][27][28][29][30]. Foods high in coumestrol, a type of coumestan, include alfalfa and clover sprouts, split peas, and pinto beans. ...
... b Most phytoestrogen, isoflavone, and lignan values from Kuhnle et al. (2009) [67]. Values for nuts and seeds from Thompson et al. (2006). c Isoflavones are the sum of daidzein, genistein, glycitein, biochanin A and formononetin (Kuhnle et al. 2009). ...
There is a longstanding interest in the relationship between diet and hot flash symptoms during midlife, especially in whether phytoestrogens ease menopausal symptoms. The purpose of this study was to examine hot flashes, night sweats, trouble sleeping, and vaginal dryness in relation to the intake of foods rich in phytoestrogens among Bangladeshi women aged 35 to 59 years who were living either in Sylhet, Bangladesh (n = 157) or as migrants in London (n = 174). Consumption ranges for phytoestrogens were constructed from food frequencies. We hypothesized that diets rich in isoflavones, lignans, and coumestrol would be associated with lower symptom frequencies. However, adjusted logistic regression results showed that with each incremental increase in general phytoestrogen consumption (scale of 0 to 10), the likelihood of hot flashes increased by 1.4%. Each incremental increase in lignan consumption raised the likelihood of hot flashes by 1.6%. In contrast, the odds of vaginal dryness decreased by 2%, with each incremental increase in phytoestrogen and lignan consumption, and by 4%, with each incremental increase in isoflavone consumption. Night sweats and trouble sleeping were not associated with phytoestrogen intake in logistic regressions. Our findings add to the conflicting data on relationships between phytoestrogens and symptoms associated with menopause.
... Pinoresinol, daidzein, coumesterol, formononetin, glycitein stigmasterol, genistein, matairesinol, secoisolariciresinol, lariciresinol, esterone, ergosterol, estrogen and campesterol, brassicasterol, , isofucosterol, and β-sitosterol and five-triterpenoid lupeol (lup-20 (29) en-3P-0l) stigmasta-5,22-diane-3-a, β-sitosterol, lupeol 24-methylene clenchlortanol, 24-(Erubidenin-3-a), sigmastan-5-5-diene, and cholesterol-4-n -3-, 4-methylcholest-4-en-3-one, stigmast-4-en-3-1, spinasterone and cholesta-3,5-diene. (Kikuchi and Miki, 1978;Duke 2001;Thompson et al., 2006;Liolios et al., 2009;Al-Abid 2012;Maqsood et al., 2020). ...
... A different investigation determined several phytoestrogen compounds in date fruit, including genistein, daidzein, secoisolariciresinol glycitein, coumestrol, formononetin, lariciresinol, matairesinol, and pinoresinol (Thompson et al., 2006). ...
The date palm is widely known as a richer nutritional source and natural medical agent. Date fruit is a major source of carbohydrates and dietary fiber, and it has contains proteins, minerals, vitamins, phenolic compounds, carotenoids, sterols, and triterpenoids. The beneficial potential of this fruit is well known in Arab countries and even in the world. Date fruit has many health benefits such as Glucose-lowering potential, anti-cancer activity, antioxidant activity, hypocholesterolemia-lowering potential, antimicrobial activity, anti-inflammatory activity, bone stimulating activity, which is attributed to the existence of bioactive substances such as carotenoids, polyphenols, triterpenoids, flavonoids, sterols, and some vitamins and minerals. Overall, Arabian date palms’ nutritional values and pharmacological activities remain to be explained. Thus, this study states the history, nutritional and health effects of Arabian date palm, highlighting the possibility of palm date components developing novel beneficial approaches for managing the above mentioned illnesses. Keywords: Arabian date palm; Arab’s tree; Nutritional values; Pharmacological activities
... Phytoestrogens have been found in alfalfa, barley, corn, flax, oats, soybeans, and wheat, among other natural food components (Gupta & Prakash, 2014). The main phytoestrogen substances discovered in dietary supplements used in various animal nutrition laboratories are the isoflavones (daidzein, genistein, formononetin, and biochanin A) and coumestans (coumestrol; Thompson et al., 2006). Phytoestrogens are a plant product with a wide range of chemicals that are modified by species differences, plant section studied, geographic region, harvest time, and processing methods (Adlercreutz, 1995). ...
... Isoflavonoids are flavonoids in which one of the phenolic rings has shifted from C-3 to C-2. Legumes with isoflavones include soy, chickpeas, lentils, clover, and beans (Thompson et al., 2006 ...
Phytoestrogens are plant secondary metabolite that is structurally and functionally similar to mammalian estrogens, which have been shown to have various health benefits in humans. Isoflavones, coumestans, and lignans are the three major bioactive classes of phytoestrogens. It has a complicated mechanism of action involving an interaction with the nuclear estrogen receptor isoforms ERα and ERβ, with estrogen agonist and estrogen antagonist effects. Depending on their concentration and bio-availability in various plant sources, phytoestrogens can act as estrogen agonist or antagonists. Menopausal vasomotor symptoms, breast cancer, cardiovascular disease, prostate cancer, menopausal symptoms, and osteoporosis/bone health have all been studied using phytoestrogens as an additional standard hormone supplemental remedy. The botanical sources, techniques of identification, classification, side effects, clinical implications, pharmacological and therapeutic effects of their proposed mode of action, safety issues, and future directions for phytoestrogens have all been highlighted in this review. K E Y W O R D S coumestans, estrogen, isoflavones, lignans, phytoestrogen
... Furthermore, these diet types count on abundant amounts of phytoestrogens lignans and isoflavones, which are plant-derived estrogens less powerful than estradiol, but that are capable https://doi.org/10.1017/S0007114525000443 Published online by Cambridge University Press of binding to the estrogen receptor and reducing hot-flashes severity and frequency (9,31,32) . ...
The primary causes of female mortality often involve diseases related to oxidative stress. Dietary total antioxidant capacity (TAC) evaluates its antioxidant content and potential health effects. This study, registered with PROSPERO (ID: CRD42024427784), explores the association between dietary TAC and women’s health outcomes, including endocrine conditions with gynecological implications, obstetric outcomes, gynecological conditions, and oncological diseases related to the female reproductive system. We conducted a systematic search in MEDLINE (via PubMed), EMBASE, LILACS, and CINAHL for observational studies published up to February 2024 that explored the relationship between dietary TAC and these health conditions. Data were analyzed using RevMan 5.4 software. Nineteen studies met the eligibility criteria (sample sizes: 64 to 3,209 women) and examined various conditions, including neoplasms (breast, endometrial, and ovarian), bacterial vaginosis, menopause, polycystic ovary syndrome (PCOS), pre-eclampsia (PE), gestational diabetes mellitus (GDM), miscarriage, infertility, and inflammation and oxidative stress markers. The meta-analysis identified a significant association between dietary total antioxidant capacity (TAC), measured in vitamin C equivalents, and breast cancer, revealing that women with the disease had a lower dietary TAC due to reduced antioxidant intake. Mixed results were found for endometrial cancer, while higher TAC levels were associated with a lower risk of PCOS and infertility. Among postmenopausal women, higher TAC correlated with fewer symptoms such as sleep issues and anxiety. In gestational conditions, higher dietary TAC was linked to a lower risk of miscarriage, GDM, and PE. Twelve of the nineteen studies demonstrated significant associations between dietary TAC and the outcomes of interest.
... There are three phytoestrogens which are phenolic in nature and are known as coumestrol, lignin, isoflavones diadzine and genistein (Desmawati and Sulastri 2019). The food which is supposed to contain maximum concentration of phytoestrogen are oilseeds, nuts, breads, cereals, soy products, legumes, processed foods which comprises of fruits, vegetables and soy and beverages both alcoholic and nonalcoholic (Thompson et al. 2006). There are a number of medicinal herbs that contain phytoestrogens such as Shatavari (Asparagus racemosus), Brahmi (Bacopa monnieri), Punarnava (Boerhaavia diffusa), Vansha (Bambusa arundinaceae), Kumari (Aloe barbadensis), Triphala (Myrobalans), Shatavari (Asparagus racemosus), Vidari (Pueraria tuberose), Ashwagandha (Withania somnifera), Jayanti (Sesbenia sesban), Amalaki (Emblica officinalis Gaertn), Kumkum (Crocus sativus) and Mandukaparni (Centella asiatica) (Kulkarni and Khobragade 2016). ...
World Health Organization defines the drugs of herbal origin as medicinal agents that are mainly composed of the active constituents of plants or other plant material or combination of both of these. Although these agents are considered to be safe or exhibit lesser side effects, however a wide range of plants having medicinal value, the secondary metabolites of these plants have shown various toxic and poisonous effects. In the present review, the various toxic components have been discussed under different classes of herbs such as herbs containing alkaloids, glycosides, terpenoids and phytoestrogens, etc.
Graphical Abstract
... The levels vary within the same food group, e.g., soy beverages, depending on the process and type of soybeans used and soy-based products containing isoflavone. Plant-based products containing soya include miso, soymilk, edamame, and meat alternatives [7,41,42]. Dried fruits, such as dates, prunes, and dried apricots, are another good resource of phytoestrogens [28,43,44]. ...
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.
... L. [42,43]. [42][43][44][45][46]. The ubiquity of genistein in such a variety of plant species suggests that polyphagous herbivores such as the studied aphids may come into contact with this flavonoid while exploring the plants and feeding. ...
(1) Background: Genistein is a naturally occurring flavonoid with a rich spectrum of biological activities, including plant-herbivore interactions. The aim of the study was to evaluate the effect of exogenous application of genistein on aphid behavior during probing in plant tissues. (2) Methods: Vicia faba, Brassica rapa ssp. pekinensis, and Avena sativa were treated transepidermally with a 0.1% ethanolic solution of genistein, and the probing behavior of generalist aphid species Aphis fabae, Myzus persicae, and Rhopalosiphum padi was monitored on their respective treated and untreated host plants using electropenetrography (=electrical penetration graph technique, EPG); (3) Results: Genistein did not deter aphid probing activities in non-phloem tissues. In A. fabae and R. padi, a trend towards reduction and in M. persicae a trend towards increase in phloem sap ingestion occurred on genistein-treated plants, but these trends were not statistically significant. (4) Conclusions: Genistein is not a deterrent chemical against generalist aphid species studied; therefore, it is not recommended for practical application.
... The lignans are then extracted using organic solvents, typically ethanol, and supercritical fluid extraction and ultrasonicassisted extraction methods to improve efficiency [4,75,84,85,87]. Separation, quantification, and identification are usually carried out using high-performance liquid chromatography, chromatography-tandem mass spectrometry, nuclear magnetic resonance spectrometry, and other techniques [75,79,83,88,89]. In recent years, several methods have been used to extract lignans, with the yield and purity of the products varying in method-dependent manners. ...
Background: Flax (Linum usitatissimum L.) is the richest plant source of lignin secondary metabolites. Lignans from flax have been applied in the fields of food, medicine, and health due to their significant physiological activities. The most abundant lignan is secoisolariciresinol, which exists in a glycosylated form in plants. Results: After ingestion, it is converted by human intestinal flora into enterodiol and enterolactone, which both have physiological roles. Here, the basic structures, contents, synthesis, regulatory, and metabolic pathways, as well as extraction and isolation methods, of flax lignans were reviewed. Additionally, the physiological activity-related mechanisms and their impacts on human health, from the biosynthesis of lignans in plants to the physiological activity effects observed in animal metabolites, were examined. Conclusions: The review elucidates that lignans, as phenolic compounds, not only function as active substances in plants but also offer significant nutritional values and health benefits when flax is consumed.
... Sesame is usually con-sumed as a semiliquid paste, confectionery, or in desserts, and oil extracted from sesame seeds is commonly used as a cooking oil [13]. Sesame is rich in lignans [14,15], such as sesamin, sesamolin, sesamol, and sesaminol [16][17][18], comprising up to 1.5% of the weight of sesame seed or oil [13]. These lignans are converted metabolically by bacteria in the colon to mammalian lignans, enterodiol and enterolactone, which are structurally similar to human estrogen [17,19]. ...
Purpose: This animal experiment investigated how sesame seed (Sesamum indicum; SSI) extract affects bone metabolism in ovariectomized (Ovx) rats. Materials and methods: Female Wistar rats (12 weeks old) were randomly assigned to the Baseline control (BC), Sham, Ovx, and Ovx + SSI groups (n = 6-10). Animals in the BC group were sacrificed immediately. Rats in the other groups underwent sham surgery (Sham) or bilateral ovariectomy (Ovx and Ovx + SSI). Rats in the Ovx + SSI group were given custom diets, and BMD and bone histomorphometry were evaluated 13 weeks post-surgery. Results: The femur BMD in the Ovx + SSI group was lower than in the Ovx group, as were the measurements for bone formation rate and mineralizing surface. Conclusion: Administration of a methanol extract of sesame seeds decreased femur BMD in Ovx rats.
... 20 When compared to nuts and animal products, soybeans are one of the main sources of isoflavones, and they are also one of the best sources of these compounds. 21 ...
Soybean is scientifically known as Glycine max . It belongs to the Fabaceae family. It consists of a lot of bioactive phytochemicals like saponin, phenolic acid, flavonoid, sphingolipids and phytosterols. It also owns excellent immune‐active effects in the physiological system. Soy and its phytochemicals have been found to have pharmacological properties that include anticancer, antioxidant, anti‐hypercholesterolaemic, anti‐diabetic, oestrogenic, anti‐hyperlipidaemic, anti‐inflammatory, anti‐obesity, anti‐hypertensive, anti‐mutagenic, immunomodulatory, anti‐osteoporotic, antiviral, hepatoprotective, antimicrobial, goitrogenic anti‐skin ageing, wound healing, neuroprotective and anti‐photoageing activities. Present study has been designed to set standard pharmacognostical extraction method, complexation of compounds, qualitative evaluation through phytochemical screening, identification by TLC, physicochemical properties, solubility profile, total phenolic, flavonoid content as well as analytical evaluation or characterisation like UV and FT‐IR of methanolic extract of G. max . The final observations like physicochemical properties such as total ash value, LOD and pH were recorded. Phytochemical screenings show the presence of flavonoid, alkaloid, saponin, carbohydrate, tannins, protein, gums and mucilage, fixed oils and fats. The results were found significant. Further in silico studies proved creatinine and euparin to be potent wound healing agents.
... Specifically, only documents with publicly available abstracts on PubMed were selected, and these were further filtered based on the number of reported relations. Indeed, a manual inspection of a subset of articles revealed that documents reporting large numbers of relations (Swainston et al. 2016;Thiele et al. 2013;Stefanini et al. 2017;Thompson et al. 2006) often propose genome-scale metabolic reconstructions, large screening analyses, or database releases. Although these documents may report hundreds of relationships, they are typically not expressed in the abstracts, making them useless examples for building a RE model. ...
The sparsity of labeled data is an obstacle to the development of Relation Extraction (RE) models and the completion of databases in various biomedical areas. While being of high interest in drug-discovery, the literature on natural products, reporting the identification of potential bioactive compounds from organisms, is a concrete example of such an overlooked topic. To mark the start of this new task, we created the first curated evaluation dataset and extracted literature items from the LOTUS database to build training sets. To this end, we developed a new sampler, inspired by diversity metrics in ecology, named Greedy Maximum Entropy sampler (https://github.com/idiap/gme-sampler). The strategic optimization of both balance and diversity of the selected items in the evaluation set is important given the resource-intensive nature of manual curation. After quantifying the noise in the training set, in the form of discrepancies between the text of input abstracts and the expected output labels, we explored different strategies accordingly. Framing the task as an end-to-end Relation Extraction, we evaluated the performance of standard fine-tuning (BioGPT, GPT-2, and Seq2rel) and few-shot learning with open Large Language Models (LLMs) (LLaMA 7B-65B). In addition to their evaluation in few-shot settings, we explore the potential of open LLMs as synthetic data generators and propose a new workflow for this purpose. All evaluated models exhibited substantial improvements when fine-tuned on synthetic abstracts rather than the original noisy data. We provide our best performing (F1-score = 59.0) BioGPT-Large model for end-to-end RE of natural products relationships along with all the training and evaluation datasets. See more details at https://github.com/idiap/abroad-re.
... Flavonoids may be transported from the endoplasmic reticulum to different cellular compartments and their secretion to the plasma membrane and cell wall thanks to glycosylation, which also enhances solubility in the aqueous cellular environment and guards the reactive hydroxyl groups against autooxidation. Recent research demonstrates that the chloroplast and the nucleus of mesophyll cells, which are ROS production hubs, contain antioxidant flavonoids 26 . Here, they may quickly extinguish singlet oxygen, the hydroxyl radical, and H2O2. ...
Fruits, vegetables, grains, bark, roots, stems, flowers, tea, and wine all contain flavonoids, a class of organic compounds with varying phenolic structures. The health benefits of these natural compounds are widely recognised, and attempts are being undertaken to separate the so-called flavonoids from the other constituents. In a wide range of nutraceutical, pharmacological, therapeutic, and cosmetic uses, flavonoids are increasingly seen as an essential component. This is explained by their ability to influence the activity of essential cellular enzymes as well as their anti-oxidative, anti-inflammatory, anti-mutagenic, and anti-carcinogenic capabilities. With the revelation of the low cardiovascular death rate and also CHD prevention, research on flavonoids gained an additional boost. Uncertainty still exists regarding the flavonoids' functioning processes. However, it has long been understood that products with a plant origin have a wide range of biological activities. The separation, characterization, identification, and functions of flavonoids, as well as their applications for improved health, are the current developments in flavonoid research and development. Molecular docking and bioinformatics expertise are increasingly being utilised to forecast prospective industrial uses and production. In this study, efforts have been made to examine current flavonoid research and development trends, flavonoid modes of action, flavonoid functions, and flavonoid applications. It has also been predicted that flavonoids may one day be used as medications to prevent chronic illnesses.
... There are also other slightly outdated reports on the content of MATA in linseed. For instance, Mazur et al. [30] reported 10.87 µg/g FW, Thompson et al. [31] 1.53 µg/g FW, Milder et al. [32] found 5.53 µg/g FW, whereas Kraushofer & Sontag [33] measured seven samples where MATA content ranged from 7 to 28.5 µg/g FW. However, none of these authors specified the attributes of linseed samples (cultivar, year of harvest, location of growing). ...
Linseed represents a rich source of nutritional, functional and health-beneficial compounds. Nevertheless, the chemical composition and content of bioactive compounds may be quite variable and potentially affected by various factors, including genotype and the environment. In this study, the proximate chemical composition, lignans content and antioxidant potential of six experimentally grown linseed cultivars were assessed and compared. A diagonal cultivation trial in the University of South Bohemia Experimental Station in České Budějovice, Czech Republic, was established in three subsequent growing seasons (2018, 2019 and 2020). The results showed that the cultivar and growing conditions influenced most studied parameters. The lack of precipitation in May and June 2019 negatively affected the seed yield and the level of secoisolariciresinol diglucoside but did not decrease the crude protein content, which was negatively related to the oil content. The newly developed method for lignans analysis allowed the identification and quantification of secoisolariciresinol diglucoside and matairesinol. Their content correlated positively with the total polyphenol content and antioxidant assays (DPPH and ABTS radical scavenging activity), indicating the significant contribution to the biofunctional properties of linseed. On the other hand, we did not detect minor linseed lignans, pinoresinol and lariciresinol. The results of this study showed the importance of cultivar and growing conditions factors on the linseed chemical composition and the lignans content, determining its nutritional and medicinal properties.
... It exerts diverse estrogenic or anti-estrogenic effects [19]. Thompson et al. studied the phyto-estrogens content in DPD and they identified several phyto-estrogens which include: formononetin, daidzein, glycitein, genistein, matairesinol, lariciresinol, pinoresinol, and secoisolariciresinol [20]. ...
Phoenix dactylifera is an ancient tree that belongs to the Arecaceae family; its leaves, barks, fruits and pollens have highly anti-oxidant, anti-cancer, hepato-protective, neuro-protective, sexual improvement, anti-hyper lipidemic, and anti-microbial potentials. The broad pharmacological effects of Phoenix dactylifera may be attributed to the powerful and beneficial ingredients including phenolic, flavonoids, carotenoids, vitamins, minerals, amino acids, fatty acids and organic acids. The present review was conducted to describe the beneficial and pharmacological preventive effects of Phoenix dactylifera through recoded the published data on web of science, Scopus and Google scholar databases to review the pharmacological effects of Phoenix dactylifera.
... of the lignan secoisolariciresinol diglucoside (SDG) (2). The gut microbiota is necessary to convert SDG into the enterolignans enterodiol (ED) and enterolactone (EL) via the complementary action of members of the genera Bacteroides, Clostridium, Eubacteria ceae, Peptostreptococcus, Eggerthella, and Enterobacter (3). ...
The gut microbial ecosystem underlies physiological relationships between the gut and distal organs. Mechanisms remain elusive but rely at least partially on the production of a diverse set of absorbable metabolites and host gene expression regulation. Here we show that in female mice, gut cecal microbiota profiles are related to microRNAs (miRNAs) expressed in the mammary gland. A subset of these miRNAs were found to regulate genes involved in breast cancer-related processes, such as cell proliferation and migration. To determine if these relationships could be exploited toward the reduction of breast cancer risk, we studied if they are modifiable by dietary flaxseed (FS), a source of lignan secoisolariciresinol diglucoside (SDG) and alpha-linolenic acid (ALA)-rich oil (FSO), both with antitumor effects. Importantly, SDG, but not ALA, needs microbial processing to release bioactive metabolites. We found that the microbiota and mammary gland miRNA are related, and FS modifies these relationships toward an antioncogenic phenotype. FSO- and SDG-related miRNAs were found to be involved in different pathways and neither FSO nor SDG alone could recapitulate the effects of whole FS, affecting unique pathways related to extracellular matrix processing. These findings highlight the existence of inter-organ microbiota-miRNA relationships, show that dietary interventions interact to affect them, and suggest a novel route for breast cancer prevention.
IMPORTANCE
Breast cancer is a leading cause of cancer mortality worldwide. There is a growing interest in using dietary approaches, including flaxseed (FS) and its oil and lignan components, to mitigate breast cancer risk. Importantly, there is recognition that pubertal processes and lifestyle, including diet, are important for breast health throughout life. Mechanisms remain incompletely understood. Our research uncovers a link between mammary gland miRNA expression and the gut microbiota in young female mice. We found that this relationship is modifiable via a dietary intervention. Using data from The Cancer Genome Atlas, we also show that the expression of miRNAs involved in these relationships is altered in breast cancer in humans. These findings highlight a role for the gut microbiome as a modulator, and thus a target, of interventions aiming at reducing breast cancer risk. They also provide foundational knowledge to explore the effects of early life interventions and mechanisms programming breast health.
... Common carotenoids analyzed three different date fruit (Fard, , Khalas and Khasab) and confirmed that this variety was yellow due to haviey amounts of carotenoids, so Khalas, as predicted, was exposed to 4%-30% of the total carotenoid range after drying fruit (Al -Farsi et al., 2005a). Phytoestrogens have been identified such as silkworm, daidzein, genistein, glycine, Mata rechinol, lalithiresinol, mat phenol, sequoiol riccirecinol, and peppermint (Thompson et al., 2006). ...
Date palm (Phoenix dactylifera L.) is widely cultivated fruit tree having thousands of years of usage as food and medicinal plant. Its fruits, trunk and leaves contain a diverse array of phytochemicals with potential pharmacological activities. In recent years, the application of phytochemicals and biological active compounds, present in date palm, is getting attention of scientist to explore their role in the betterment of humans under malnutrition circumstances. The present review summarizes the current state of information on the phytochemicals and pharmacological activities of date palm tree. Phytochemicals found in date palm include polyphenols, flavonoids, carotenoids, tocopherols and triterpenoids. These compounds have been revealed with a wide range of anti-oxidant, anti-inflammatory, including biological activities and anti-tumor activities. Additionally, date palm has been found to have antidiabetic, hypolipidemic, and neuroprotective effects. These chemicals are also found affective against various diseases including cancer, cardiovascular issues and diabetes. These compounds have also been exposed to have cholesterol lowering anti-tumor effect and anti-inflammatory. In addition, the leaves of the date palm contain tannins, which have been found to have antimicrobial and antioxidant activities. The date palm’s fruit contains various bioactive compounds, including dietary fiber, vitamins, phenolic and minerals compounds. These compounds have been shown to have a range of health benefits, including improving gut health, reducing the stress of oxidative, and reducing the cardiovascular disease risk. Additionally, the fruit of the date palm has been found to have prebiotic effects, promoting the growth of beneficial gut bacteria.
... No published datasets were found for lignans, alkylresorcinols or phenolic acids in Australian products, but datasets were located for similar cereals and cereal products mainly from Europe, Canada and the UK 11,14,[55][56][57][58][59][60][61][62][63] (see Additional File 1). These data met the inclusion criteria for this study, values contained were all derived using chromatography, and have previously been used by other published studies developing ad-hoc databases 53,[64][65][66] . ...
Cereal foods are consumed globally and are important sources of polyphenols with potential health benefits, yet dietary intakes are unclear. We aimed to calculate the dietary intakes of polyphenols from cereal foods in the Melbourne Collaborative Cohort Study (MCCS), and describe intakes by demographic and lifestyle factors. We estimated intakes of alkylresorcinols, lignans and phenolic acids in n = 39,892 eligible MCCS participants, using baseline dietary data (1990–1994) from a 121-item FFQ containing 17 cereal foods, matched to a polyphenol database developed from published literature and Phenol-Explorer Database. Intakes were estimated within groups according to lifestyle and demographic factors. The median (25th–75th percentile) intake of total polyphenols from cereal foods was 86.9 mg/day (51.4–155.8). The most consumed compounds were phenolic acids, with a median intake of 67.1 mg (39.5–118.8), followed by alkylresorcinols of 19.7 mg (10.8–34.6). Lignans made the smallest contribution of 0.50 mg (0.13–0.87). Higher polyphenol intakes were associated with higher relative socio-economic advantage and prudent lifestyles, including lower body mass index (BMI), non-smoking and higher physical activity scores. The findings based on polyphenol data specifically matched to the FFQ provide new information on intakes of cereal polyphenols, and how they might vary according to lifestyle and demographic factors.
... Again few research articles witnessed improved menstrual cycles/regularity and increased progesterone secretion due to the supplementation of omega-3, [54] which could be another reason for flax seed recommendation in this diet. Similarly, negative effects or antiestrogenic effects of flax seed lignans were reported by several studies [55,56,57,58,59] . According to in-vitro and in-vivo studies, flax seed/ lignan (especially enterolactone) ingestion is associated with increased synthesis of sex hormone-binding globulin or sex steroid-binding globulin (SHBG) protein concentration [60,61] which can be a possible explanation for the antiestrogenic effect of lignan on menstrual cycle [62] . ...
The seed cycling/seed rotation diet is a new trend that claims to be effective for female menstrual dysfunctions such as irregular menstruation, menstrual cramps, infertility, menopausal symptoms (hot flashes, fatigue, etc.), and PCOS. The higher prevalence of hormonal imbalance in women is a contributing factor to all of these menstrual dysfunctions. The major hormones that control menstruation in females include progesterone, estrogen, luteinizing hormone (LH), and follicular stimulating hormone (FSH), and a simple imbalance in their concentration is the root cause of a variety of menstrual problems. The practice of eating specific seeds during the two main phases of the menstrual cycle (follicular and luteal) to promote a healthy balance of estrogen and progesterone levels in women is known as the seed rotation diet. During the follicular stage consumption of pumpkin seed and flax seed is advised and in the luteal stage consumption of sunflower seed and sesame seed is advised in this diet. Recent studies have shown that pumpkin seeds are rich in phytoestrogen which is a polyphenol compound that exerts a mammalian estrogenic-like effect in body. Similarly, flax seed in the first phase helps to bind the excess estrogen produced to maintain the hormonal homeostasis. Sesame seeds, which are high in zinc and lignans, are thought to help with progesterone balance during the luteal phase, while sunflower seeds, which are high in vitamin E and selenium aids in, increasing progesterone production and liver detoxification of excess estrogen. However, despite plenty of anecdotal accounts of its usefulness, scientific evidence to back its claims is still weak or lacking.
... Total phytoestrogen content ranged from 30.3 µg/100 g in raisins (seedless) to 445 µg/100 g in apricots. No phytoestrogens have been reported in dried apples, cranberries, figs, and peaches (Table 1) [11]. Detailed quantitative analysis on different classes of phenolic compounds, carotenoids, and phytoestrogens in different forms and varieties of dried fruits are needed. ...
Dried fruits contain many bioactive compounds broadly classified as phytochemicals including phenolics, flavonoids, carotenoids, proanthocyanidins, stilbenes, chalcones/dihydrochalcones, and phytoestrogens. These compounds have antioxidant effects that may benefit health. Dried fruits are also a diverse group of foods with varying fibre contents. The evaluation of the biological activity of these bioactive compounds, including their bioaccessibility and bioavailability, may contribute to the understanding of the health effects of dried fruits. Limited evidence suggests that dried fruits (raisins, cranberries, dates, and prunes) affect human gut microbiota composition in a potentially beneficial manner (in terms of effects on Bifidobacteria, Faecalibacterium prausnitzii, Lactobacillus, Ruminococcaceae, Klebsiella spp., and Prevotella spp.). There is little epidemiological evidence about the association of dried fruit consumption with cardiovascular disease incidence and mortality, as well as the risk of type 2 diabetes or obesity. Clinical trial evidence for the effects of dried fruit consumption on cardiovascular risk factors, including glycaemic control, is mixed. Clinical trial evidence suggests prunes might preserve bone mineral density in postmenopausal women. Consumption of dried fruits is associated with higher-quality diets. Studies are needed to increase our understanding of the health effects of dried fruits and the underlying biological mechanisms.
... Saryano and Rahmawati (2016) identified the phytosterols of dates as β-sitosterol, stigmasterol, campesterol and isofucosterol, while Thompson et al. (2006) studied the phytoestrogens content and they identified several phytoestrogens including formononetin, daidzein, genistein, glycitein, matairesinol, lariciresinol, pinoresinol, secoisolariciresinol, and coumestrol. Moreover, Boudries, Kefalas, and Hornero-Méndez (2007) analyzed the carotenoids content of three different varieties of dates at three stages of late ripening. ...
Appraised for being one of the oldest staple nutritive foods mainly in the Arabian Peninsula, the date palm tree (Phoenix dactylifera L.), is a crop native to the subtropical and tropical regions of Southern Asia and Africa. Different parts of the date tree have been extensively studied for their nutritional and therapeutic properties. Despite an array of publications on the date tree, there has been no attempt to compile in a single study the traditional uses, nutritive value, phytochemical profile, the medicinal properties as well as the potential of the different plant parts as a functional food. Therefore, this review endeavors to systematically review the scientific literature to highlight the traditional uses of date fruit and parts around the world, the nutritional profile of several parts and the medicinal properties. A total of 215 studies was retrieved (traditional uses (n = 26), nutritional (n = 52), and medicinal (n = 84)). Scientific articles were further categorized as in vitro (n = 33), in vivo (n = 35), and clinical (n = 16) evidences. Date seeds were found to be effective against E. coli and Staphylococcus aureus. Aqueous date pollen was used to manage hormonal problems and boost fertility. Palm leaves showed anti-hyperglycemic effects via inhibition of α-amylase and α-glucosidase. Unlike previous studies, this study highlighted the functional roles of all the plant parts of the palm tree and provided insights into the various mechanism of action of their bioactive compounds. Although scientific shreds of evidence have been growing over the years, there is still a dearth of studies concerning the clinical validation of the date fruit and other plant parts to provide strong evidence on their medicinal uses. In conclusion, P. dactylifera can be regarded as a potent medicinal plant with prophylactic potential and should be further explored to alleviate the burden of both communicable and non-communicable diseases.
... Lignans are a class of diphenolic nonsteroidal phytoestrogens often found glycosylated in planta and are purported with a wide variety of health benefits (Dixon 2004;Thompson et al. 2006;Arroo et al. 2009;Prakash and Gupta 2011;. Flax seeds are a rich source of secoisolariciresinol diglucoside (SDG) lignans (Westcott and Muir 1996;Patel et al. 2012;Goyal et al. 2014;Fang et al. 2016). ...
Genomic selection (GS) or genomic prediction (GP) is a type of marker-assisted selection that relies on genome-wide markers to predict genomic-estimated breeding values (GEBVs) of phenotypes. GS is quickly becoming a conventional approach in both plant and animal breeding to increase selection accuracy, reduce breeding cost and shorten breeding cycles. The concept of GS models was first developed using genome-wide random markers, with marker density being a key element in estimating the predictive ability in breeding populations. It is currently straightforward to generate high-density marker datasets thanks to the remarkable advances in genotyping technologies. Recent studies showed that high-density genome-wide random markers do not necessarily generate high genomic predictive ability in GS because the vast majority of markers are unrelated to the traits of interest, thus generating background noises and lowering the predictive ability. Alternatively, the use of quantitative trait loci (QTLs), identified through genome-wide association study (GWAS) methods, in GS models can significantly improve genomic predictive ability and reduce the genotyping cost of the test populations. Here, we present recent findings, discuss a few case studies, a QTL-based GS strategy and a genomic cross-predictions for flax breeding improvement.
... Lignans are a class of diphenolic nonsteroidal phytoestrogens often found glycosylated in planta and are purported with a wide variety of health benefits (Dixon 2004;Thompson et al. 2006;Arroo et al. 2009;Prakash and Gupta 2011;. Flax seeds are a rich source of secoisolariciresinol diglucoside (SDG) lignans (Westcott and Muir 1996;Patel et al. 2012;Goyal et al. 2014;Fang et al. 2016). ...
Quantitative trait locus (QTL) mapping is a powerful statistical genetics approach to identify genomic regions and candidate genes associated with traits of interest in plants. Depending on the genetic populations and the theoretical considerations, either linkage map-based QTL mapping or linkage disequilibrium-based association mapping, commonly known as genome-wide association study (GWAS), is widely used QTL mapping strategies. Recently, several multi-locus statistical models have been developed and applied in crops, including flax, leading to the identification of large- and small-effect QTLs for complex traits. In the last decade, at least 21 QTL mapping studies were reported in flax. Using bi-parental populations or germplasm collections, more than 1000 unique QTLs or quantitative trait nucleotides (QTNs) have been reported for 37 traits, including seed yield and agronomic traits, fiber yield and quality, seed quality, and abiotic and biotic traits. Some candidate genes neighboring these QTLs/QTNs have also been identified. These results provide a large set of genomic resources and genomic tools for genomics-assisted breeding, such as marker-based selection and genomic selection to pyramid favorable alleles into cultivars.
Sesame, the “queen of oilseeds,” is highly valued for its edible oil, though it contributes very small proportion to the world’s vegetable oil production. Oil content in sesame seeds is close to 50% and protein to 25% of the seed weight. A variety of extraction methods are used to obtain oil from sesame seeds. Among them, mechanical cold press extraction method is highly preferred for oil extraction, as it yields improved oil quality without affecting oil expelling conditions. However, the oil recovery is comparatively lower (~65%) than the chemical methods of oil extraction. Chemical methods are preferred for oil extraction due to higher oil recovery; however, the chemical solvents used had a deleterious impact on the human health and environment which pushed the development of innovative, ecofriendly oil extraction techniques. These advanced techniques employ aqueous extraction, pressurized fluids, phase-partitioning, enzyme-assisted aqueous extraction, etc., which offers numerous advantages such as high extraction yields and quality in short period with minimized solvent utilization. The fatty acid composition of sesame oil depicts that it is high in oleic (40–41%) and linoleic acid (41–43%), which makes it highly nutritive. Also, sesame oil is rich in native antioxidants, viz., lignans (sesamin, sesamolin, sesamol), tocopherols, phytosterols, etc. This chapter also compares the nutritional quality of sesame oil and other vegetable oils. In addition to better oil extraction techniques, there is pressing need to develop efficient techniques for assessing the quality of the extracted oil in order to detect any food fraud committed by mixing low-priced edible oils with high-value oil. Although techniques used in past were reliable, majority of them were destructive assays, hence there is need for improvement in non-destructive methodologies. A range of non-destructive methods that are fast, accurate, and reliable have been devised, which include NIR spectroscopy, FTIR spectroscopy, Raman spectroscopy, hyperspectral imaging (HIS), E-noses, etc. These non-destructive methods can nowadays be implemented through portable analyzers. The information compiled in this chapter may assist oilseed researchers and processors in selecting appropriate method for extracting sesame oil and for assessing its quality.
Introduction:
Overactive bladder (OAB) is a prevalent disorder with a significant impact on quality of life. The pathophysiology of OAB is multifactorial and the majority of patients will require treatment with multiple therapies across the course of their disease. First-line treatments include bladder retraining, fluid advice and pelvic floor muscle training. Following this, patients may be offered treatment with anticholinergic and β3 agonist medications. Anticholinergics are known to have high rates of discontinuation due to side effects and there are concerns regarding anticholinergic load and its impact on cognitive function in older adults.
Areas covered:
This paper aims to discuss the current and emerging treatment options available for patients who suffer from OAB.
Expert opinion:
The management of OAB in the clinical setting remains challenging. The goal of newer pharmacotherapies in OAB would be treatment that provides long-term symptomatic relief with minimal side effects and an improved quality of life. The future of OAB research is promising and should consider the implications of the gut-bladder axis, regenerative medicine, biomarkers and the role of digital health.
Introduction/Objectives
Premenstrual syndrome (PMS) is the group of symptoms that occur before menses and remit after that. The pathophysiology of PMS is related to hormonal disturbances. Date palm fruit (Phoenix dactylifera L.) has many functional properties that are beneficial for women's health. This study aimed to investigate the effect of feeding dates on PMS symptoms.
Method
The fruit was fed conveniently to 36 volunteers, 16 and 20 in the control and dates groups, respectively. To monitor PM symptoms, a questionnaire was developed, validated, and tested for reliability.
Results
Results of this research yielded a valid (KMO, Barlett factor, and ꭕ2 test values of 0.541, <0.001, and 0.105 respectively) reliable (Cronbach’s-α value= 0.761) questionnaire. Feeding dates caused earlier onset of mood changes (0.017*), heavy bleeding (0.012*), and bleeding clots (0.025*). The onset of mood changes correlated significantly (P=0.048*) and negatively (r2= - 0.347) with luteinizing hormone. Additionally, prolactin was correlated significantly and negatively with the onset of abdominal cramps. Within the same line, progesterone was correlated negatively with vaginal secretions (r2= - 0.389, P=0.016*). On the other hand, breast tenderness was correlated (r2=0.391) significantly (P=0.022*) with 17-β-estradiol.
Conclusion
This study showed an ameliorating effect of dates on some PMS symptoms, i.e., abdominal cramps, mood changes, heavy bleeding, vaginal secretions, and bleeding clots.
We have been indoctrinated into believing truths founded in tainted research and flawed opinions. These lies have, impart, caused America's obesity rate to surpass 40% of adults. While eating healthy is a part of a healthy lifestyle and beneficial for physical health, it is not the full scope of the awareness we should be equipped with. Items we eat out of, touch, wear, and breathe all contribute to a hormonal epidemic. In men, testosterone is rapidly decreasing causing all kinds of reproductive, physical, and mental issues. Testosterone being the building block of a man, it is no wonder modern men are suffering an abundance of issues that were previously unheard of. Synthetic materials bringing strength, durability, and elasticity were intended for the benefit of society, but it seems they have been the downfall. Instead of properly researching this new magic material it has been coined as the new steel, and more than that. These plastics are being used in our packaging for both food and drink, as well as being used as the core for clothes, hygiene products, shoes, and glasses; practically everything we use has some sort of plastic element within it.
The lignan secoisolariciresinol (SECO) diglucoside (SDG) is a phytoestrogen with diverse effects. LuUGT74S1 glucosylates SECO to SDG, whereby only small amounts of the monoglucoside SMG are formed intermediately, which exhibit increased activity. To identify critical amino acids that are important for enzymatic activity and the SMG/SDG ratio, 3D structural modeling and docking, as well as site-directed mutation studies, were performed. Enzyme assays with ten mutants revealed that four of them had identical kinetic data to LuUGT74S1, while three showed reduced and one increased catalytic efficiency kcat/Km. S82F and E189L substitutions resulted in the complete absence of activity. A17 and Q136 are crucial for the conversion of SMG to SDG as A17S and Q136F mutants exhibited the highest SMG/SDG ratios of 0.7 and 0.4. Kinetic analyses show that diglucosylation is an essentially irreversible reaction, while monoglycosylation is kinetically favored. The results lay the foundation for the biotechnological production of SMG.
Cereals are the basis of much of the world’s daily diet. Recently, there has been considerable interest in the beneficial properties of wholegrains due to their content of phytochemicals, particularly polyphenols. Despite this, the existing data on polyphenolic composition of cereal-based foods reported in the most comprehensive databases are still not updated. Many cereal-based foods and phenolic compounds are missing, including pigmented ones. Observational epidemiological studies reporting the intake of polyphenols from cereals are limited and inconsistent, although experimental studies suggest a protective role for dietary polyphenols against cardiovascular disease, diabetes, and cancer. Estimating polyphenol intake is complex because of the large number of compounds present in foods and the many factors that affect their levels, such as plant variety, harvest season, food processing and cooking, making it difficult matching consumption data with data on food composition. Further, it should be taken into account that food composition tables and consumed foods are categorized in different ways. The present work provides an overview of the available data on polyphenols content reported in several existing databases, in terms of presence, missing and no data, and discusses the strengths and weaknesses of methods for assessing cereal polyphenol consumption. Furthermore, this review suggests a greater need for the inclusion of most up-to-date cereal food composition data and for the harmonization of standardized procedures in collecting cereal-based food data and adequate assessment tools for dietary intake.
The enterolignans, enterolactone and enterodiol, the main metabolites produced from plant lignans by the gut microbiota, have enhanced bioavailability and activity compared to their precursors, with beneficial effects on metabolic and cardiovascular health. Although extensively studied, the biosynthesis, cardiometabolic effects, and other therapeutic implications of mammalian lignans are still incompletely understood. The aim of this review is to provide a comprehensive overview of these phytoestrogen metabolites based on up-to-date information reported in studies from a wide range of disciplines. Established and novel synthetic strategies are described, as are the various lignan precursors, their dietary sources, and a proposed metabolic pathway for their conversion to enterolignans. The methodologies used for enterolignan analysis and the available data on pharmacokinetics and bioavailability are summarized and their cardiometabolic bioactivity is explored in detail. The special focus given to research on the health benefits of microbial-derived lignan metabolites underscores the critical role of lignan-rich diets in promoting cardiovascular health.
With the recognition of the importance of the gut–brain axis in Parkinson’s disease (PD) etiology, there is increased interest in developing therapeutic strategies that target α-synuclein, the hallmark abhorrent protein of PD pathogenesis, which may originate in the gut. Research has demonstrated that inhibiting the aggregation, oligomerization, and fibrillation of α-synuclein are key strategies for disease modification. Polyphenols, which are rich in fruits and vegetables, are drawing attention for their potential role in this context. In this paper, we reviewed how polyphenols influence the composition and functional capabilities of the gut microbiota and how the resulting microbial metabolites of polyphenols may potentially enhance the modulation of α-synuclein aggregation. Understanding the interaction between polyphenols and gut microbiota and identifying which specific microbes may enhance the efficacy of polyphenols is crucial for developing therapeutic strategies and precision nutrition based on the microbiome.
Lignans are phytoestrogens found in various forms such as glycosides, ester-linked oligomers, and aglycones in a variety of foods, including soy products, legumes, grains, nuts, vegetables, and fruits. This study aimed to optimize the extraction of lignans from cereal grains using response surface methodology (RSM). Lignans, including secoisolariciresinol (Seco), matairesinol (Mat), pinoresinol (Pin), lariciresinol (Lar), and syringaresinol (Syr), were quantified using high-performance liquid chromatography–tandem mass spectrometry. A Box–Behnken design was employed to determine the optimal values for three extraction parameters: temperature (X1: 20°C–60°C), methanol concentration (X2: 60%–100%), and extraction time (X3: 30–90 min). The highest lignan contents were obtained at X1 = 44.24°C, X2 = 84.64%, and X3 = 53.63 min. To apply these experimental conditions to the actual experiment, the optimal conditions were slightly adjusted to X1 = 40°C, X2 = 80%, and X3 = 60 min. The predicted results closely matched the experimental results obtained using the modified optimal extraction conditions. The highest lignan content found in barley sprouts (85.930 μg/100 g), however, most grains exhibited relatively low concentrations of lignans. These findings provide valuable insights into the lignan content of grains and contribute to the generation of reliable data in this field.
Lignans are biologically active compounds widely distributed, recognized, and identified in seeds, fruits, and vegetables. Lignans have several intriguing bioactivities, including anti-inflammatory, antioxidant, and anticancer activities. Nrf2 controls the expression of many cytoprotective genes. Activation of Nrf2 is a promising therapeutic approach for treating and preventing diseases resulting from oxidative injury and inflammation. Lignans have been demonstrated to stimulate Nrf2 signaling in a variety of in vitro and experimental animal models. The review summarizes the findings of fourteen lignans (Schisandrin A, Schisandrin B, Schisandrian C, Magnolol, Honokiol, Sesamin, Sesamol, Sauchinone, Pinoresinol, Phyllanthin, Nectandrin B, Isoeucommin A, Arctigenin, Lariciresinol) as antioxidative and anti-inflammatory agents, affirming how Nrf2 activation affects their pharmacological effects. Therefore, lignans may offer therapeutic candidates for the treatment and prevention of various diseases and may contribute to the development of effective Nrf2 modulators.
Introduction This study aims to investigate the relationship between phytoestrogens and endometriosis development. Endometriosis results from uterine-like endometrial and stromal cells growing outside the uterus. People with endometriosis typically experience chronic inflammation, pelvic pain, and infertility resulting in lowered quality of life. Due to their structural similarities, phytoestrogens present in diets possess the ability to mimic the activity of estrogen and influencae endometriosis development. Method To better understand the role phytoestrogen plays in the development of endometriosis, a prospective clinical cohort study is proposed. The study will be conducted with a sample population of 196 participants lasting for six years. Participants will be recruited if they are present with endometriosis on ultrasound and are confirmed through laparoscopy. Participants will be provided with a questionnaire describing the amount of phytoestrogen-containing food in their diets. This data will be compared against Agriculture-Agri-Food Canada to determine the relative concentration/amount of phytoestrogen in participants' diet foods. The participants will be divided into groups, with the exposed group being provided with recommendations on high phytoestrogen-based foods to incorporate into their daily diet and the unexposed group foods to avoid. Participants’ diets will be analyzed every six months and lesion location, size and phenotype will be assessed via ultrasound. Analysis of variance will be used to determine lesion size, location and phenotypes, paired t-test to determine inflammatory marker protein concentration and p-test to dictate statically significant results. Anticipated Results It is expected that participants with high amounts of phytoestrogen-containing foods in their diet will present a continual development of endometrial lesions while unexposed participants will present a decrease in endometrial lesion development. Conclusion Based on the expected results, dietary phytoestrogen may lead to the development of endometriosis. As a result, women and dietitians should consider the effect of phytoestrogen-based foods when preparing diets. Future research should be conducted to assess phytoestrogen-containing foods to reap the nutritional benefits of these foods but also minimize endometrial lesions growth.
Endocrine disruption is a relatively new field of study, as endocrine disruptors were not formally acknowledged by regulatory agencies until 1996. Over the years, many federal and international regulatory agencies and professional associations have provided varying terminology and classifications; however, in general, exposure to endocrine disruptors, or endocrine‐disrupting chemicals (EDCs), at environmentally relevant doses results in adverse effects consequent to interfering with endocrine function. Apart from minor nomenclature disagreements, there are challenges and limitations to this field, as EDC classification criteria can vary substantially in considering evidence for a biologically plausible causal relationship between the endocrine activity and the induced adverse effect. Accordingly, international consensus for unambiguous designation of EDCs is lacking. Therefore, this chapter will not attempt to resoundingly identify all known or suspected EDCs; rather, the objective of this chapter is to first provide historical context to chemical regulation, including on endocrine disruption and its development as a field, and then follow with a review of the health implications, which highlights some fundamental concepts of endocrine disruption and incorporates a tale of the infamous public health disaster resulting from prescribing pregnant women diethylstilbestrol (DES), a potent synthetic estrogen. The current testing guidelines and standards for EDCs are also reviewed, demonstrating the restricted focus on canonical endocrine disruption that is characterized by nuclear hormone receptor‐based activity and the estrogenic, androgenic, thyroidal, and steroidogenic (EATS) modalities. To end, some of the more recently regulated EDCs, particularly bisphenol A and phthalates, as well as other ubiquitous EDCs, like phytoestrogens and flame retardants, are reviewed.
Significance: In recent decades, male fertility has been severely reduced worldwide. The causes underlying this decline are multifactorial and include, among others, genetic alterations, changes in the microbiome, and the impact of environmental pollutants. Such factors have in common that they can dysregulate physiological levels of reactive species of oxygen (ROS) and nitrogen (RNS) in the patient, generating oxidative and nitrosative stress that impairs fertility. Recent Advances: Recent studies have delved into other factors involved in the dysregulation of ROS and RNS levels, such as diet, obesity, persistent infections, environmental pollutants and gut microbiota, thus leading to new strategies to solve male fertility problems, such as consuming prebiotics to regulate gut flora or treating psychological conditions. Critical Issues: The pathways where ROS or RNS may be involved as modulators are still under investigation. Moreover, the extent to which treatments can rescue male infertility as well as whether they may have side effects remain, in most cases, to be elucidated. For example, it is known that prescription of antioxidants to treat nitrosative stress can alter sperm chromatin condensation, which makes DNA more exposed to ROS and RNS, and may thus affect fertilization and early embryo development. Future Directions: The involvement of extracellular vesicles, which might play a crucial role in cell communication during spermatogenesis and epididymal maturation, and the relevance of other factors like sperm epigenetic signatures should be envisaged in the future.
Neurological disorders are possibly the most prevalent and have been identified to occur among individuals with autism beyond chance. These disorders encompass a diverse range of consequences with neurological causes and have been regarded as a major threat to public mental health. There is no tried-and-true approach for completely protecting the nervous system. Therefore, plant-derived compounds have developed significantly nowadays. Coumestrol (CML) is a potent isoflavone phytoestrogen with a protective effect against neurological dysfunction and has been discovered to be structurally and functionally similar to estrogen. In recent years, more research has been undertaken on phytoestrogens. This research demonstrates the biological complexity of phytoestrogens, which consist of multiple chemical families and function in various ways. This review aimed to explore recent findings on the most significant pharmacological advantages of CML by emphasising neurological benefits. Numerous CML extraction strategies and their pharmacological effects on various neurological disorders, including PD, AD, HD, anxiety, and cognitive impairments, were also documented.
Scope
Lignans are a group of phenolic compounds commonly found in plants, often in the form of glycosides. This study investigates the differences in the digestion, absorption, and metabolism of lignans and their glucosides using pinoresinol (PIN) and pinoresinol-4-O-β-D-glucopyranoside (PMG).
Methods and results
After oral administration mice PIN and PMG with a dose of 0.1 µmol kg−1. The results showed that the stomach and small intestine rapidly absorbe PIN and PMG in their prototype form. After oral administration of 0.25 h, serum levels of PIN and PMG reach peak values of 61.14 and 52.97 ng mL−1, respectively. This indicates a faster PIN absorption rate than PMG, likely due to the glycosides attach to the parent compound, with concentrations of 1574.14 and 876.75 ng g−1, respectively. Pharmacokinetic analysis reveals that PIN has a greater area under the curve and a longer half-life than PMG in serum and liver. Moreover, mice in the PIN group exhibit higher metabolite levels in the serum and liver compared to those in the PMG group.
Conclusion
The deglycosylation process that occurs during the pickling of white radish facilitates the absorption and metabolism of the lignans fraction in the body.
Gastrointestinal cancer is one of the most prevalent causes of cancer-related deaths in the world. Recent research demonstrates that phytochemicals are critical in preventing and managing gastrointestinal cancer. The increased intake of phytochemicals could reduce the risk of cancer by inhibiting cancer cell proliferation, inducing apoptosis and autophagy, and suppressing angiogenesis as well as cancer cell metastasis. These mechanisms are also known to counter Helicobacter pylori infection and modulate gut microbiota. There is preliminary data suggesting that daily supplementation with high doses of certain vitamins combined with conventional therapeutic agents may enhance their growth inhibitory effects on tumor cells and protect normal tissues against some of their toxic effects. This book attempts to fill gaps on the role of phytonutrients in the treatment of cancer in the gastrointestinal tract (GIT). It discusses the action of individual vitamins on cellular and molecular parameters and describes how vitamins inhibit protein kinase C activity, increase the production of certain growth factors, and modulate the expression of a number of oncogenes. The book is divided into 2 parts. The first part summarizes the pathophysiology of GIT cancers and introduces readers to anticancer phytonutrients. A chapter on the status of FDA approved nutraceuticals rounds up this section. The second part of the book provides a systematic review on the different plant derived chemicals that can be used to treat GIT cancer. Each chapter in this section focuses on a specific type of phytochemical agent and its molecular mechanisms relevant to the disease. This book will give the reader a holistic view of gastrointestinal cancer treatment and the value of natural compounds in developing functional food and drugs for preventive medicine.
Over the last decades, global concerns regarding possible adverse health effects of chemical pollutants on the hormonal systems of living organisms in wildlife and humans are constantly growing. Endocrine-active and endocrine-disrupting chemicals (EDC) belong to a heterogeneous class of exogenous chemicals, including various persistent anthropogenic contaminants, pesticides, distinct substances used in consumer products, and also natural compounds. Exposure through the food chain is considered essential for most EDC, while they may enter the food chain as residues from animal- or plant-based food production (e.g. pesticides or pharmaceutical residues), may be released from food contact materials, may be present due to natural contamination (e.g. mycoestrogens), may enter via a polluted environment and also as natural plant food ingredients (e.g. phytoestrogens). The complexity of the subject is due to: a) the ubiquitous occurrence and hardly possible avoidance of many substances with supposed endocrine properties, b) the scientific disagreement among experts and the huge number of partly controversial study outcomes and c) the increasing pressure of the public, necessitating a higher level of transparency and clear-cut orientation with respect to avoidance and reduction strategies.In this light, the current review intends to provide an overview of the historical and regulatory developments regarding the topic of EDC, discusses the important difference between endocrine-active and disruptive substances and presents some key characteristics of endocrine acting substances for a better understanding of their relevance for the food chain including possible long-term effects, windows of sensitivity, low-dose and possible “cocktail” effects. In addition, a comprehensive overview on the different exposure paths of endocrine-active and disruptive substances in the food chain is given, with both a focus on naturally occurring food ingredients and possible contaminations from external sources.
Flax (Linum usitatissimum L.) is grown for its linseed and baste fibres and is used for industrial, feed, food, and nutraceutical applications. Flax lipids, including structural and storage lipids, proteins, starch, and seed mucilage and lignans are the key components for flax’s industrial and health applications. Although extensive literature is available on each component or a combination of these metabolites, no systematic review has yet addressed them all in the same study, nor exists an update on the methods and tools used for generating their metabolite profiles. The carbon and metabolic flux between pathways leading to the production and regulation of these metabolites in planta is still also elusive. A thorough understanding of the factors leading to optimal production of these metabolites in flax and the interlinked metabolic flows between pathways is paramount to the development of strategies aimed at tailoring the next generation of flax’s metabolome that meets the emerging societal needs. This chapter will review and discuss the current knowledge of flax lipids, proteins, starch, and seed lignans. The analytical tools used to determine the metabolite and transcriptomic profiles and content in flax, as well as the current knowledge on the genetic control, regulation biosynthesis, and interplay between metabolic pathways, will be discussed.
The metabolism of the plant lignans matairesinol, secoisolariciresinol, pinoresinol, syringaresinol, arctigenin, 7-hydroxymatairesinol, isolariciresinol, and lariciresinol by human fecal microflora was investigated to study their properties as mammalian lignan precursors. The quantitative analyses of lignan precursors and the mammalian lignans enterolactone and enterodiol were performed by HPLC with coulometric electrode array detector. The metabolic products, including mammalian lignans, were characterized as trimethylsilyl derivatives by gas chromatography−mass spectrometry. Matairesinol, secoisolariciresinol, lariciresinol, and pinoresinol were converted to mammalian lignans only. Several metabolites were isolated and tentatively identified as for syringaresinol and arctigenin in addition to the mammalian lignans. Metabolites of 7-hydroxymatairesinol were characterized as enterolactone and 7-hydroxyenterolactone by comparison with authentic reference compounds. A metabolic scheme describing the conversion of the most abundant new mammalian lignan precursors, pinoresinol and lariciresinol, is presented. Keywords: Phytoestrogens; lignans; matairesinol; secoisolariciresinol; lariciresinol; pinoresinol; syringaresinol; isolariciresinol; arctigenin; 7-hydroxymatairesinol; mammalian lignans; enterolactone; enterodiol
Phytoestrogens are natural plant substances. The three main classes are isoflavones, coumestans, and lignans. Phytoestrogens have anticarcinogenic potential, but they have also significant estrogenic properties. For an evalu-ation of the effect of phytoestrogens on breast cancer risk we reviewed the analytical epidemiological data. A total of 18 studies were included [1–18]. Up to now, there are 13 studies that have assessed the direct relation between the individual dietary intake of soy products and the risk of breast cancer [1–13]. Overall, results do not show protective effects, with the exception maybe for women who consume phytoestrogens at adolescence or at very high doses [5, 7, 8]. Only four of these 13 studies are prospective, and none of them found statistically significant breast cancer reductions. Four studies assessed urinary isoflavones excretion in relation to breast cancer [14–17]. Three of these are case control studies [14–16], where excretion was measured after breast cancer occurrence and thus seriously limiting causal interpretation of the results. The only prospective study with urinary measurements before breast cancer occurrence was done in a Dutch postmenopausal population and showed a non-significant breast cancer risk reduction for high excretion [17]. Three studies measured enterolactone (lignan): two case control studies reported a preventive effect on breast cancer risk [14, 18], but the only prospective study did not [17]. In conclusion, few prospective studies (n = 5) were done to assess the effects of phytoestrogens on breast cancer risk. None of them found protective effects. However, these prospective studies did not focus on 'age at consumption', which seems to be important based on results from dietary case control studies done so far.
Tea is a beverage consumed widely throughout the world. The existence in tea of chemopreventing compounds possessing antimutagenic, anticarcinogenic and antioxidative properties has been reported. High intakes of tea and foods containing flavonoids have recently been shown to be negatively correlated to the occurrence of CHD. However, tea may contain other compounds with similar activities. Using a new gas chromatographic-mass spectrometric method we measured lignans and isoflavonoids in samples of twenty commercial teas (black, green and red varieties) and, for comparison, six coffees. Both unbrewed and brewed tea were investigated. The analysis of the teas yielded relatively high levels of the lignans secoisolariciresinol (5.6-28.9 mg/kg; 15.9-81.9 mumol/kg) and matairesinol (0.56-4.13 mg/kg; 1.6-11.5 mumol/kg) but only low levels of isoflavonoids. Because the plant lignans, as well as their mammalian metabolites enterolactone and enterodiol, have antioxidative properties and these mammalian lignans occur in high concentrations in plasma, we hypothesize that lignan polyphenols may contribute to the protective effect of tea on CHD.
TABLE 3 Compilation of Characteristic Estrogenic and Antiestrogenic Activities a of the Tested Phytoestrogens Compared to DES and E2 Ligand ERa ERb DES, E2 Full potent b agonist ZEA Mixed potent agonist/antagonist Mixed agonist/antagonist COUM Full agonist GEN Full, weak agonist Full agonist Equol Full, very weak agonist Full, weak agonist RESV Mixed weak agonist/antagonist ENL, 6OH-ENL Partial agonist/antagonist 347-IF, 674-IF Full very weak superagonist a Compilation of (anti)-estrogenic activities are based on data of ligand binding to ERa/ERb and transactivation or inhibition of ERa/ERb presented here. b Potent means more than 10% potency compared to DES; agonist means less than 10% but more than 1% potency compared to DES; weak means less than 1% but more than 0.1% potency compared to DES; very weak means less than 0.1% potency compared to DES.
Consumption of a plant-based diet can prevent the development and progression of chronic diseases that are associated with extensive neovascularization. To determine whether prevention might be associated with dietary derived angiogenesis inhibitors, we have fractionated urine of healthy human subjects consuming a plant-based diet and examined the fractions for their abilities to inhibit the proliferation of vascular endothelial cells. One of the most potent fractions contained several isoflavonoids, which we identified by gas chromatography-mass spectrometry and subsequently synthesized. Of all synthetic compounds, the isoflavonoid genistein was the most potent and inhibited endothelial cell proliferation and in vitro angiogenesis at half maximal concentrations of 5 and 150 mumol/L, respectively. Moreover, genistein inhibited the proliferation of various tumor cells. Genistein excretion in urine of subjects consuming a plant-based diet is in the micromolar range, which is 30-fold higher than that of subjects consuming a traditional Western diet. The high concentrations of genistein in urine of vegetarians and our present results suggest that genistein may contribute to the preventive effect of plant-based diet on chronic diseases, including solid tumors, by inhibiting neovascularization and tumor cell proliferation. Thus genistein may have important applications in the treatment of solid tumors and angiogenic diseases.
Breast cancer rates among Asian-Americans are lower than those of US whites but considerably higher than rates prevailing in Asia. It is suspected that migration to the US brings about a change in endocrine function among Asian women, although reasons for this change remain obscure. The high intake of soy in Asia and its reduced intake among Asian-Americans has been suggested to partly explain the increase of breast cancer rates in Asian-Americans. We conducted a population-based case-control study of breast cancer among Chinese-, Japanese-, and Filipino-American women in Los Angeles County MSA, San Francisco Oakland MSA, and Oahu, Hawaii. Using a common questionnaire which assessed frequency of intake of some 90 food items, 597 Asian-American women (70% of those eligible) diagnosed with incident, primary breast cancer during 1983-1987 and 966 population-based controls (75% of those eligible) were interviewed. Controls were matched to cases on age, ethnicity, and area of residence. This analysis compares usual adult intake of soy (estimated primarily from tofu intake) among breast cancer cases and control women. After adjustment for age, ethnicity and study area, intake of tofu was more than twice as high among Asian-American women born in Asia (62 times per year) compared to those born in the US (30 times per year). Among migrants, intake of tofu decreased with years of residence in the US. Risk of breast cancer decreased with increasing frequency of intake of tofu after adjustment for age, study area, ethnicity, and migration history; the adjusted OR associated with each additional serving per week was 0.85 (95% CI = 0.74-0.99). The protective effect of high tofu intake was observed in pre- and postmenopausal women. This association remained after adjustment for selected dietary factors and menstrual and reproductive factors. However, this study was not designed specifically to investigate the role of soy intake and our assessment of soy intake may be incomplete. We cannot discount the possibility that soy intake is a marker of other protective aspects of Asian diet and/or Asian lifestyle.
The association between soya foods and breast cancer risk was investigated in a prospective study of 34759 women in Hiroshima and Nagasaki, Japan. Women completed dietary questionnaires in 1969-1970 and/or in 1979-1981 and were followed for incident breast cancer until 1993. The analysis involved 427 cases of primary breast cancer in 488989 person-years of observation. The risk for breast cancer was not significantly associated with consumption of soya foods: for tofu, relative risks adjusted for attained age, calendar period, city, age at time of bombings and radiation dose to the breast were 0.99 (95% CI 0.80-1.24) for consumption two to four times per week and 1.07 (0.78-1.47) for consumption five or more times per week, relative to consumption once a week or less; for miso soup, relative risks were 1.03 (0.81-1.31) for consumption two to four times per week and 0.87 (0.68-1.12) for consumption five or more times per week, relative to consumption once a week or less. These results were not materially altered by further adjustments for reproductive variables and were similar in women diagnosed before age 50 and at ages 50 and above. Among 17 other foods and drinks examined only dried fish (decrease in relative risk with increasing consumption) and pickled vegetables (higher relative risk with higher consumption) were significantly related to breast cancer risk; these associations were not prior hypotheses and, because of the large number of comparisons made, they may be due to chance.
Dietary isoflavone and lignan phytoestrogens are potential chemopreventive agents. This has led to a need to monitor exposure to these compounds in human populations and to determine which components of a mixed diet contribute to the exposure. Typically, urinary isoflavonoid excretion is associated with soy consumption and that of lignans is associated with whole grains. However, other plant foods are known to contain phytoestrogen precursors. The purpose of this study was to examine the association between urinary isoflavonoid and lignan excretion and intakes of vegetables and fruits (V&F). Isoflavonoids (genistein, daidzein, O-desmethylangolensin, and equol) and lignans (enterolactone, enterodiol, and matairesinol) were measured in urine collected for 3 days from 49 male and 49 female volunteers (age, 18-37 years) reporting a wide range of habitual V&F intakes. Dietary intakes were assessed using 5-day diet records and a food frequency questionnaire. V&F groupings (total V&F, total V, total F, soyfoods, and V&F grouped by botanical families) were used to assess the relationship between V&F intake and urinary isoflavonoid and lignan excretion. Pearson correlations were performed. Intake of soyfoods was correlated significantly with urinary genistein (r = 0.40; P = 0.0001), O-desmethylangolensin (r = 0.37; P = 0.0002), daidzein (r = 034; P = 0.0007), and the sum of isoflavonoids (r = 0.39; P = 0.0001). There was no association between equol excretion and soy intake or between the isoflavonoids and any other V&F groupings. In addition, isoflavonoid excretion was correlated positively with intake of high-fat and processed meats, particularly among men who did not consume soy. This suggests that, even in the United States, on a Western diet, soyfoods are the primary contributors to isoflavone intake; however, additional "hidden sources" of soy may also contribute to exposure. In contrast, a variety of fiber-containing foods contributed to lignan excretion; the sum of the urinary lignans, enterodiol, enterolactone, and matairesinol, was associated with intake of total F (r = 0.27; P = 0.008), total V&F (r = 0.25; P = 0.01), soyfoods (r = 0.28; P = 0.006), and dietary fiber (r = 0.36; P = 0.0003). Overall, urinary phytoestrogens (isoflavonoids + lignans) were significantly higher in "high" compared with "low" V&F consumers. Compared with the "low" V&F group, the "high" group consumed diets that were, on average, higher in fiber and carbohydrate and soyfoods and lower in fat; thus, the urinary phytoestrogens may also be a useful marker of healthier dietary patterns.
The potential for the extraction of the plant lignan hydroxymatairesinol (HMR) in large scale from Norway spruce (Picea abies) has given us the opportunity to study the metabolism and biological actions of HMR in animals. HMR, the most abundant single component of spruce lignans, was metabolized to enterolactone (ENL) as the major metabolite in rats after oral administration. The amounts of urinary ENL increased with the dose of HMR (from 3 to 50 mg/kg), and only minor amounts of unmetabolized HMR isomers and other lignans were found in urine. HMR (15 mg/kg body wt po) given for 51 days decreased the number of growing tumors and increased the proportion of regressing and stabilized tumors in the rat dimethylbenz[a]anthracene-induced mammary tumor model. HMR (50 mg/kg body wt) did not exert estrogenic or antiestrogenic activity in the uterine growth test in immature rats. HMR also showed no antiandrogenic responses in the growth of accessory sex glands in adult male rats. Neither ENL nor enterodiol showed estrogenic or antiestrogenic activity via a classical alpha- or beta-type estrogen receptor-mediated pathway in vitro at < 1.0 microM. HMR was an effective antioxidant in vitro.
We evaluated the association of soyfood intake and breast cancer risk in a population-based case-control study among Chinese women in Shanghai. Included in the study were 1459 cases and 1556 age-matched controls, with respective response rates of 91.1% and 90.3%. Usual soyfood intake was assessed using a food frequency questionnaire (FFQ). Separate analyses were performed for all subjects and for the subset who reported no recent change in soyfood intake. The intake levels of soyfoods among women in Shanghai are high, with 96.6% women reporting soyfood consumption at least once a week. A statistically non-significant reduced risk (odds ratio (OR) = 0.78 95% CI = 0.52-1.16) of breast cancer was observed among those who reported eating soyfood at least once a week. Compared to those in the lowest decile intake group, women in the highest decile intake group had a 30% reduced risk of breast cancer (OR = 0.66, 95% CI = 0.46-0.95), but no monotonic dose-response relation was observed (P for trend, 0.28). Stratified analyses showed that the inverse association was restricted primarily among women who had a high body mass index (BMI), with an adjusted OR of 0.30 (95% CI = 0.10-0.94) observed for the highest intake group. The reduction in risk was stronger for breast cancer positive for both oestrogen receptor (ER) and progesterone receptor (PR) (OR = 0.44, 95% CI = 0.25-0.78) than those with other ER/PR status. More pronounced inverse associations were observed in analyses among those who reported no recent change in soyfood intake than those conducted in all subjects. A dose-response relation between soyfood intake and breast cancer risk was observed in this subset of women (P for trend, 0.02), with an OR of 0.46 (95%CI = 0.28-0.75) for those in the highest decile intake group. No clear monotonic dose-response relation was found between soyfood intake and breast cancer risk among regular soy eaters, but nevertheless the results suggest that regular soyfood consumption may reduce the risk of breast cancer, particularly for those positive for ER and PR; the effect may be modified by body mass index.
Wines have been studied a lot and several different groups of phenolic compounds have been analysed in wine samples, but lignans in wines have been only preliminary studied. In this study, we analysed 10 different wines of which eight were red wines and two white wines. Samples were selected among the most consumed wines in Finland in year 1999. Eight different lignans were analysed with HPLC using coulometric electrode array detector. The amount of lignans in red wines ranged from 0.812 to 1.406 mg/l. The main lignan in all studied wines was isolariciresinol and percentage amount of mammalian lignan precursors varied from 34 to 43% in the red wines. The amount of lignans was much lower in the studied white wines compared with the red wines.
The plant lignans, secoisolariciresinol (SEC) and matairesinol (MAT) are converted to the metabolites, enterodiol (ED) and enterolactone (EL), known as the mammalian lignans in the gastrointestinal tract. In vitro, mammalian lignans may have both estrogenic and antiestrogenic properties. Increased consumption of lignan-rich foods through the addition of brans, oilseeds and cereals in bread, muffins, health bars and breakfast cereal or emphasis on fruits and vegetables in a balanced diet has lead to the need for reliable data on lignan content in foods. The quantitative determination of the lignans to date by a direct method has involved hydrolysis of the glycoside and analysis of the resulting aglycones (SEC and MAT). The in vitro fermentation methodology, which simulates colonic fermentation with fecal microflora, has been utilized in the indirect analysis of foods where ED and EL are measured as an indication of the plant lignans. A compilation of the available data on the lignan content of various food groups and the assessment of these data by contrasting two different analytical methodologies are given. In general, in vitro fermentation gave higher values, compared to direct analysis, for most foods for which comparisons could be made.
We conducted a large-scale, hospital-based case-control study to evaluate differences and similarities in the risk factors of female breast cancer according to menopausal status. This study is based on a questionnaire survey on life style routinely obtained from outpatients who first visited the Aichi Cancer Center Hospital between January 1, 1988 and December 31, 1992. Among 36,944 outpatients, 1,186 women with breast cancer detected by histological examination were taken as the case group (607 premenopausal women and 445 postmenopausal women) and 23,163 women confirmed to be free of cancer were selected as the control group. New findings and reconfirmed factors of breast cancer were as follows. 1) The risk of at least one breast cancer history among subjects’ first-degree relatives was relatively high among pre- as well as post-menopausal women. 2) A protective effect of physical activity against breast cancer was observed among both pre- and post-menopausal women. 3) Dietary control decreased the risk of premenopausal breast cancer. 4) Current smoking and drinking elevated the risk of breast cancer in premenopausal women. 5) Decreasing trends of breast cancer risk were associated with intake of bean curd, green-yellow vegetables, potato or sweet potato, chicken and ham or sausage in premenopausal women, while in postmenopausal women a risk reduction was associated with a more frequent intake of boiled, broiled and/or raw fish (sashimi). Further study will be needed to clarify the age group- and/or birth cohort-specific risk factors for breast cancer among the young generation in Japan.
We investigated associations between diet and premenopausal bilateral breast cancer in a familial matched case-control study. We studied 140 cases from population-based registries in Los Angeles County (California) and Connecticut, and from the major hospitals in the southern parts of the Province of Quebec. Unaffected sisters of the cases served as matched controls (222 total). Dietary intake were assessed with a food frequency questionnaire. Total fat, monounsaturated fat, polyunsaturated fat, oleic acid, and linoleic acid intake was inversely associated with premenopausal bilateral breast cancer risk. Consumption of carbohydrates (and sweetened beverages) was associated with an increased risk. We observed no associations for dietary fiber, antioxidants, or major food groupings, but we did observe inverse associations for intake of low fat dairy products and tofu. These findings suggest that monounsaturated and polyunsaturated fats, as well as soy foods, might reduce the risk of premenopausal bilateral breast cancer.
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.
Mammalian lignans such as enterolactone and enterodiol, which are produced in the colon from precursors in foods, have been suggested as playing a role in the cancer-protective effect of vegetarian diets. Despite this, very little is known regarding the amount that is produced from different food products. Therefore, the objective of this study was to determine the production of mammalian lignans from 68 common plant foods by using the technique of in vitro fermentation with human fecal microbiota, which simulates colonic fermentation. Results showed a wide range (21-67,541 microgram(s)/100 g sample) in the amount of lignans produced. On the average as a group, the oilseeds produced the highest amounts (20,461 +/- 12,685), followed by the dried seaweeds (900 +/- 247), whole legumes (562 +/- 211), cereal brans (486 +/- 90), legume hulls (371 +/- 52), whole grain cereals (359 +/- 81), vegetables (144 +/- 23), and fruits (84 +/- 22). The vegetables produced the second highest concentration of lignans (1,546 +/- 280) when the data were expressed on a moisture-free basis. Flaxseed flour and its defatted meal were the highest producers of lignans (mean 60,110 +/- 7,431). Lignan production with the in vitro method related well to the urinary lignan excretion observed in rats and humans. The data should be useful in the estimation of lignan production from a given diet and in the formulation of high-lignan-producing diet for the purpose of reducing the cancer risk.
It is suspected that diet influences the risk of getting breast cancer. A study of diet and breast cancer was done among 200 Singapore Chinese women with histologically confirmed disease and 420 matched controls. A quantitative food-frequency questionnaire was used to assess intakes of selected nutrients and foods 1 year before interview. Daily intakes were computed and risk analysed after adjustment for concomitant risk factors. In premenopausal women, high intakes of animal proteins and red meat were associated with increased risk. Decreased risk was associated with high intakes of polyunsaturated fatty acids (PUFA), beta-carotene, soya proteins, total soya products, a high PUFA to saturated fatty acid ratio, and a high proportion of soya to total protein. In multiple analysis, the variables which were significant after adjustment for each other were red meat (p less than 0.001) as a predisposing factor, and PUFA (p = 0.02), beta-carotene (p = 0.003), and soya protein (p = 0.02) as protective factors. The analysis of dietary variables in postmenopausal women gave uniformly non-significant results. Our finding that soya products may protect against breast cancer in younger women is of interest since these foods are rich in phyto-oestrogens.
Lignans have, until recently, been found only in plants. Enterolactone and enterodiol are the major lignans present in the urine of humans and have a potential physiological protective role against cancer. It has been shown that these compounds can be formed in vitro by human faecal flora and that enterodiol is oxidized to enterolactone by bacteria that are present in stools at a concentration of up to 10(3)/g. It was also possible to produce both of these lignans in vitro from linseeds and from secoisolariciresinol, a precursor present in linseed, by bacteria present in stools, at a concentration of between 10(3) and 10(4)/g. Enterolactone was produced from matairesinol, a more abundant plant lignan than secoisolariciresinol, after incubation with a mixed faecal flora under both aerobic and anaerobic conditions. In each case conversion was dependent on the presence of viable bacteria. These findings indicate that a number of different pathways operate to produce enterolactone and enterodiol depending on the ingested dietary precursor.
In our laboratories, for several years, two phenolic compounds have been detected during gas chromatographic-mass spectrometric analysis of urinary steroid extracts from human and animal species. Although features of the mass spectra of their trimethylsilyl (TMS) ether derivatives resembled those of oestrogens, they were atypical of steroids. The possibility that they were artefacts of the isolation procedures was discounted after careful studies with blanks, by varying the extraction method and because they were present almost exclusively as conjugates of glucuronic acid. Several of the general characteristics of the unknown compounds were reported after one (referred to as compound 180/442) was found to have a cyclic pattern of excretion during the menstrual cycle of an adult vervet monkey (Fig. 1). An investigation of the nature and distribution of the compounds has shown them to be urinary constituents in humans, baboons, vervet monkeys and rats, and further related compounds have been detected, so far only in vervet monkey urine. We now report spectroscopic and chemical studies that show the two original compounds to be lignans, which have a 2,3-dibenzylbutane skeleton as their basic structure. Unlike all previously known natural lignans, invariably of plant origin, the two mammalian compounds carry phenolic hydroxy groups only in the meta position of the aromatic rings.
Lignans are a class of compounds with a dibenzylbutane skeleton which until recently had only been found in higher plants. The first lignans to be identified in humans and animals were trans 2,3-bis(3-hydroxybenzyl)-γ-butyrolactone (enterolactone and 2,3-bis(3-hydroxybenzyl) butane-1,4-diol (enterodiol). These structures differ from those of plant lignans by having aromatic rings substituted only in the meta position. Enterolactone and enterodiol are excreted in the urine and bile, predominantly as glucuronide conjugates, and intestinal microflora is required for their formation. It is not known, however, whether they are synthesized de novo by microrganisms or are formed from dietary precursors. We report here evidence that these mammalian lignans are formed by microbial action on precursor lignans which are present as dietary constituents of plant origin. Precursors are found in seeds of different species, being particularly abundant in linseed. From this source, 2,3-bis(3-methoxy-4-hydroxybenzyl) butane-1,4-diol (secoisolariciresinol) has been identified as a glycoside.
Isoflavonoid phytoestrogens and lignans in plants are known to be constituents of animal and human food and recently they have been found in human urine and other biological materials. These compounds have received increasing attention because of their interesting biological properties and possible role in human cancer and other diseases. The present study demonstrates that the main mammalian lignan enterolactone (trans-2,3-bis[(3-hydroxyphenyl)methyl]-butyrolactone) and some other diphenols are moderate or weak inhibitors of human estrogen synthetase (aromatase) and that this lignan binds to or near the substrate region of the active site of the P-450 enzyme. The inhibition is competitive with respect to testosterone and androstenedione, and the lignan affinity is 1/75-1/300 that of these natural substrates. It is suggested that the high concentration of lignans in vegetarians, by inhibiting aromatase in peripheral and/or cancer cells and lowering estrogen levels, may play a protective role as antipromotional compounds during growth of estrogen-dependent cancers.
We present a method for the quantitative determination of the phytoestrogens formononetin, biochanin A, daidzein, genistein, and coumestrol and simultaneously the lignans secoisolariciresinol (SECO) and matairesinol in plant-derived foods. These compounds are measured by isotope dilution gas chromatography-mass spectrometry in the selected ion monitoring mode (ID/GC/MS/SIM) using synthesized deuterated internal standards for the correction of losses during the procedure. A three-step hydrolysis--a rehydration with distilled H2O, followed by enzymatic and acid hydrolysis--has been applied in order to convert the diphenolic glycosides into their respective aglycones. Purification and separation are carried out in two ion-exchange chromatographic steps followed by derivatization and GC-MS. The within-assay imprecision values vary 3.1-9.6% and the between-assay imprecision 7.0-21.2%. The mean recovery of authentic standards processed through the whole procedure varied from 95.5 to 105.5%. Values for some different food samples are presented. The simultaneous determination of the biologically most interesting phytoestrogens and lignans in foods has not been carried out previously and the method will be useful for screening of important foods in populations with different risk of cancer and coronary heart disease, and for metabolic studies.
The isoflavonoids, genistein (4',5,7-trihydroxyisoflavone), biochanin A (5,7-dihydroxy-4'-methoxyisoflavone), daidzein (4',7-dihydroxyisoflavone), and formononetin (7-hydroxy-4'-methoxyisoflavone) are supposed to be health-promoting dietary factors of plant origin. They are particularly abundant in seeds and other parts of many plant species belonging to Leguminosae. The most popular source of isoflavonoids in human diet is soy. Here, evidence is presented that isoflavonoids are regularly found in beer. Diethyl ether extracts of beer were fractionated on thin-layer chromatography-silica, (straight phase) and rechromatographed using a reversed phase high-performance liquid chromatography octadecylsilica column. The fractions were analyzed by two recently developed radioimmunoassays, the first of them being specific for diadzein/formononetin and the second one specific for genistein/biochanin A. The immunoreactivity was found only in fractions with the mobility corresponding to the positions of standards on control chromatograms. Additionally, 26 samples of bottled beer were analyzed for isoflavonoid content using the combination of reversed phase high-performance liquid chromatography and radioimmunoassay. The sum of the four isoflavonoids ranged from 1.26 to 29 nmol/L in individual beers. Formononetin was the major isoflavonoid (0.19-14.99 nmol/L), whereas the concentration of daidzein was several times lower (0.08-2.5 nmol/L). Genistein and biochanin A concentrations were comparable, ranging from 0.169-6.74 nmol/L and from 0.820-4.84 nmol/L for genistein and biochanin A, respectively. It is concluded that beer contains significant amounts of biologically active isoflavonoid phytoestrogens.
In the last several years, attention has been focused on comparing the Western diet, which is rich in fat, protein, and refined carbohydrates, with the Asian diet, which is rich in phytoestrogens, as a possible explanation for the contrasting rates of clinically relevant prostate cancer. Phytoestrogens, plant-derived nutrients, include several isoflavones, flavonoids, lignans, phytosterols, and coumestans, some of which have been postulated as having anticarcinogenic properties. Using a new database, we examined the role of phytoestrogen intake and prostate cancer risk in 83 Caucasian cases and 107 controls. Controls reported consuming higher amounts of foods containing genistein, daidzein, and coumestrol and lower amounts of foods containing campesterol and stigmasterol. Multivariate analysis, after adjustment for age, family history of prostate cancer, alcohol consumption, and total calorie intake, showed an inverse association between coumestrol (p = 0.03) and daidzein (p = 0.07) and prostate cancer risk. Genistein, the most studied phytoestrogen, showed a slight protective effect (p = 0.26). However, a positive association was found between campesterol (p = 0.08) and stigmasterol (p = 0.03) and risk of prostate cancer. These results are suggestive of a possible relationship between phytoestrogen intake and prostate cancer risk. Larger comprehensive studies are needed to further refine the role of phytoestrogen intake in prostate cancer risk.
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.
To develop a dietary assessment instrument to measure soy food consumption and isoflavone intake and test it for reliability.
A soy food frequency questionnaire, designed for use in this study, was administered twice to participants, separated by a 2-week interval. The questionnaire was tested for reproducibility of estimates of soy food consumption and isoflavone (genistein and daidzein) intake.
A convenience sample of 51 faculty, staff, and students was recruited from a naturopathic university.
Intraclass correlation coefficients were used to assess reproducibility of estimates of soy food intake and genistein and daidzein intake.
Correlation coefficients comparing mean soy food servings per month between the 2 administrations of the questionnaire ranged from 0.50 for soy yogurt to 0.89 for tempeh. Correlation coefficients for genistein and daidzein intake estimated by the 2 administrations of the questionnaire were the same: 0.89. Mean intake (+/- standard deviation) of genistein and daidzein was 7 +/- 10 and 4 +/- 6 mg/day, respectively. Fifteen soy foods contributed 95% of the total genistein and daidzein intake: tofu, soy yogurt, tempeh, soy milk, low-fat tofu, soy flour, miso, soy protein isolate, low-fat soy milk, veggie soy burger, textured vegetable protein, miso soup, cooked soybeans, soy hot dogs, and natto (fermented soy beans).
The soy food frequency questionnaire developed in this study provided highly reproducible estimates of soy food consumption and isoflavone intake. This instrument may be a useful tool in studies of the associations between isoflavone exposure and risk for chronic disease.
Plants abound in essential phytochemicals produced for their various vital functions. The same compounds seem also to be crucial for human health and disease. Recent human epidemiological and laboratory animal and cell studies on cancer and heart disease have highlighted the phytoestrogens--naturally occurring principles that share with steroidal oestrogens an ability to activate oestrogen receptors. The best known non-steroidal phytoestrogens include the isoflavones daidzein, genistein, formononetin and biochanin A, the coumestan coumestrol, and the lignans secoisolariciresinol and matairesinol. Acknowledging the potentially chemoprotective role of these non-nutrients, we have quantified all biologically important isoflavonoids and lignans in cereals, oilseeds and nuts, legumes, vegetables, fruits, berries and beverages such as tea, coffee and wine. In this chapter, we present a review of our studies on staple plant foods, indicating that plants contain, besides a wide range of chemicals with a number of biological properties, biologically active phytoestrogens--precursors of hormone-like compounds found in mammalian systems.
In The Netherlands, part of the population experienced food restriction and severe famine during World War II. The purpose of this study was to study the effects of severe undernutrition during adolescence on the risk of breast cancer later in life.
We examined the hypothesis in the Netherlands Cohort Study on diet and cancer (NLCS), among 62,573 women aged 55-69 years. Baseline information on diet and other risk factors was collected with a questionnaire in 1986. Information was collected on residence in the Hunger winter (1944-1945) and War years (1940-1944) and fathers' employment status in 1932-1940 as indicators of exposure. After 6.3 years of follow-up, 1009 incident breast cases were available for analysis.
In multivariate case-cohort analysis, residents of the western part of the country in 1944-1945 had an increased breast cancer risk (western city RR = 1.1, 95% CI: 0.9-1.4, western rural area RR = 1.5, 95% CI: 1.1-1.9). For the War years (1940-1944) we found no association between breast cancer risk and urban vs. rural residence. Women whose fathers were unemployed during the Depression years (1932-1940) had a non-significant decrease in breast cancer risk (RR = 0.9, 95% CI: 0.7-1.2). Exposure to energy restriction during the adolescent growth spurt or during the period between menarche and birth of the first child did not change the RRs substantially.
We found no clear evidence in this study for the hypothesis that energy restriction in adolescence leads to a decreased breast cancer risk.
The antioxidant activities of the flaxseed lignan secoisolariciresinol diglycoside (SDG) and its mammalian lignan metabolites, enterodiol (ED) and enterolactone (EL), were evaluated in both lipid and aqueous in vitro model systems. All three lignans significantly (p < or = 0.05) inhibited the linoleic acid peroxidation at both 10 and 100 microM over a 24-48 h of incubation at 40 degrees C. In a deoxyribose assay, which evaluates the non site-specific and site-specific Fenton reactant-induced *OH scavenging activity, SDG demonstrated the weakest activity compared to ED and EL at both 10 and 100 microM; the greatest *OH scavenging for ED and EL was observed at 100 microM in both assays. The incubation of pBR322 plasmid DNA with Fenton reagents together with SDG, ED or EL showed that the inhibition of DNA scissions was concentration dependent. The greatest non site-specific activity of lignans was at 100 microM, thus, confirming the results of the deoxyribose test. In contrast, the protective effect of SDG and EL in the site-specific assay was lost and that of ED was minimal. Therefore, the results indicate a structure-activity difference among the three lignans with respect to specific antioxidant efficacy. All three lignans did not exhibit reducing activity compared to ascorbic acid, therefore, did not possess indirect prooxidant activity related to potential changes in redox state of transition metals. The efficacy of SDG and particularly the mammalian lignans ED and EL to act as antioxidants in lipid and aqueous in vitro model systems, at relatively low concentrations (i.e. 100 microM), potentially achievable in vivo, is an evidence of a potential anticarcinogenic mechanism of flaxseed lignan SDG and its mammalian metabolites ED and EL.
We recently described the development of a comprehensive database for assessing phytoestrogen exposure in epidemiologic studies. This paper describes the first application of this database and the primary sources of phytoestrogen consumption in non-Asian women.
Four hundred and forty-seven randomly selected African-American, Latina, and white women, ages 50-79 years, residing in California's San Francisco Bay Area and participating as controls in an ongoing population-based case-control study of breast cancer, were included in the present analysis. Average daily consumption of each of seven phytoestrogenic compounds was determined for each woman by combining the values from the new database with food consumption reported on a food-frequency questionnaire.
Phytoestrogens in the non-Asian Bay Area diet appear to come primarily from: (1) traditional soy-based foods (e.g. tofu and soy milk); (2) "hidden" sources of soy (e.g. foods containing added soy protein isolate, soy concentrate, or soy flour, e.g. many brands of doughnuts and white bread); and (3) a variety of foods which contain only low to moderate amounts of phytoestrogens per 100 grams but which are frequently consumed (e.g. coffee and orange juice).
In the absence of a comprehensive assessment of various phytoestrogens in a wide variety of foods, epidemiologic studies could suffer from the effects of uncontrolled confounding by unmeasured sources of phytoestrogen exposure potentially leading to biased estimates of effect and misinterpretation of findings.
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.
Quantitative data on phyto-oestrogen, particularly lignan, content in edible plants are insufficient. We, therefore, measured isoflavonoids and lignans in nine edible berries using an isotope dilution gas chromatography-mass spectrometry method for foods and found substantial concentrations of the lignan secoisolariciresinol (1.39-37.18 mg/kg DM), low amounts of matairesinol (0-0.78 mg/kg DM) and no isoflavones. To determine pharmacokinetics and urinary excretion pattern of the mammalian lignan enterolactone derived from plant lignans, a study with human subjects was conducted. Five healthy women and two men consumed, after a 72 h period of a phyto-oestrogen-free regimen, a single strawberry-meal containing known amounts of plant lignans. Basal and post-meal blood and urine samples were collected at short intervals. The samples were analysed using time-resolved fluoroimmunoassay of enterolactone. The meal increased plasma concentration of enterolactone after 8-24 h and in urine in the 13-24 h and 25-36 h urine collections. High individual variability of the metabolic response was observed. Enterolactone excreted in the urine collected throughout the 48 h post-meal yielded on average 114% of the plant lignans consumed. It is concluded that berries containing relatively high concentrations of plant lignans contribute to plasma and urinary levels of mammalian enterolactone in human subjects.
Samples of commercially prepared white, whole wheat, flax, and multigrain breads were analyzed by a rapid RP-HPLC method for the presence of the lignan secoisolariciresinol diglucoside (SDG). SDG was detected only in products containing flax, with concentrations ranging from 0.06 to 1.98 microM/g of DW (19-602 microM/loaf). Full-fat flax meal, powdered aqueous alcohol extracts of flax seed, and SDG were added to a white bread mix and baked into loaves in a domestic bread maker. Quantitative recovery of SDG from the test breads was observed when SDG was added; however, when flax meal or aqueous alcohol extracts were added, only 73-75% of the theoretical yield of SDG was recovered. SDG was also detected in commercially prepared flax cookies, bagels, and muffins with concentrations ranging from 0.26 to 2.93 microM/g of DW. The extent of grinding of the flax seed was also shown to have a significant effect on the recovery of SDG from both flax meal breads and baked goods, with extraction of SDG from finely ground samples greater than that from course material.
Dietary phytoestrogens such as the isoflavones daidzein and genistein are thought to protect against chronic diseases that are common in Western societies, such as cancer, osteoporosis, and ischemic heart disease. In addition, there are concerns regarding the deleterious effects of hormone-like compounds, especially with respect to the development of infants. However, there is little information regarding the phytoestrogen content of foods, and therefore epidemiologic investigations of phytoestrogens are limited. As part of a study quantifying the consumption of phytoestrogens, the objective of this work was to assess the daidzein and genistein content of fruits and nuts commonly eaten in Europe. Eighty different fruits and nuts were sampled, prepared for eating, and freeze-dried. Daidzein and genistein were extracted from the dried foods, and the two isoflavones were quantified after hydrolytic removal of any conjugated carbohydrate. Completeness of extraction and any procedural losses of the isoflavones were accounted for using synthetic daidzin (7-O-glucosyl-4'-hydroxyisoflavone) and genistin (7-O-glucosyl-4'5-dihydroxyisoflavone) as internal standards. Of the 80 foods assayed, 43 contained no detectable daidzein or genistein, at a limit of quantification of 1 microg/kg dry weight of food. Nine foods contained more than 100 microg of the two isoflavones combined per kilogram wet weight, and 28 contained less than this amount. Currants and raisins were the richest sources of the isoflavones, containing 2,250 microg and 1,840 microg of the two isoflavones combined per kilogram of wet weight of food. Although fruits and nuts are not as rich in isoflavone phytoestrogens as are soy and other legumes, this is the first documentation of levels of daidzein and genistein occurring in these foods.
The lignan family of natural products includes compounds with important antineoplastic and antiviral properties such as podophyllotoxin and two of their semisynthetic derivatives, etoposide and teniposide. The latter are included in a wide variety of cancer chemotherapy protocols. Due to these biological activities, lignans, and especially cyclolignans, have been the objective of numerous studies focused to prepare better and safer anticancer drugs. The mechanism by which podophyllotoxin blocks cell division is related to its inhibition of microtubule assembly in the mitotic apparatus. However, etoposide and teniposide were shown not to be inhibitors of microtubule assembly which suggested that their antitumor properties were due to another mechanism of action, via their interaction with DNA and inhibition of DNA topoisomerase II. Other podophyllotoxin derivatives has also been reported which retained or even improved the cytotoxic activity, but these were weak inhibitors of topoisomerase II in vitro; the data revealed that such analogs exhibit a different, as yet unknown, mechanism of action. The main deficiency of these compounds is their cytotoxicity for normal cells and hence side effects derived from their lack of selectivity against tumoral cells. In this regard it is necessary to investigate and prepare new more potent and less toxic analogs, that is, with better therapeutic indices. It is well accepted from structure-activity studies in this field that the trans-lactones are more potent as antineoplastics than the cis-lactones. Not only the configuration of the D ring is an important factor for high cytotoxic activity, but also a quasi-axial arrangement of the E ring is necessary. On this basis, studies on lignans have been addressed to modify the lactone moiety and prepare analogs with heteroatoms at different positions of the cyclolignan skeleton. Our group has been working during the last few years on chemical transformations of podophyllotoxin and analogs and we have prepared a large number of cyclolignan derivatives some of which display potent antiviral, immunosuppressive and cytotoxic activities. We have reported several new cytotoxic agents with nitrogen atoms at C-7 or C-9 or at both C-7 and C-9: imine derivatives, oxime derivatives, pyrazoline-, pyrazo- and isoxazoline-fused cyclolignans. At present, we are preparing mainly new compounds by modifications of the A and E cyclolignan-rings. They are being tested on cultures of different tumoral cell lines (P-388 murine leukemia, A-549 human lung carcinoma, HT-29 human colon carcinoma and MEL-28 human melanoma) and some of them have shown an interesting and selective cytotoxicity.
Food samples (n 114) were prepared from vegetables commonly eaten in Europe. The glycosidic forms of the phyto-oestrogens daidzein and genistein were extracted from the dried foods into aqueous methanol. The isoflavones were quantified by GC-MS after hydrolytic removal of any conjugated carbohydrate. Completeness of extraction and any procedural losses of the isoflavones were accounted for using synthetic daidzin (7-O-glucosyl-4'-hydroxyisoflavone) and genistin (7-O-glucosyl-4'5-dihydroxyisoflavone) as internal standards. Of the 114 foods assayed, at a limit of quantification of 0.1 microg/kg dry weight, forty-eight contained no detectable daidzein or genistein, forty-one contained less than 100 microg/kg of the two isoflavones combined and the remaining twenty-five contained more than this amount. Soyabean products contained between 470 and 1420 mg (average of 960 mg) daidzein and genistein combined per kg wet weight of food, and legumes contained between 20 and 5750 microg/kg wet weight of food, with an average of 620 microg/kg. Cooking by boiling in water caused a decrease in the daidzein and genistein content of food in twenty-four of twenty-eight foods. The extent of the decrease was variable and warrants further investigation. The present paper comprises the first comprehensive description of the content of daidzein and genistein in vegetables.
Many experimental but few epidemiological studies have suggested that soyfoods and their constituents have cancer-inhibitory effects on breast cancer. No epidemiological study has evaluated the association of adolescent soyfood intake with the risk of breast cancer. To evaluate the effect of soyfood intake during adolescence, one of the periods that breast tissue is most sensitive to environmental stimuli, on subsequent risk of breast cancer, we analyzed data from a population-based case-control of 1459 breast cancer cases and 1556 age-matched controls (respective response rates were 91.1% and 90.3%). Information on dietary intake from ages 13-15 years was obtained by interview from all study participants and, in addition, from mothers of subjects less than 45 years of age (296 cases and 359 controls). Odds ratios (ORs) and 95% confidence intervals (CIs) derived from unconditional logistic models were used to measure soyfood intake and breast cancer risk. After adjustment for a variety of other risk factors, adolescent soyfood intake was inversely associated with risk, with ORs of 1.0 (reference), 0.75 (95% CI, 0.60-0.93), 0.69 (95% CI, 0.55-0.87), 0.69 (95% CI, 0.55-0.86), and 0.51 (95% CI, 0.40-0.65), respectively, for the lowest to highest quintiles of total soyfood intake (trend test, P < 0.001). The inverse association was observed for each of the soyfoods examined and existed for both pre- and postmenopausal women. Adolescent soyfood intakes reported by participants' mothers were also inversely associated with breast cancer risk (P for trend < 0.001), with an OR of 0.35 (95% CI, 0.21-0.60) for women in the highest soyfood intake group. Adjustment for rice and wheat products, the major energy source in the study population, and usual adult soyfood intake did not change the soyfood associations. Our study suggests that high soy intake during adolescence may reduce the risk of breast cancer in later life.
The lignan enterolactone, which is produced by the intestinal microflora from dietary precursors, may protect against hormone-dependent cancers and cardiovascular diseases.
We examined the cross-sectional associations between the serum enterolactone concentration and variables related to diet and health in Finnish adults.
Serum enterolactone was measured by using time-resolved fluoroimmunoassay in 2380 Finnish men and women aged 25-64 y who were participating in a cross-sectional national survey in 1997. Background information was collected with self-administered questionnaires and the diet was assessed with a food-frequency questionnaire.
The median serum enterolactone concentration was 13.8 nmol/L (range: 0-95.6 nmol/L) in men and 16.6 nmol/L (range: 0-182.6 nmol/L) in women. Multiple regression analyses showed positive associations in men between the serum enterolactone concentration and constipation, consumption of whole-grain products, and intake of fruit and berries. In women, the serum enterolactone concentration was positively and independently associated with consumption of vegetables, subject age, and constipation and was negatively associated with smoking. Furthermore, female subjects of normal weight had significantly higher serum enterolactone concentrations than did their underweight or obese peers.
The serum enterolactone concentration varies widely in the population. Of the variables we examined, the most important determinants of the serum enterolactone concentration were consumption of lignan-containing foods and constipation; however, these appeared to explain only a small part of the variation. Therefore, the role of gut microflora in the metabolism of lignans might be very important. Further studies will also be needed to determine the bioavailability and absorption rate of lignans.
Many plants that are consumed contain phytoestrogens. Only a few published studies have examined the dietary intake of phytoestrogens in the general Western population. The potentially positive health effects of phytoestrogens might be of relevance to postmenopausal women. The aim of the present study was to estimate the intake of dietary isoflavones, coumestans and lignans by healthy Western postmenopausal women. For this purpose, we studied 964 postmenopausal, Caucasian women who participated in the Framingham Offspring Study and completed the Willett food-frequency questionnaire (FFQ). By searching the medical and agricultural literature and contacting experts, we identified food sources of phytoestrogens. The concentrations of the different isoflavones, coumestrol and lignans in each food in the FFQ were scored in seven categories and multiplied by the serving size of the food and the frequency of its consumption. The estimated daily median intake of the isoflavone daidzein was 39 microg (24-57 microg); of genistein, 70 microg (28-120 microg); of formononetin, 31 microg (13-44 microg); and of biochanin A, 6 microg (2-11 microg). Median total intake of isoflavones was 154 microg (99-235 microg). The main sources of isoflavones were beans and peas. The estimated daily intake of coumestans was 0.6 microg (0.2-1.7 microg), with broccoli as the main source. The estimated daily median intake of matairesinol was 19 microg (12-28 microg) and of secoisolariciresinol 560 microg (399-778 microg). The median total intake of lignans was 578 microg (416-796 microg). The main source of the lignans was fruits. The daily dietary intake of phytoestrogens in healthy postmenopausal Caucasian women in the United States is <1 mg.
Research on the relation between phytoestrogens and breast cancer risk has been limited in scope. Most epidemiologic studies have involved Asian women and have examined the effects of traditional soy foods (e.g., tofu), soy protein, or urinary excretion of phytoestrogens. The present study extends this research by examining the effects of a spectrum of phytoestrogenic compounds on breast cancer risk in non-Asian US women. African-American, Latina, and White women aged 35-79 years, who were diagnosed with breast cancer between 1995 and 1998, were compared with women selected from the general population via random digit dialing. Interviews were conducted with 1,326 cases and 1,657 controls. Usual intake of specific phytoestrogenic compounds was assessed via a food frequency questionnaire and a newly developed nutrient database. Phytoestrogen intake was not associated with breast cancer risk (odds ratio = 1.0, 95% confidence interval: 0.80, 1.3 for the highest vs. lowest quartile). Results were similar for pre- and postmenopausal women, for women in each ethnic group, and for all seven phytoestrogenic compounds studied. Phytoestrogens appear to have little effect on breast cancer risk at the levels commonly consumed by non-Asian US women: an average intake equivalent to less than one serving of tofu per week.
Application of stable and radioisotope precursor/tracer experiments resulted in the identification of various phenylpropanoid, monolignol, and lignan metabolites involved in the biosynthesis of the cancer chemopreventive secoisolariciresinol diglucoside (SDG; 1)-containing ester-linked "polymer(s)" in flax (Linum usitatissimum) seed. Individual analysis of size-segregated flax seed capsules at five early stages of their development provided a metabolic profile of intermediates leading to "biopolymer" biosynthesis. The use of (1)H and (13)C NMR and HRMS analyses resulted in the identification of 6a-HMG (hydroxymethyl glutaryl) SDG (17) and 6a,6a'-di-HMG SDG (18) as the two major components of the ester-linked "biopolymer(s)". Based on metabolic tracer analyses and relative radioisotopic incorporations throughout each of these five stages of seed development, a biochemical pathway is proposed from phenylalanine to SDG (1), with subsequent mono- and di-substitutions of SDG (1) with HMG CoA. These metabolites then serve as precursors for formation of the SDG-HMG ester-linked oligomers. Results from this study will facilitate future isolation and characterization of the proteins and enzymes involved in biosynthesis of the SDG-HMG ester-linked oligomers in flax seed.
Enterolactone is a lignan produced by fermentation of dietary precursors in the human gut. Because lignan precursors are uniquely found in plant foods, plasma enterolactone concentration may serve as a biological marker of plant food consumption. This cross-sectional study examined associations of dietary intake with plasma enterolactone concentration. Weight-stable, 20-40-year-old volunteers (115 women and 78 men in Seattle, Washington) reporting intake of < or =2.5 or > or =4.5 fruit and vegetable servings/day and no antibiotic use for > or =3 months completed a food frequency questionnaire and 3-day food record. Time-resolved fluoroimmunoassay was used to measure plasma enterolactone. Based on diet records, plasma enterolactone was positively correlated with daily vegetable servings (r = 0.17; P < 0.05), fiber (r = 0.36; P < 0.0001), alcohol (r = 0.24; P < 0.001), caffeine (r = 0.21; P < 0.001), and daily botanical group servings [Chenopodiaceae (r = 0.15; P < 0.05), Juglandaceae (r = 0.15; P < 0.05), Leguminosae (r = 0.20; P < 0.001), Pedaliaceae (r = 0.20; P < 0.001), and Vitaceae (r = 0.20; P < 0.001)]. Fat-related variables were not correlated with plasma enterolactone. Based on linear regression models, plasma enterolactone increased by 37.0% (SE = 2.3%) for each 10-g increase in fiber and by 6.6% (SE = 0.2%) for each 50-mg serving of caffeine. Participants consuming 0.5-1 alcoholic drink/day had plasma enterolactone concentrations that were 131.4% (SE = 37.6%) higher than those of nondrinkers. Although plasma enterolactone may be useful as a biological measure of exposure to lignan-containing foods, it may be of limited use as a specific biomarker of fruit and vegetable or plant food intake because coffee, tea, and alcoholic beverages also significantly increase its plasma concentration.