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

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

Effects of whole-grain wheat, rye, and lignan supplementation on cardiometabolic risk factors in men with metabolic syndrome: a randomized crossover trial.

BACKGROUND: A whole-grain (WG)-rich diet has shown to have potential for both prevention and treatment of the metabolic syndrome (MetS), which is a cluster of risk factors that increase the risk of type 2 diabetes and cardiovascular disease. Different WGs may have different health effects. WG rye, in particular, may improve glucose homeostasis and blood lipids, possibly mediated through fermentable dietary fiber and lignans. Recent studies have also suggested a crucial role of the gut microbiota in response to WG. OBJECTIVES: The aim was to investigate WG rye, alone and with lignan supplements [secoisolariciresinol diglucoside (SDG)], and WG wheat diets on glucose tolerance [oral-glucose-tolerance test (OGTT)], other cardiometabolic outcomes, enterolignans, and microbiota composition. Moreover, we exploratively evaluated the role of gut microbiota enterotypes in response to intervention diets. METHODS: Forty men with MetS risk profile were randomly assigned to WG diets in an 8-wk crossover study. The rye diet was supplemented with 280 mg SDG at weeks 4-8. Effects of treatment were evaluated by mixed-effects modeling, and effects on microbiota composition and the role of gut microbiota as a predictor of response to treatment were analyzed by random forest plots. RESULTS: The WG rye diet (± SDG supplements) did not affect the OGTT compared with WG wheat. Total and LDL cholesterol were lowered (-0.06 and -0.09 mmol/L, respectively; P < 0.05) after WG rye compared with WG wheat after 4 wk but not after 8 wk. WG rye resulted in higher abundance of Bifidobacterium [fold-change (FC) = 2.58, P < 0.001] compared with baseline and lower abundance of Clostridium genus compared with WG wheat (FC = 0.54, P = 0.02). The explorative analyses suggest that baseline enterotype is associated with total and LDL-cholesterol response to diet. CONCLUSIONS: WG rye, alone or with SDG supplementation, compared with WG wheat did not affect glucose metabolism but caused transient LDL-cholesterol reduction. The effect of WG diets appeared to differ according to enterotype. This trial was registered at www.clinicaltrials.gov as NCT02987595.

Comparative Nutrient Profiling of Retail Goat and Cow Milk.

Goat milk is globally consumed but nutritional profiling at retail level is scarce. This study compared the nutrient composition of retail cow and goat milk (basic solids, fatty acids, minerals, and phytoestrogens) throughout the year and quantified the potential implications on the consumers' nutrient intakes. When compared to cow milk, goat milk demonstrated nutritionally desirable traits, such as lower concentrations of C12:0, C14:0, C16:0 and Na: K ratio, and the higher concentrations of cis polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), isoflavones, B, Cu, Mg, Mn, P and I, although the latter may be less desirable in cases of high milk intakes. However, in contrast with nutritional targets, it had lower concentrations of omega-3 PUFA, vaccenic acid, lignans, Ca, S and Zn. The extent of these differences was strongly influenced by season and may demonstrate a combination of differences on intrinsic species metabolism, and farm breeding/husbandry practices.

Concentrations of phytoestrogens in conventional, organic and free-range retail milk in England.

The effect of dairy management system (conventional, CNV; organic, ORG; free-range, FRG) and month on retail milk phytoestrogen composition was assessed for 12 consecutive months. ORG milk contained more secoisolariciresinol, matairesinol, lariciresinol, sum of plant lignans, daidzein, genistein, formononetin, naringenin, equol, sum of isoflavones and coumestrol, than CNV and FRG milk. This may be explained by the higher supply of pasture, and grazed or ensiled clover, in ORG dairy diets. Seasonal variation in milk phytoestrogen concentrations was higher for ORG than CNV and FRG systems. Phytoestrogen composition did not vary between FRG and CNV milk. Consuming organic milk can increase intake of potentially beneficial lignans and isoflavonoids, and in particular equol; but, any effects on human health from such milk compositional differences cannot be implied.

Pre-diagnostic plasma enterolactone concentrations and breast cancer prognosis among postmenopausal women - The Danish Diet, Cancer and Health cohort.

BACKGROUND & AIMS: High intakes of the phytoestrogen lignans and high blood concentrations of its main biomarker, enterolactone, has been associated with a better breast cancer prognosis. We investigated the association between pre-diagnostic plasma concentrations of enterolactone and breast cancer prognosis (i.e. recurrence, breast cancer-specific mortality and all-cause mortality). METHODS: Plasma and data was available from the Danish Diet, Cancer and Health cohort. Information on treatment and clinical characteristics from registries and clinical databases and both pre-diagnostic and diagnostic plasma measurement of enterolactone on a sub-set. Enterolactone was quantified in plasma using a high-throughput LC-MS/MS method. We followed 1457 breast cancer cases from date of diagnosis and until censoring or end-of-follow-up (median 9 years), during this time 404 died (250 of breast cancer) and 267 experienced recurrence. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Plasma enterolactone were borderline significantly associated with lower breast cancer-specific mortality (HRdoubling = 0.93, 95% CI:0.86, 1.00, P = 0.0501), but not associated with all-cause mortality (HRdoubling = 0.95, 95% CI:0.89, 1.01) and recurrence (HRdoubling = 0.96, 95% CI: 0.89, 1.04) in the models adjusted for smoking, schooling, BMI, physical activity and use of menopausal hormones. Adjusting further for clinical characteristics and treatment did not change the results considerably. In the sensitivity analyses, an inverse association was found with all-cause and breast cancer-specific mortality for those where blood was collected ≤5 years before diagnosis. CONCLUSIONS: Overall, no clear association was found between pre-diagnostic plasma concentrations of enterolactone and breast cancer prognosis.

A Combination of Coffee Compounds Shows Insulin-Sensitizing and Hepatoprotective Effects in a Rat Model of Diet-Induced Metabolic Syndrome.

Since coffee may help to prevent the development of metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. In this study, 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high-fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control, but improved fed hyperinsulinemia (mean difference = 30.80 mU/L, p = 0.044) and homeostatic model assessment-insulin resistance (HOMA-IR) (mean difference = 15.29, p = 0.033), and plasma adiponectin levels (mean difference = -0.99 µg/mL, p = 0.048). The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating (mean difference = 4.75 U/L, p = 0.014) and intrahepatocellular alanine transaminase activity was assessed by hyperpolarized-13C nuclear magnetic resonance NMR spectroscopy and found to be reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.

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.

Targeted LC-MS/MS Method for the Quantitation of Plant Lignans and Enterolignans in Biofluids from Humans and Pigs.

Lignans have gained nutritional interest due to their promising role in the prevention of lifestyle diseases. However, epidemiological studies are in need of more evidence to link the intake of lignans to this promising role. In this context, it is necessary to study large population groups to obtain sufficient statistical power. Therefore, there is a demand for fast, sensitive, and accurate methods for quantitation with high throughput of samples. This paper presents a validated LC-MS/MS method for the quantitation of eight plant lignans (matairesinol, hydroxymatairesinol, secoisolariciresinol, lariciresinol, isolariciresinol, syringaresinol, medioresinol, and pinoresinol) and two enterolignans (enterodiol and enterolactone) in both human and pig plasma and urine. The method showed high selectivity and sensitivity allowing quantitation of lignans in the range of 0.024-100 ng/mL and with a run time of only 4.8 min per sample. The method was successfully applied to quantitate lignans in biofluids from ongoing studies with humans and pigs.