Cytotoxic activity of extracts from Tecoma species and isolated lignans

Abstract A phytochemical study of Tecoma genus (Bignoniaceae) was accomplished by antitumor activity of ethanolic extracts. Species of this genus are composed of small shrubs often used as ornamental plants. The Tecoma stans species is used in folk medicine for different purposes. Recent work shows in vitro anticancer activity against human breast cancer. The ethanolic extracts from leaves and trunks of Tecoma casneifolia, T. garrocha, T. stans var. angustata and T. stans var. stans were tested in vitro. The assays used were against line tumor cells by the MTT method and the most active extracts were further studied. In this way, the ethanolic extract from T. stans var. stans trunks presented the higher cytotoxicity against the tumor cell lines studied (CC50 0.02 to 0.55 µg/ml) when compared to the other extracts tested (CC50 0.08 to 200.0 µg/ml). Accordingly, this extract was selected for chromatographic fractionation from which five known lignans were isolated. Further, paulownin, paulownin acetate, sesamin, olivil and cycloolivil were identified using 13C and 1H NMR, IR, UV and spectroscopy and spectrometric MS techniques. These isolated compounds were tested and exhibited CC50 ranging from 13.01 to100.0 µg/ml which is superior to the ethanolic extract of trunk of T. stans

Flaxseed oil stimulates gynecomastia.

Flaxseed oil contains lignans, which exhibit anti-inflammatory and antiatherogenic activities. A 70-year-old male patient presented to our office due to hyperlipidaemia and started to take a tablespoon of flaxseed oil daily. Three months later, he reported left breast swelling and pain. Although the echogram revealed a tumour in the left mammary gland, the breast biopsy was compatible with gynecomastia, showing ductal hyperplasia without evidence of malignancy. His breast epithelia were oestrogen receptor-positive. Potential role of phytoestrogens was discussed.

Effects of Dietary Phytoestrogens on Hormones throughout a Human Lifespan: A Review.

Dietary phytoestrogens are bioactive compounds with estrogenic activity. With the growing popularity of plant-based diets, the intake of phytoestrogen-rich legumes (especially soy) and legume-derived foods has increased. Evidence from preclinical studies suggests these compounds may have an effect on hormones and health, although the results of human trials are unclear. The effects of dietary phytoestrogens depend on the exposure (phytoestrogen type, matrix, concentration, and bioavailability), ethnicity, hormone levels (related to age, sex, and physiological condition), and health status of the consumer. In this review, we have summarized the results of human studies on dietary phytoestrogens with the aim of assessing the possible hormone-dependent outcomes and health effects of their consumption throughout a lifespan, focusing on pregnancy, childhood, adulthood, and the premenopausal and postmenopausal stages. In pregnant women, an improvement of insulin metabolism has been reported in only one study. Sex hormone alterations have been found in the late stages of childhood, and goitrogenic effects in children with hypothyroidism. In premenopausal and postmenopausal women, the reported impacts on hormones are inconsistent, although beneficial goitrogenic effects and improved glycemic control and cardiovascular risk markers have been described in postmenopausal individuals. In adult men, different authors report goitrogenic effects and a reduction of insulin in non-alcoholic fatty liver patients. Further carefully designed studies are warranted to better elucidate the impact of phytoestrogen consumption on the endocrine system at different life stages.

Pharmacokinetics and liver uptake of three Schisandra lignans in rats after oral administration of liposome encapsulating ß-cyclodextrin inclusion compound of Schisandra extract.

Schisandra chinensis fructus (SCF) is widely used traditional Chinese medicine, which possesses hepato-protective potential. Schisandrin (SD), schisantherin (ST), and γ-schizandrin (SZ) are the major bioactive lignans. The main problem associated with the major bioactive lignans oral administration is low oral bioavailability due to the lignans' poor aqueous solubility and taste. The aim of the present research work was to develop liposome (SCL) encapsulated ß-cyclodextrin (ß-CD) inclusion complex loaded with SCF extract (SCF-E). The SD, ST, and SZ were selected as effective candidates to perform comparisons of liver targeting among the solution (SES), ß-cyclodextrin inclusion compound (SCF-E-ß-CD), liposome (SEL), and SCL of SCF-E to characterize the pharmacokinetic behaviors and liver targeting in rats. The ß-CD inclusion complex (SCF-E-ß-CD) was used to improve the solubility. The concentrations were determined using high-performance liquid chromatography (HPLC) and analyzed by DAS3.0. The pharmacokinetic results indicate that the plasma concentration-time courses were fitted well to the one-compartment model with the first weighing factor. The half-life period (t1/2) and area under the concentration-time curve (AUC) of the three components in SCL were the largest. The SCL exhibit a relatively high liver targeting effect. The results would be helpful for guiding the clinical application of this herbal medicine.

Safety and Toxicology of Magnolol and Honokiol.

Magnolia officinalis and Magnolia obovata bark extracts have been used for thousands of years in Chinese and Japanese traditional medicines and are still widely employed as herbal preparations for their sedative, antioxidant, anti-inflammatory, antibiotic, and antispastic effects. Neolignans, particularly magnolol and honokiol, are the main substances responsible for the beneficial properties of the magnolia bark extract (MBE). The content of magnolol and honokiol in MBE depends on different factors, including the Magnolia plant species, the area of origin, the part of the plant employed, and the method used to prepare the extract. The biological and pharmacological activities of magnolol and honokiol have been extensively investigated. Here we review the safety and toxicological properties of magnolol and honokiol as pure substances or as components of concentrated MBE, including the potential side-effects in humans after oral intake. In vitro and in vivo genotoxicity studies indicated that concentrated MBE has no mutagenic and genotoxic potential, while a subchronic study performed according to OECD (Organisation for Economic Co-operation and Development) guidelines established a no adverse effect level for concentrated MBE > 240 mg/kg b.w/d. Similar to other dietary polyphenols, magnolol and honokiol are subject to glucuronidation, and despite a relatively quick clearance, an interaction with pharmaceutical active principles or other herbal constituents cannot be excluded. However, intervention trials employing concentrated MBE for up to 1 y did not report adverse effects. In conclusion, over the recent years different food safety authorities evaluated magnolol and honokiol and considered them safe.

Effects of Dietary Supplementation of Astaxanthin and Sesamin on Daily Fatigue: A Randomized, Double-Blind, Placebo-Controlled, Two-Way Crossover Study.

Severe fatigue can negatively affect quality of life, and oxidative stress may play a role in its mechanism. The aim of this study was to evaluate the effect of dietary supplementation of astaxanthin and sesamin (AS), strong food-derived antioxidants, on fatigue. Twenty-four healthy volunteers were supplemented with AS and placebo, each for four weeks. After each supplementation period, participants underwent tasks inducing mental and physical fatigue (visual display terminal task and ergometer task, respectively). Subjective fatigue was evaluated using a visual analogue scale during and after the mental and physical tasks, and daily subjective fatigue was evaluated by the Chalder fatigue questionnaire. Secondary outcomes included other subjective feelings, work efficiency, autonomic nerve activity, levels of an oxidative stress marker (plasma phosphatidylcholine hydroperoxide (PCOOH)) and safety. AS supplementation was associated with significantly improved recovery from mental fatigue compared with placebo. Increased PCOOH levels during mental and physical tasks were attenuated by AS supplementation. No differences between AS and placebo were detected in secondary outcomes, and no adverse effects of AS supplementation were observed. In conclusion, AS supplementation may be a candidate to promote recovery from mental fatigue which is experienced by many healthy people.

Association between dietary phytoestrogens intakes and prostate cancer risk in Sicily.

OBJECTIVE: In this study we aimed to investigate the association between dietary phytoestrogen consumption and prostate cancer in a sample of southern Italian individuals. METHODS: A population-based case-control study on the association between prostate cancer and dietary factors was conducted from January 2015 to December 2016 in a single institution of the municipality of Catania, southern Italy (Registration number: 41/2015). A total of 118 histopathological-verified prostate cancer (PCa) cases and a total of 222 controls were collected. Dietary data was collected by using two food frequency questionnaires. RESULTS: Patients with PCa consumed significantly higher levels of phytoestrogens. Multivariate logistic regression showed that lignans (Q[quartile]4 vs. Q1, OR [odds ratio] = 4.72; p < .05) and specifically, lariciresinol (Q4 vs. Q1, OR = 4.60; p < .05), pinoresinol (Q4 vs. Q1, OR = 5.62; p < .05), matairesinol (Q4 vs. Q1, OR = 3.63; p < .05), secoisolariciresinol (Q4 vs. Q1, OR = 4.10; p < .05) were associated with increased risk of PCa. Furthermore, we found that isoflavones (Q3 vs. Q1, OR = 0.28; p < .05) and specifically, genistein (Q4 vs. Q1, OR = 0.40; p < .05) were associated with reduced risk of PCa. CONCLUSION: We found of an inverse association between dietary isoflavone intake and PCa, while a positive association was found with lignans intake.

Is there a potential of misuse for Magnolia officinalis compounds/metabolites?

OBJECTIVE: Magnolia bark contains magnolol, metabolized to tetrahydromagnolol and honokiol, with both GABA-ergic/cannabimimetic activities, hence of possible attraction to vulnerable individuals/recreational misusers. METHODS: A literature review, assessment of related anecdotal online Magnolia misuse's reports and an overview of Magnolia products' online acquisition possibilities has been here described. RESULTS: No peer-reviewed papers about Magnolia abuse/misuse/dependence/addiction were identified. Conversely, from a range of websites emerged potentially 3 groups of Magnolia misusers: (a) subjects with a psychiatric history already treated with benzodiazepines, being attracted to Magnolia bark as a "natural sedative"; (b) polydrug misusers, ingesting Magnolia with a range of other herbs/plants, attracted by the GABA-ergic/cannabimimetic activities; (c) subjects naive to the misusing drugs' scenario, perceiving Magnolia as a natural dietary supplement/weight-control compound. CONCLUSIONS: To the best of our knowledge, this is the first paper commenting on the possible Magnolia derivatives' potential of misuse. Magnolia's recent increase in popularity, mainly as a sedative, may be arguably due to its peculiar pharmacological properties/acceptable affordability levels/virtually worldwide favorable legal status and customers' attraction to a product being perceived as "natural" and hence somehow "safe." Future/potent/synthetic magnolol and honokiol structural analogues could however contribute to increasing the number of synthetic GABA-ergic/cannabimimetic misusing compounds.

Biochemical mechanism underlying hypertriglyceridemia and hepatic steatosis/hepatomegaly induced by acute schisandrin B treatment in mice.

BACKGROUND: It has been demonstrated that acute oral administration of schisandrin B (Sch B), an active dibenzocyclooctadiene isolated from Schisandrae Fructus (a commonly used traditional Chinese herb), increased serum and hepatic triglyceride (TG) levels and hepatic mass in mice. The present study aimed to investigate the biochemical mechanism underlying the Sch B-induced hypertriglyceridemia, hepatic steatosis and hepatomegaly. METHODS: Male ICR mice were given a single oral dose of Sch B (0.25-2 g/kg). Sch B-induced changes in serum levels of biomarkers, such as TG, total cholesterol (TC), apolipoprotein B48 (ApoB 48), very-low-density lipoprotein (VLDL), non-esterified fatty acid (NEFA) and hepatic growth factor (HGF), as well as hepatic lipids and mass, epididymal adipose tissue (EAT) and adipocyte size, and histological changes of the liver and EAT were examined over a period of 12-120 h after Sch B treatment. RESULTS: Serum and hepatic TG levels were increased by 1.0-4.3 fold and 40-158% at 12-72 h and 12-96 h, respectively, after Sch B administration. Sch B treatment elevated serum ApoB 48 level (up to 12%), a marker of exogenous TG, but not VLDL, as compared with the vehicle treatment. Treatment with Sch B caused a time-/dose-dependent reduction in EAT index (up to 39%) and adipocyte size (up to 67%) and elevation in serum NEFA level (up to 55%). Sch B treatment induced hepatic steatosis in a time-/dose-dependent manner, as indicated by increases in total vacuole area (up to 3.2 fold vs. the vehicle control) and lipid positive staining area (up to 17.5 × 103 µm2) in liver tissue. Hepatic index and serum HGF levels were increased by 18-60% and 42-71% at 12-120 h and 24-72 h post-Sch B dosing, respectively. In addition, ultrastructural changes, such as increase in size and disruption of cristae, in hepatic mitochondria were observed in Sch B-treated mice. CONCLUSION: Our findings suggest that exogenous sources of TG and the breakdown of fat storage in the body contribute to Sch B-induced hypertriglyceridemia and hepatic steatosis in mice. Hepatomegaly (a probable hepatotoxic action) caused by Sch B may result from the fat accumulation and mitochondrial damage in liver tissue.

Effect of Flaxseed Intervention on Inflammatory Marker C-Reactive Protein: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Functional food-flaxseed and its derivatives (flaxseed oil or lignans) are beneficial for human health, possibly because of their anti-inflammatory effects. C-reactive protein (CRP), a sensitive marker of inflammation was chosen to evaluate the anti-inflammatory effects of flaxseed. We searched randomized controlled trials from PubMed and the Cochrane Library in October 2015 and conducted a meta-analysis to evaluate the effectiveness of flaxseed and its derivatives on CRP. The mean differences (net change) in CRP (mg/L) concentrations were pooled with a random- or a fixed-effects model depending on the results of heterogeneity tests. Overall, flaxseed interventions had no effects on reduction of CRP (p = 0.428). The null effects were consistent in the subgroup analysis with multiple studies and population characteristics. Significant heterogeneity was observed in most of the analyses. Meta-regression identified baseline body mass index (BMI) as a significant source of heterogeneity (P-interaction = 0.032), with a significant reduction in CRP of 0.83 mg/L (95% confidence interval -1.34 to -0.31; p = 0.002) among subjects with a BMI of ≥30 kg/m². In conclusion, our meta-analysis did not find sufficient evidence that flaxseed and its derivatives have a beneficial effect on reducing circulating CRP. However, they may significantly reduce CRP in obese populations.

Comparative pharmacokinetics of purified flaxseed and associated mammalian lignans in male Wistar rats.

Consumption of flaxseed lignans is associated with various health benefits; however, little is known about the bioavailability of purified lignans in flaxseed. Data on their bioavailability and hence pharmacokinetics (PK) are necessary to better understand their role in putative health benefits. In the present study, we conducted a comparative PK analysis of the principal lignan of flaxseed, secoisolariciresinol diglucoside (SDG), and its primary metabolites, secoisolariciresinol (SECO), enterodiol (ED) and enterolactone (EL) in rats. Purified lignans were intravenously or orally administered to each male Wistar rat. SDG and its primary metabolites SECO, ED and EL were administered orally at doses of 40, 40, 10 and 10 mg/kg, respectively, and intravenously at doses of 20, 20, 5 and 1 mg/kg, respectively. Blood samples were collected at 0 (pre-dose), 5, 10, 15, 20, 30 and 45 min, and at 1, 2, 4, 6, 8, 12 and 24 h post-dosing, and serum samples were analysed. PK parameters and oral bioavailability of purified lignans were determined by non-compartmental methods. In general, administration of the flaxseed lignans SDG, SECO and ED demonstrated a high systemic clearance, a large volume of distribution and short half-lives, whereas administration of EL at the doses of 1 mg/kg (intravenously) and 10 mg/kg (orally administered) killed the rats within a few hours of dosing, precluding a PK analysis of this lignan. PK parameters of flaxseed lignans exhibited the following order: systemic clearance, SDG < SECO < ED; volume of distribution, SDG < SECO < ED; half-life, SDG < ED < SECO. The percentage of oral bioavailability was 0, 25 and < 1 % for SDG, SECO and ED, respectively.

Combined effects of urinary phytoestrogens metabolites and polymorphisms in metabolic enzyme gene on idiopathic male infertility.

Phytoestrogens are plant-derived compounds that may interact with estrogen receptors and mimic estrogenic effects. It remains unclear whether the individual variability in metabolizing phytoestrogens contributes to phytoestrogens-induced beneficial or detrimental effects. Our aim was to determine whether there is any interaction between metabolic rates (MR) of phytoestrogens and genetic polymorphisms in related xenobiotic metabolizing enzyme genes. MR was used to assess phytoestrogen exposure and individual metabolic ability. The amount of phytoestrogens in urine was measured by ultra-high performance liquid chromatography-tandem mass spectrometry in 600 idiopathic infertile male patients and 401 controls. Polymorphisms were genotyped using the SNPstream platform combined with the Taqman method. Prototypes and metabolites of secoisolariciresinol (SEC) have inverse effects on male reproduction. It was found that low MR of SEC increased the risk of male infertility (OR 2.49, 95 % CI 1.78, 3.48, P trend = 8.00 × 10(-8)). Novel interactions were also observed between the MR of SEC and rs1042389 in CYP2B6, rs1048943 in CYP1A1, and rs1799931 in NAT2 on male infertility (P inter = 1.06 × 10(-4), 1.14 × 10(-3), 3.55 × 10(-3), respectively). By analyzing the relationships between urinary phytoestrogen concentrations, their metabolites and male infertility, we found that individual variability in metabolizing SEC contributed to the interpersonal differences in SEC's effects on male reproduction.

Urinary phytoestrogen levels related to idiopathic male infertility in Chinese men.

Phytoestrogens (PEs) are naturally occurring chemical constituents of certain plants. The internal PE exposures, mainly from diet, vary among different populations and in different regions due to various eating habits. To investigate the potential relationship between urinary PE levels and idiopathic male infertility and semen quality in Chinese adult males, 608 idiopathic infertile men and 469 fertile controls were recruited by eligibility screening procedures. Individual exposure to PEs was measured using UPLC-MS/MS as spot urinary concentrations of 6 PEs (daidzein, DAI; equol, EQU; genistein, GEN; naringenin, NAR; coumestrol, COU; and secoisolariciresinol, SEC), which were adjusted with urinary creatinine (CR). Semen quality was assessed by sperm concentration, number per ejaculum and motility. We found that exposures to DAI, GEN and SEC were significantly associated with idiopathic male infertility (P-value for trend=0.036; 0.002; and 0.0001, respectively), while these exposures had stronger association with infertile subjects with at least one abnormal semen parameter than those with all normal semen parameters. Exposures to DAI, GEN and SEC were also related to idiopathic male infertility with abnormal sperm concentration, number per ejaculum and motility (P-value for trend<0.05), while these exposures had stronger association with the infertile men with abnormal sperm number per ejaculum. These findings provide the evidence that PE exposures are related to male reproductive function and raise a public health concern because that exposure to PEs is ubiquitous in China.

Hypospadias and maternal intake of phytoestrogens.

Experimental data indicate that gestational exposures to estrogenic compounds impact risk of hypospadias. We examined whether risk of hypospadias (i.e., a congenital malformation in which the opening of the penile urethra occurs on the ventral side of the penis) was associated with maternal intake of phytoestrogens, given their potential impact on estrogen metabolism. The analysis included data on mothers of 1,250 hypospadias cases and 3,118 controls who delivered their infants from 1997 to 2005 and participated in the National Birth Defects Prevention Study, a multistate, population-based, case-control study. After adjustment for several covariates, high intakes of daidzein, genistein, glycetin, secoisolariciresinol, total isoflavones, total lignans, and total phytoestrogens were associated with reduced risks; odds ratios comparing intakes ≥90th percentile with intakes between the 11th and 89th percentiles ranged from 0.6 to 0.8. For example, the odds ratio for total phytoestrogen intake was 0.7 (95% confidence interval: 0.5, 1.0). This study represents the first large-scale analysis of phytoestrogen intake and hypospadias. The observed associations merit investigation in additional populations before firm conclusions can be reached.

No evidence of hypoglycemia or hypotension in older adults during 6 months of flax lignan supplementation in a randomized controlled trial: a safety evaluation.

CONTEXT: The natural health product, BeneFlax, is a standardized flaxseed [Linum usitatissimum L. (Linaceae)] lignan enriched product with evidence of product quality and known quantity of the bioactive component, lignan. The acceptance of this natural health product for its various health benefits requires greater evidence of its safety in the general population. OBJECTIVE: We determined whether flaxseed lignan causes clinical hypoglycemia or hypotension in healthy older adults as an important aspect of safety. MATERIALS AND METHODS: Participants aged 49-87 years were randomized in a double-blind trial to receive flaxseed lignan (543 mg/day in BeneFlax) or placebo while completing a 6-month walking program. The 94 participants who completed the study were stratified by age (<65 years versus ≥65 years) and treatment category to determine whether older adults were more susceptible to adverse effects. RESULTS: After 6 months of treatment, average plasma glucose level (5.4 ± 0.6 mmol/L), systolic blood pressure (127 ± 14 mm Hg), and diastolic blood pressure (80 ± 9 mm Hg) were within normal clinical range. Controlling for sex and body mass index covariates resulted in no observed differences between plasma glucose or blood pressure measurements between treatment or age groups (p > 0.05). No incidents of hypoglycemia or hypotension were observed during BeneFlax treatment, suggesting that 543 mg falls at or below the no observable adverse effect level (NOAEL). DISCUSSION AND CONCLUSION: These data suggest the flaxseed lignan product BeneFlax does not pose a risk of hypoglycemia or hypotension in healthy adults aged 49-87 years.

Effects of abomasal infusion of flaxseed (Linum usitatissimum) oil on microbial ß-glucuronidase activity and concentration of the mammalian lignan enterolactone in ruminal fluid, plasma, urine and milk of dairy cows.

Ruminal microbiota plays an important role in the conversion of plant lignans into mammalian lignans. The main mammalian lignan present in the milk of dairy cows fed flax products is enterolactone (EL). The objectives of the present study were to investigate the effects of abomasal infusion of flax oil on the metabolism of flax lignans and concentrations of EL in biological fluids of dairy cows. A total of six rumen-cannulated dairy cows were assigned within a 2 × 3 factorial arrangement of six treatments utilising flax hulls (0 and 15·9 % of DM) and abomasal infusion of flax oil (0, 250 and 500 g/d). There were six periods of 21 d each. Samples were collected during the last 7 d of each period and subjected to chemical analysis. Flax hull supplementation increased concentrations of EL in ruminal fluid, plasma, urine and milk, while flax oil infusion had no effect. Post-feeding, ß-glucuronidase activity in the ruminal fluid of cows infused with 250 g flax oil was significantly lower for cows fed hulls than for those fed the control diet. The present study demonstrated that the presence of a rich source of n-3 fatty acids such as flax oil in the small intestine does not interfere with the absorption of the mammalian lignan EL and that lower ruminal ß-glucuronidase activity had no effect on the conversion of flax lignans into EL in the rumen of dairy cows.

Intake of phytoestrogen foods and supplements among women recently diagnosed with breast cancer in Ontario, Canada.

Phytoestrogens are found in foods such as soy (isoflavones) and flaxseed (lignans), and certain botanical supplements. Their role in estrogen receptor positive (ER+) breast cancer recurrence and treatment is controversial, and it is unknown how this affects intake among patients. The Ontario Cancer Registry was used to identify 417 population-based breast cancer cases (mean time from diagnosis was 57 days). A questionnaire was mailed to determine intake of phytoestrogen foods and supplements in the last 2 mo, changes since diagnosis and differences by ER tumor status or hormonal treatment. Of 278 (67%) respondents, 56% consumed soy foods, 39% consumed isoflavone-rich foods (tofu, soybeans, soy milk, soy nuts), and 70% ate lignan-rich foods, including flaxseed (33%). Only soy milk, flaxseed, and flaxseed bread were commonly consumed more than once/wk. Few patients (4%) took isoflavone (soy, red clover, kudzu, licorice, isoflavones) or lignan/flaxseed supplements. Since diagnosis, 17% started or stopped soy foods (most stopped); this was more prevalent among those receiving hormonal treatment (20%; 95% confidence interval (CI): 14, 26) than not (6%; 95% CI: 1, 12). No other differences by ER status or hormonal treatment were observed. Research is needed to confirm this and to explore influencing factors.

Phytoestrogen consumption and association with breast, prostate and colorectal cancer in EPIC Norfolk.

Phytoestrogens are polyphenolic secondary plant metabolites that have structural and functional similarities to 17beta-oestradiol and have been associated with a protective effect against hormone-related cancers. Most foods in the UK only contain small amounts of phytoestrogens (median content 21 microg/100 g) and the highest content is found in soya and soya-containing foods. The highest phytoestrogen content in commonly consumed foods is found in breads (average content 450 microg/100 g), the main source of isoflavones in the UK diet. The phytoestrogen consumption in cases and controls was considerably lower than in Asian countries. No significant associations between phytoestrogen intake and breast cancer risk in a nested case-control study in EPIC Norfolk were found. Conversely, colorectal cancer risk was inversely associated with enterolignan intake in women but not in men. Prostate cancer risk was positively associated with enterolignan intake, however this association became non-significant when adjusting for dairy intake, suggesting that enterolignans can act as a surrogate marker for dairy or calcium intake.

Breast, colorectal, and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition-Norfolk in relation to phytoestrogen intake derived from an improved database.

BACKGROUND: The characterization of phytoestrogen intake and cancer risk has been hindered by the absence of accurate dietary phytoestrogen values. OBJECTIVE: We examined the risk of breast, colorectal, and prostate cancers relative to phytoestrogen intake on the basis of a comprehensive database. DESIGN: Demographic and anthropometric characteristics, a medical history, and 7-d records of diet were collected prospectively from participants (aged 40-79 y) in the European Prospective Investigation into Cancer and Nutrition-Norfolk (EPIC-Norfolk). Five hundred nine food items were analyzed by liquid chromatography-mass spectrometry/mass spectrometry, and (13)C(3)-labeled internal standards were analyzed for isoflavones (genistein, daidzein, glycitein, biochanin A, and formononetin), lignans (secoisolariciresinol and matairesinol), and enterolignans from gut microbial metabolism in animal food sources (equol and enterolactone). From the direct analysis, values for 10,708 foods were calculated. Odds ratios (ORs) for breast (244 cases, 941 controls), colorectal (221 cases, 886 controls), and prostate (204 cases, 812 controls) cancers were calculated relative to phytoestrogen intake. RESULTS: Phytoestrogen intake was not associated with breast cancer among women or colorectal cancer among men. Among women, colorectal cancer risk was inversely associated with enterolactone (OR: 0.33; 95% CI: 0.14, 0.74) and total enterolignans (OR: 0.32; 95% CI: 0.13, 0.79), with a positive trend detected for secoisolariciresinol (OR: 1.60; 95% CI: 0.96, 2.69). A positive trend between enterolignan intake and prostate cancer risk (OR: 1.27; 95% CI: 0.97, 1.66) was attenuated after adjustment for dairy intake (OR: 1.19; 95% CI: 0.77, 1.82). CONCLUSION: Dietary phytoestrogens may contribute to the risk of colorectal cancer among women and prostate cancer among men.

A randomized controlled trial of the effects of flaxseed lignan complex on metabolic syndrome composite score and bone mineral in older adults.

A randomized double-blind placebo controlled study design was used to assess the effects of flaxseed lignan complex supplementation during exercise training on a metabolic syndrome composite score and osteoporosis risk in older adults. A total of 100 subjects (>or=50 years) were randomized to receive flaxseed lignan (543 mg.day-1 in a 4050 mg complex) or placebo while completing a 6 month walking program (30-60 min.day-1, 5-6 days.week-1). Fasting serum glucose, triacylglycerol (TAG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, total cholesterol, interleukin-6, and tumor necrosis factor-alpha were measured every 2 months, while body composition, bone mineral density, and resting blood pressure were assessed at baseline and at 6 months. A composite Z score of 6 risk factors for metabolic syndrome (fasting glucose, HDL cholesterol, TAG, abdominal adiposity, blood pressure, and inflammatory cytokines) was calculated at baseline and at 6 months. Men taking placebo increased metabolic syndrome composite Z score (p < 0.05), but there were no changes in the other groups. A significant group x sex x time interaction was noted for TAG (p = 0.017) and diastolic blood pressure (p = 0.046), with men taking flaxseed lignan decreasing diastolic blood pressure relative to men taking placebo, and men taking placebo increasing TAG relative to men taking flax lignan. There were no differences between groups for change in bone measures, body composition, lipoproteins, or cytokines. Males taking the flaxseed lignan complex reduced metabolic syndrome score relative to men taking placebo, but a similar trend was not seen in females. Flaxseed lignan had no effect on bone mineral density or content, body composition, lipoproteins, glucose, or inflammation.