Dietary Lignans Research Articles

Impact of lignans in oilseed mix on gut microbiome composition and enterolignan production in younger healthy and premenopausal women: an in vitro pilot study

BackgroundDietary lignans belong to the group of phytoestrogens together with coumestans, stilbenes and isoflavones, and themselves do not exhibit oestrogen-like properties. Nonetheless, the gut microbiota converts them into enterolignans, which show chemical similarity to the human oestrogen molecule. One of the richest dietary sources of lignans are oilseeds, including flaxseed. The aim of this pilot study was to determine the concentration of the main dietary lignans in an oilseed mix, and explore the gut microbiota-dependent production of enterolignans for oestrogen substitution in young and premenopausal women. The oilseed mix was fermented in a pH-controlled batch culture system inoculated with women’s faecal samples. The lignan content and enterolignan production were measured by ultra‐high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS), and the faecal-derived microbial communities were profiled by 16S rRNA gene-based next-generation sequencing.ResultsIn vitro batch culture fermentation of faecal samples inoculated with oilseed mix for 24 h resulted in a substantial increase in enterolactone production in younger women and an increase in enterodiol in the premenopausal group. As for the gut microbiota, different baseline profiles were observed as well as different temporal dynamics, mainly related to Clostridiaceae, and Klebsiella and Collinsella spp.ConclusionsDespite the small sample size, our pilot study revealed that lignan-rich oilseeds could strongly influence the faecal microbiota of both younger and premenopausal females, leading to a different enterolignan profile being produced. Further studies in larger cohorts are needed to evaluate the long-term effects of lignan-rich diets on the gut microbiota and find out how enterolactone-producing bacterial species could be increased. Diets rich in lignans could potentially serve as a safe supplement of oestrogen analogues to meet the cellular needs of endogenous oestrogen and deliver numerous health benefits, provided that the premenopausal woman microbiota is capable of converting dietary precursors into enterolignans.

Abstract MP68: Dietary Lignan and Cardio-metabolic Risk: Exploring the Role of the Gut Microbiome

Background and Study Purpose: The conversion of plant lignans to enterolignans for absorption is mediated through the gut microbiota. We explored the interconnections between the intake of dietary lignans, circulating concentrations of plasma enterolignans, the gut microbiome, and cardio-metabolic risk factors (LDL-cholesterol, HDL-cholesterol, & triglycerides). Design and method: The study was a repeated cross-sectional survey of up to 4 stool samples. Dietary lignan intake was assessed by two 7 day weighed records administered to coincide with fecal sample collection. DNA was extracted from 916 samples provided by 301 participants, and RNA was extracted from 369 samples from a subgroup of 96 participants. P<0.25 after false discovery rate correction was considered statistically significant. Results: A high ratio of plasma enterolactone to dietary lignan was significantly associated with the relative abundance of 35 species (24 enriched and 11 depleted species), including 8 Bacteroidetes and 13 Firmicutes species. Greater dietary lignan was only significantly associated with a lower plasma ratio of triglyceride to HDL when plasma enterolactone was high. The association between dietary lignans and ratio of TG to HDL was mainly mediated by plasma enterolactone level (mediation effect: 74.3%, P=0.002), which was partially captured by the weighted species score (mediation effect: 28.6%, P=0.02). We observed several significant interactions between dietary lignans and presence of species on ratio of TG to HDL, suggesting that the protective effect of dietary lignans on CVD risk factor depends on the presence/abundance of certain microbiota. The relative abundance of microbial pathways involved in I-isoleucine biosynthesis and glutaryl-coa degradation pathways were significantly greater in in participants with a higher level of plasma enterolactone. Conclusion: The health benefits of dietary lignans on lipid levels may be modified by the greater enrichment of biologically relevant microbiota species. FIGURE

Abstract P2-13-19: Validation of a Chinese-specific food frequency questionnaire for assessing dietary lignans intake among breast cancer patients in Hong Kong

Abstract Background: Lignans intake has been suggested to affect breast cancer outcomes based on a few studies from the West. However, to date, the relationship of lignan consumption and breast cancer outcomes has not been investigated in Chinese patient population. Since the habitual intake of lignan and food sources for lignan may vary between different geographical population and ethnicities, it is necessary to develop a population-specific Food Frequency Questionnaire (FFQ) to enable the conduct of dietary lignan studies in Chinese patient population. The objective of this study is to validate a modified FFQ that could be utilized for assessing lignan intake in a Chinese population. Methods: 133 Hong Kong Chinese women with early-stage breast cancer who were participating in an on-going prospective cohort study (The Hong Kong New Territories East Cluster (NTEC)-Kowloon West Cluster (KWC) Breast Cancer Survival Study) were being consented into the present study; the NTEC-KWC study investigates the associations of phytoestrogens and other factors with breast cancer outcomes. 103 of the 133 patients completed all the study assessments and were included in the analysis; they underwent two face-to-face interviews during which they responded to a modified 130-item FFQ at 1-year apart (FFQ1, FFQ2). In addition, 12 monthly 24-hour dietary recalls (24-h DRs) were conducted through telephone during the same 1-year period. Total lignans intake from the FFQs and 24-h DRs, correlation coefficients and cross classification between the two FFQs and between FFQ and 24-h DR were examined. Results: Median intakes of total lignans for FFQ1, FFQ2 and 24-h DRs were 2.39, 2.15 and 1.36 mg/day, respectively. Both the energy-adjusted correlation coefficients between FFQ1 and FFQ2, and that between FFQ2 and 24-h DR were 0.59 for log-transformed lignans intake (p<0.001). Correct classification of participants into the same quartiles of energy-adjusted lignans intake between 2 FFQs and between FFQ2 and 24-h DR were 37.9% and 40.8%, respectively. Misclassification of participants into the extreme quartiles occurred in 7.8% and 2.9% of the studied patients, respectively. The reproducibility between lignans intake assessed by the 2 FFQs conducted was 0.59 (p<0.001) for energy-adjusted lignans intake after log transformation. Conclusion: The 130-item FFQ has acceptable validity and reproducibility, and is a reasonable and useful instrument to assess dietary lignans intake among Hong Kong Chinese women with early-stage breast cancer. Funding: World Cancer Research Fund International (Grant Number WCRF 2010/249 and WCRF 2014/1197) Citation Format: Yiqian He, Yuan-Yuan Lei, Carol Kwok, Ashley Cheng, Ka-Li Cheung, Iris Lee, Roselle Lee, Suzanne Ho, Winnie Yeo. Validation of a Chinese-specific food frequency questionnaire for assessing dietary lignans intake among breast cancer patients in Hong Kong [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-19.

The Role of Gut Microbiome on Cardiovascular Health Benefits of Dietary Lignans (CardioFlax Study).

The Role of Gut Microbiome on Cardiovascular Health Benefits of Dietary Lignans (CardioFlax Study).

Effect of Roasting Process on Sesamin and Sesamol Contents of Sesame (Sesamum indicum L.) from Different Parts of Iran

Background and objectivesSesame (Sesamum indicum L.) seeds have been a well-known oil crop in the world for many centuries. Lignans are functionally important compartments of sesame. Sesamin and sesamol are the main sesame lignans, which have recently shown various activities with health benefits, like anti-oxidative, anti-proliferative, anti-atherosclerotic, anti-inflammatory and anticancer effects. The aim of this study was determination of sesamin and sesamol concentration in sesame seeds from three different regions of Iran with diverse climatic conditions (Dezful, Ardakan and Neka). In addition, the effect of roasting process on sesamin and sesamol content were investigated.MethodsAnalysis of sesamin and sesamol was performed using the mobile phase water: methanol (70:30) on a reversed phase ACE C18 with flow rate of 0.6 mL/min and UV detection at 290 nm.ResultsHPLC analysis revealed that the highest content of sesamin (1.156±0.002 mg/g of seeds) and sesamol (2.393±0.002 mg/g of seeds) were observed in roasted Dezful seeds samples and hulled roasted Dezful sesame seeds, respectively. The amount of sesamin and sesamol in roasted seeds was higher than unroasted samples.ConclusionThe present study showed that the roasting process and hot semi-arid climate increase the content of lignans in sesame seeds. Consuming sesame seeds with such characteristics will improve dietary lignan intake and has nutritive value. Moreover, sesame seed characterized by the highest amount of sesamin and sesamol is more strongly suggested for achieving biological properties of these components.

Colonic mucosal and exfoliome transcriptomic profiling and fecal microbiome response to a flaxseed lignan extract intervention in humans

Microbial metabolism of lignans from high-fiber plant foods produces bioactive enterolignans, such as enterolactone (ENL) and enterodiol (END). Enterolignan exposure influences cellular pathways important to cancer risk and is associated with reduced colon tumorigenesis in animal models and lower colorectal cancer risk in humans. The aim of this study was to test the effects of a flaxseed lignan supplement (50 mg secoisolariciresinol diglucoside/d) compared with placebo on host gene expression in colon biopsies and exfoliated colonocyte RNA in feces and fecal microbial community composition, and to compare responses in relation to ENL excretion. We conducted a 2-period randomized, crossover intervention in 42 healthy men and women (20-45 y). We used RNA-seq to measure differentially expressed (DE) genes in colonic mucosa and fecal exfoliated cells through the use of edgeR and functional analysis with Ingenuity Pathway Analysis. We used 16S ribosomal RNA gene (V1-V3) analysis to characterize the fecal microbiome, and measured END and ENL in 24-h urine samples by gas chromatography-mass spectrometry. We detected 32 DE genes (false discovery rate <0.05) in the exfoliome, but none in the mucosal biopsies, in response to 60 d of lignan supplement compared with placebo. Statistically significant associations were detected between ENL excretion and fecal microbiome measured at baseline and at the end of the intervention periods. Further, we detected DE genes in colonic mucosa and exfoliome between low- and high-ENL excreters. Analysis of biopsy samples indicated that several anti-inflammatory upstream regulators, including transforming growth factor β and interleukin 10 receptor, were suppressed in low-ENL excreters. Complementary analyses in exfoliated cells also suggested that low-ENL excreters may be predisposed to proinflammatory cellular events due to upregulation of nuclear transcription factor κB and NOS2, and an inhibition of the peroxisome proliferator-activated receptor γ network. These results suggest that ENL or other activities of the associated gut microbial consortia may modulate response to a dietary lignan intervention. This has important implications for dietary recommendations and chemoprevention strategies. This study was registered at clinicaltrials.gov as NCT01619020.

Serum enterolactone concentrations are low in colon but not in rectal cancer patients

The dietary lignan metabolite, enterolactone, has been suggested to have anti-cancer functions, and high serum enterolactone concentrations have been associated with decreased risk of breast and prostate cancers. We hypothesized that serum enterolactone concentrations as a marker of plant-based foods are associated with decreased risk in colorectal cancer (CRC). We measured serum enterolactone glucuronide and sulfate concentrations by liquid chromatography-tandem mass spectrometry in 115 CRC patients and 76 sex- and age-matched controls and analyzed the results with respect to tumor parameters, clinical parameters, and systemic inflammatory markers. Patients with colon cancer had significant lower serum enterolactone glucuronide and sulfate concentrations than controls (glucuronide: median 3.14 nM vs. 6.32 nM, P < 0.001; sulfate: median 0.13 nM vs. 0.17 nM, P = 0.002), whereas rectal cancer patients had similar enterolactone levels as controls (glucuronide: median 5.39 nM vs. 6.32 nM, P = 0.357; sulfate: median 0.19 nM vs. 0.17 nM, P = 0.452). High serum enterolactone concentrations were associated with low tumor grade, high serum creatinine levels, and concomitant diabetes. In summary, our results suggest that serum enterolactone concentrations are decreased in colon but not in rectal cancer. Further investigations are required to assess whether this reflects an altered lignan metabolism by the colon microbiome.

Dietary Lignans: Definition, Description and Research Trends in Databases Development.

The study aims to communicate the current status regarding the development and management of the databases on dietary lignans; within the phytochemicals, the class of the lignan compounds is of increasing interest because of their potential beneficial properties, i.e., anticancerogenic, antioxidant, estrogenic, and antiestrogenic activities. Furthermore, an introductory overview of the main characteristics of the lignans is described here. In addition to the importance of the general databases, the role and function of a food composition database is explained. The occurrence of lignans in food groups is described; the initial construction of the first lignan databases and their inclusion in harmonized databases at national and/or European level is presented. In this context, some examples of utilization of specific databases to evaluate the intake of lignans are reported and described.

Heterosis, lipid profile and lignan glycosides assessment in raised inter-varietal promising hybrids of sesame (Sesamum indicum L.; Pedaliaceae)

Seven desirable hybrids (based on fatty oil content) namely RTH2, RTH5 and RTH7 (roma × tilottama), SRH1, SRH2, SRH3 (savitri × roma) and STH2 (savitri × tilottama) of Sesamum indicum L. (Family: Pedaliaceae; commonly known as sesame, an important oil seed crop of commerce) are selected from twenty intervarietal hybrids (tilottama — black seed coat; roma — brown seed coat and savitri — white seed coat) raised through natural crossing following interplanting (15 cm and 30 cm between plants and rows respectively). Seed coat color is used as marker trait for hybrid identification. Heterosis (mid parent heterosis, heterobeltosis and standard heterosis) is measured in F1, F2 and F3 (raised following selfing) generations considering seed yield and yield contributing (plant height, number of primary and total branches per plant, capsules per plant and seeds per capsule) traits. Considering heterosis and inbreeding depression it seems that RTH2 is the most promising hybrid. F3 harvested seeds are used to assess fatty acid profile and oil soluble lignan contents (sesamin and sesamolin detected from virgin sesame oil) in the studied hybrids. Result highlights the following: (1) significant enhancement in seed yield across generations in RTH2, RTH5 and SRH3, (2) identification of behenic acid (C22:0) fraction pioneerly in sesame fatty oil (tilottama, roma, savitri, RTH5 and RTH7), (3) SRH2 hybrid shows most promising fatty acid profile comprising of balance proportion of ω-6:ω-9 fatty acid (1:1) and enhance ω-3 fatty acid content desirable for human health and (4) SRH1 hybrid as the most promising germplasm in relation to dietary lignan content. Pure lines of the hybrids in later segregating generation can be more desirable for commercial exploitation.

Urinary Lignan Levels and Thyroid Function in Adults from NHANES 2007-2010

Background: Enterodiol and enterolactone are lignans, a group of phytoestrogens produced by bacteria in the colon that act on plant precursors. Flaxseed is the largest dietary source of lignans, but are also found in other seeds, grains, fruits, and vegetables. Health effects research on enterodiol and enterolactone is limited. However, some studies find associations between high dietary lignan exposure and reduced risk of thyroid and breast cancer and cardiovascular disease.Method: We performed a cross-sectional analysis examining the relation between urinary lignan concentrations and serum of thyroid levels in adults free of thyroid disease in the National Health and Nutrition Examination Survey (2007-2010). Specifically, we conducted multivariable analyses relating the concentrations of each urinary lignan (enterodiol, enterolactone) to serum concentrations of thyroid stimulating hormone [TSH], free triiodothyronine [T3], total T3, free thyroxine [T4], total T4, thyroperoxidase [TPO] antibodies, adjusting for sociodemographics, creatinine, iodine and thiocyanate.Results: In women, enterodiol and enterolactone were inversely associated with total T4. A 10-fold increase in enterodiol was associated with a 1.8% decrease (95% CI: -2.8%, -0.89%) in total T4, and a 10-fold increase in enterolactone was associated with a 1.6% decrease (95% CI: -2.5%, -0.68%) in total T4. Among men, a 10-fold increase in enterolactone was associated with a 1.0% increase (95% CI: -2.32%, 0.23%) in total T4 and a 10-fold increase in enterodiol was associated with a 2.1% decrease (95% CI: -3.4%, -0.82%) in total T4. In addition, among women, there was an inverse association between enterolactone and free T3, where a 10-fold increase in enterolactone was associated with a 1.6% decrease (95% CI: -2.5%, -0.68%) in free T3.Conclusion: In the present study, urinary lignan concentrations were associated with serum concentrations of selected thyroid hormones in a sex-dependent fashion.

Influence of different lignan compounds on enterolignan production by Bifidobacterium and Lactobacillus strains

Enterolignans, i.e. enterodiol and enterolactone, are polyphenols derived from the microbial metabolism of dietary lignans. They are considered phytoestrogens because of their estrogenic/antiestrogenic activity, which confers them benefits to human health when they reach sufficient levels in plasma. Hence, there is a great interest in studying the bacteria involved in enterolignan production. In the present study, three bifidobacterial strains (Bifidobacterium bifidum INIA P466, Bifidobacterium catenulatum INIA P732 and Bifidobacterium pseudolongum INIA P2) were found capable of producing low levels of enterodiol (2–11 μM) from lignan extracts; while another one (Bifidobacterium pseudocatenulatum INIA P946) was found to produce an important increment of the lignan secoisolariciresinol (SECO). Subsequently, the three enterodiol-producing bifidobacteria and another three Lactobacillus strains previously identified as enterolignans producers (Lactobacillus gasseri INIA P508, Lactobacillus salivarius INIA P448 and Lb. salivarius INIA P183), were tested on pure lignans yielding both enterodiol and enterolactone from secoisolariciresinol (SECO), while they did not metabolised the other lignan tested (i.e. matairesinol). B. catenulatum INIA P732 and Lb. gasseri INIA P508 were the strains that transformed the greatest percentage of SECO, yielding enterolactone concentrations above 2 mM. In addition, the formation of the intermediate compound dihydroxyenterodiol was observed as part of SECO transformation by all the strains. In this work, we have demonstrated for the first time how strains of Bifidobacterium and Lactobacillus are capable of carrying out the complete enterolignan metabolism, transforming a purified lignan (SECO) into enterodiol and enterolactone. The isolation and characterization of bacteria able to metabolize lignans and produce enterolignans, especially belonging to Bifidobacterium and Lactobacillus genera, is of biotechnological interest, because of their potential application in functional foods and as probiotics.

Gomisin A Suppresses Colorectal Lung Metastasis by Inducing AMPK/p38-Mediated Apoptosis and Decreasing Metastatic Abilities of Colorectal Cancer Cells.

Gomisin A (G.A) is a dietary lignan compound from Schisandra chinensis. In this study, the effect of G.A on the proliferation and metastasis of colorectal cancer (CRC) cells was investigated using several CRC cell lines and a lung metastasis mouse model. Both oral and intraperitoneal administration of G.A (50 mg/kg) inhibited lung metastasis of CT26 cells. Various concentrations of G.A were incubated with CRC cell lines and their viability was determined using a cell counting kit-8 assay. G.A significantly decreased the viability of various CRC cell lines, whereas it did not change the proliferation of normal colon cells. G.A induced G0/G1 phase arrest and apoptosis of CT26 and HT29 cells by regulating cyclin D1/cyclin-dependent kinase 4 (CDK4) expression and apoptotic proteins such as caspases and B-cell lymphoma-2 (Bcl-2) family proteins, respectively. G.A-induced apoptosis was mediated by AMPK/p38 activation in CRC cells. A non-cytotoxic concentration of G.A inhibited epithelial–mesenchymal transition of CRC cells by modulating E-cadherin and N-cadherin expression levels. Moreover, the migration and invasion of CRC cells were reduced by G.A treatment. Especially, G.A decreased matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities. G.A ameliorated lung metastasis of CRC cells by decreasing cell survival and metastatic abilities of CRC cells. Thus, G.A might be a potential novel therapeutic agent for metastatic CRC.

Are Total and Individual Dietary Lignans Related to Cardiovascular Disease and Its Risk Factors in Postmenopausal Women? A Nationwide Study.

The study objectives were to examine total and individual lignan intakes and their dietary sources in postmenopausal Polish women and to investigate the relationship between lignan intake and the prevalence of cardiovascular disease (CVD), hypertension, hypercholesterolemia and central obesity. A total of 2599 postmenopausal women, participants of the Multi-centre National Population Health Examination Surveys (WOBASZ and WOBASZ II) were selected. Of them, 916 had a history of CVD. Nutritional data were collected using a single 24-h dietary recall. Data on lignan content in food, i.e., lariciresinol (LARI), matairesinol (MAT), pinoresinol (PINO) and secoisolariciresinol (SECO), were collected from the available lignan databases. In postmenopausal women, total and individual lignan intakes (SECO, PINO, MAT) were not associated with the prevalence of CVD and its risk factors. The intake of LARI was linked by 30% to the reduced odds for hypercholestrolemia. This study reinforces the existing concept that dietary total lignans are not associated with the prevalence of CVD, and provides further evidence that they are not linked to CVD risk factors such as hypertension, hypercholesterolemia and central obesity. However, the intake of LARI should be taken into consideration in further studies with regard to its potentially beneficial effect in hypercholesterolemia.

An altered tissue distribution of flaxseed lignans and their metabolites in Abcg2 knockout mice.

Lignans are dietary polyphenols, which are metabolized by gut microbiota into the phytoestrogenic metabolites enterolignans, mainly enterolactone and enterodiol. Breast Cancer Resistance Protein (BCRP/ABCG2) is an efflux transporter that affects the plasma and milk secretion of several drugs and natural compounds. We hypothesized here that Abcg2 could influence the levels of lignans and their derived metabolites in target tissues. Consequently, we aimed to evaluate the role of Abcg2 in the tissue distribution of these compounds. We used Abcg2-/- knockout and wild-type male mice fed with a lignan-enriched diet for one week and analysed their plasma, small intestine, colon, liver, kidneys and testicles. High levels of lignans as well as enterolignans and their glucuronide and sulfate conjugates in the small intestine and colon were detected, with higher concentrations of the conjugates in the wild-type compared with Abcg2-/- mice. Particularly relevant was the detection of 24-fold and 8-fold higher concentrations of enterolactone-sulfate and enterolactone-glucuronide, respectively, in the kidney of Abcg2-/- compared with wild-type mice. In conclusion, our study showed that lignans and their derived metabolites were in vivo substrates of Abcg2, which affected their plasma and tissue levels. These results highlight the role of Abcg2 in influencing the health-beneficial properties of dietary lignans.

Oxidative rearrangement of (+)-sesamin by CYP92B14 co-generates twin dietary lignans in sesame

(+)-Sesamin, (+)-sesamolin, and (+)-sesaminol glucosides are phenylpropanoid-derived specialized metabolites called lignans, and are rich in sesame (Sesamum indicum) seed. Despite their renowned anti-oxidative and health-promoting properties, the biosynthesis of (+)-sesamolin and (+)-sesaminol remained largely elusive. Here we show that (+)-sesamolin deficiency in sesame is genetically associated with the deletion of four C-terminal amino acids (Del4C) in a P450 enzyme CYP92B14 that constitutes a novel clade separate from sesamin synthase CYP81Q1. Recombinant CYP92B14 converts (+)-sesamin to (+)-sesamolin and, unexpectedly, (+)-sesaminol through an oxygenation scheme designated as oxidative rearrangement of α-oxy-substituted aryl groups (ORA). Intriguingly, CYP92B14 also generates (+)-sesaminol through direct oxygenation of the aromatic ring. The activity of CYP92B14 is enhanced when co-expressed with CYP81Q1, implying functional coordination of CYP81Q1 with CYP92B14. The discovery of CYP92B14 not only uncovers the last steps in sesame lignan biosynthesis but highlights the remarkable catalytic plasticity of P450s that contributes to metabolic diversity in nature.

Influence of Flaxseed Lignan Supplementation to Older Adults on Biochemical and Functional Outcome Measures of Inflammation

ABSTRACT Evidence from the literature suggests that dietary flaxseed lignans have the ability to modulate inflammation, which is recognized as the underlying basis of multiple chronic human diseases in older adults. Our objective was to determine the effects of oral lignan supplementation on biochemical and functional indicators of inflammation as well as safety and tolerability in older healthy adults. We designed a randomized, double-blind, placebo-controlled clinical trial in older healthy adults (60–80 years) to assess flaxseed lignan–enriched complex (∼38% secoisolariciresinol diglucoside [SDG]; 600 mg SDG dose) oral supplementation effects on biochemical and functional indicators of inflammation and safety and tolerability in older healthy adults after 6 months of once-daily oral administration. The clinical trial confirmed that plasma concentration of total flaxseed lignans (free and conjugated forms) secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (ENL) were significantly associated with daily oral supplementation of flaxseed lignan–enriched complex (p < 0.05). A significant decrease in systolic blood pressure (SBP; from a mean of 155 ± 13 mm Hg at baseline to 140 ± 11 mm Hg at 24 weeks) was observed in lignan-supplemented participants stratified into an SBP ≥140 mm Hg subcategory (p = 0.04). No differences were found between treatment or placebo groups in terms of cognition, pain, activity, physical measurements (calf, waist, and upper arm circumstances), and grip strength. With respect to blood inflammatory markers, lipid profiles, and biochemical parameters, no significant differences were found between treatment and placebo groups at the end of the 6-month supplementation. No adverse effects were reported during supplementation. These data further support the safety and tolerability of long-term flaxseed lignan–enriched complex supplementation in older adults and identify an ability to favorably modulate SBP, an important risk factor in cardiovascular disease.

UHPLC-ESI-QTOF-MS screening of lignans and other phenolics in dry seeds for human consumption

Dry seeds are receiving increasing attention as functional foods, due to their high concentration of phenolic compounds and particularly of lignans. In this study, total phenolic content, antioxidant capacity and the whole phenolic profile of poppy, sunflower, pumpkin, sesame and flaxseed were determined. A deep profiling, firstly regarding phenolic compounds and then, more specifically, lignans, was carried out using liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS).All matrices were confirmed to be an excellent source of health-promoting compounds, although with marked differences. Sunflower is an excellent source of phenolics and showed the highest antioxidant capacity even though its lignan content is limited. Sesame and flaxseed provide a good source of phenolics, but their peculiar contribution is in term of lignans. Finally, pumpkin and poppy seeds contain a fair concentration of phenolics and a limited concentration of dietary lignans.

Effect of Antibiotics and Diet on Enterolactone Concentration and Metabolome Studied by Targeted and Nontargeted LC-MS Metabolomics.

High plant lignan intake is associated with a number of health benefits, possibly induced by the lignan metabolite enterolactone (ENL). The gut microbiota plays a crucial role in converting dietary lignans into ENL, and epidemiological studies have shown that use of antibiotics is associated with lower levels of ENL. Here we investigate the link between antibiotic use and lignan metabolism in pigs using LC-MS/MS. The effect of lignan intake and antibiotic use on the gut microbial community and the pig metabolome is studied by 16S rRNA sequencing and nontargeted LC-MS. Treatment with antibiotics resulted in substantially lower concentrations of ENL compared with concentrations detected in untreated animals, whereas the plasma concentrations of plant lignans were unchanged. Both diet and antibiotic treatment affected the clustering of urinary metabolites and significantly altered the proportions of taxa in the gut microbiota. Diet, but not antibiotic treatment, affected the plasma lipid profile, and a lower concentration of LDL cholesterol was observed in the pigs fed a high lignan diet. This study provides solid support for the associations between ENL concentrations and use of antibiotics found in humans and indicates that the lower ENL concentration may be a consequence of the ecological changes in the microbiota.

Prospective Study of Dietary Phytoestrogen Intake and the Risk of Colorectal Cancer

ABSTRACTDietary phytoestrogen intake has been inversely associated with the risk of prostate and breast cancer and might also affect the risk of colorectal cancer. We evaluated the associations between dietary lignan intake, dietary isoflavonoid intake, dietary coumestrol intake, and dietary enterolignans and equol intake, and risk of colorectal cancer. Data from the Women's Lifestyle and Health (WLH) Cohort study was used. The WLH study is a prospective population-based cohort study including 48,268 Swedish women aged 30–49 years at the time of enrolment in 1991–92. Follow-up for colorectal cancer incidence, death, and emigration until the end of 2010 was performed through record linkage to the Swedish Cancer Registry and Total Population Register. During follow-up 206 incident colorectal cancer cases were identified. Cox proportional hazards models were fitted to estimate adjusted risk ratios with 95% confidence intervals. We found no statistically significant association between the intake of dietary lignans, dietary isoflavonoids, coumestrol, or enterolignans and equol, and risk of colorectal cancer. We found no association between dietary phytoestrogen intake and the risk of colorectal cancer. However, since the number of cancer cases was small, our results need to be confirmed. Future studies should investigate colon and rectal cancer separately.

Antidiabetic effect of enterolactone in cultured muscle cells and in type 2 diabetic model db/db mice.

Enterolactone (ENL) is formed by the conversion of dietary precursors like strawberry lignans via the gut microbiota. Urinary concentrations of lignan metabolites are reported to be significantly associated with a lower risk of Type 2 diabetes (T2D). In the present study, antidiabetic effect of ENL and its modes of action were studied in vitro and in vivo employing a rat skeletal muscle-derived cell line, L6 myocytes in culture, and T2D model db/db mice. ENL dose-dependently increased glucose uptake in L6 myotubes under insulin absent condition. This increase by ENL was canceled by compound C, an inhibitor of 5'-adenosine monophosphate-activated protein kinase (APMK). Activation (=phosphorylation) of AMPK and translocation of glucose transporter 4 (GLUT4) to plasma membrane in L6 myotubes were demonstrated by Western blotting analyses. Promotion by ENL of GLUT4 translocation to plasma membrane was also visually demonstrated by immunocytochemistry in L6 myoblasts that were transfected with glut4 cDNA-coding vector. T2D model db/db mice were fed the basal 20% casein diet (20C) or 20C supplemented with ENL (0.001 or 0.01%) for 6weeks. Fasting blood glucose (FBG) levels were measured every week and intraperitoneal glucose tolerance test (IPGTT) was conducted. ENL at a higher dose (0.01% in 20C) suppressed the increases in FBG levels. ENL was also demonstrated to improve the index of insulin resistance (HOMA-IR) and glucose intolerance by IPGTT in db/db mice. From these results, ENL is suggested to be an antidiabetic chemical entity converted from dietary lignans by gut microbiota.