Association between lignan polyphenol bioavailability and enterotypes of isoflavone metabolism: A cross-sectional analysis.

Lignan polyphenols derived from plants are metabolized by bacteria in the gut to mammalian lignans, such as enterolactone (ENL) and enterodiol (END). Mammalian lignan intake has been reported to be associated with obesity and low blood glucose levels. However, the factors that are responsible for individual differences in the metabolic capacity for ENL and END are not well understood. In the present study, the effects of enterotypes of isoflavone metabolism, equol producers (EQP) and O-desmethylangolensin producers (O-DMAP), on lignan metabolism were examined. EQP was defined by urinary daidzein (DAI) and equol concentrations as log(equol/DAI) ≥ -1.42. O-DMAP was defined by urinary DAI and O-DMA concentrations as O-DMA/DAI > 0.018. Isoflavone and lignan concentrations in urine samples from 440 Japanese women were measured by gas chromatography-mass spectrometry. Metabolic enterotypes were determined from the urinary equol and O-DMA concentrations. Urinary END and ENL concentrations were compared in four groups, combinations of EQP (+/-) and O-DMAP (+/-). The urinary lignan concentration was significantly higher in the O-DMAP/EQP group (ENL: P<0.001, END: P<0.001), and this association remained significant after adjusting for several background variables (END: ß = 0.138, P = 0.00607 for EQP and ß = 0.147, P = 0.00328 for O-DMAP; ENL: ß = 0.312, P<0.001 for EQP and ß = 0.210, P<0.001 for O-DMAP). The ENL/END ratio was also highest in the O-DMAP/EQP group, indicating that equol and O-DMA metabolizing gut bacteria may be involved in lignan metabolism. In conclusion, urinary lignan concentrations were significantly higher in groups containing either EQP or O-DMAP than in the non-EQP/non-O-DMAP group. The variables and participants in this study were limited, which the possibility of confounding by other variables cannot be ruled out. However, there are no established determinants of lignan metabolism to date. Further research is needed to determine what factors should be considered, and to examine in different settings to confirm the external validity.

Association between serum concentrations of perfluoroalkyl substances and global DNA methylation levels in peripheral blood leukocytes of Japanese women: A cross-sectional study.

Global DNA methylation levels in peripheral blood leukocytes can be a biomarker for cancer risk; however, levels can be changed by various factors such as environmental pollutants. We investigated the association between serum concentrations of perfluoroalkyl substances (PFASs) and global DNA methylation levels of leukocytes in a cross-sectional study using the control group of a Japanese breast cancer case-control study [397 women with a mean age of 54.1 (SD 10.1) years]. Importantly, our analysis distinguished branched PFAS isomers as different from linear isomers. The serum concentrations of 20 PFASs were measured by in-port arylation gas-chromatography negative chemical ionization mass spectrometry. Global DNA methylation levels in peripheral blood leukocytes were measured using a luminometric methylation assay. Associations between log10-transformed serum PFAS concentrations and global DNA methylation levels were evaluated by regression coefficients in multivariable robust linear regression analyses. Serum concentrations of 13 PFASs were significantly associated with increased global DNA methylation levels in leukocytes. Global DNA methylation was significantly increased by 1.45 %-3.96 % per log10-unit increase of serum PFAS concentration. Our results indicate that exposure to PFASs may increase global DNA methylation levels in peripheral blood leukocytes of Japanese women.

Urinary equol levels are positively associated with urinary estradiol excretion in women.

Isoflavones found in soy products are a promising class of nutrients that may have a positive effect on human health. In particular, the phytoestrogen metabolite equol is associated with a reduced risk of developing female hormone-related diseases. However, the effect of equol on estrogen remains unclear. Equol can modify blood and urinary estradiol (E2) levels. The aim of this cross-sectional study was to examine the associations between urinary estrogen levels, equol levels, and equol production status in Japanese women. We analyzed urine samples from 520 women by gas chromatography-mass spectrometry. Urinary E2 and 4-hydroxylated E2 levels were higher in equol producers (EQP) than in non-EQPs (P < 0.0001 and P=0.00112, respectively). After adjusting for age and tobacco use by analysis of covariance, the association remained significant (ß = 0.299, P < 0.0001). Analysis of covariance demonstrated that equol levels in urine were also positively associated with urinary E2 (ß = 0.597, P < 0.0001). The log equol concentration showed a significant, but moderate, negative association with the serum E2 concentration (ß = - 0.0225, P = 0.0462). Our findings suggest that equol may promote urinary E2 excretion and modify blood E2 levels in women.

Serum perfluoroalkyl substances and breast cancer risk in Japanese women: A case-control study.

BACKGROUND: Perfluoroalkyl substances (PFASs) may contribute to causing breast cancer; however, associations between exposure to PFASs and risk of breast cancer are controversial. OBJECTIVES: In the present study, we newly distinguished branched isomers of PFASs from their linear isomers and aimed to investigate the association between serum PFAS concentrations and breast cancer risk in Japanese women. METHODS: We used a case-control design to study 405 eligible matched pairs attending four hospitals in Nagano Prefecture, Japan from May 2001 to September 2005. We used in-port arylation gas-chromatography mass spectrometry with negative chemical ionization to measure serum concentrations of 20 PFAS congeners. We calculated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer and its hormone-receptor subtypes by quartiles or tertiles of serum PFASs. RESULTS: After multivariable adjustment for breast cancer risk factors, we found that serum concentrations of 20 PFAS congeners were significantly inversely associated with risk of breast cancer. Comparing the extreme quartiles of linear isomers of perfluorooctane sulfonate or perfluorooctanoic acid, ORs were 0.15 (95% CI: 0.07, 0.33 P for trend <0.0001) and 0.21 95% CI: 0.10, 0.44 P for trend <0.0001). Among postmenopausal women, whereas we found the linear isomer of perfluorotridecanoic acid to be inversely associated with breast cancer risk, a medium degree of exposure to the branched isomer of perfluorotridecanoic acid was associated with a marginally increased risk of breast cancer (OR [95% CI] = 1.74 [0.98, 3.09]). DISCUSSION: In our case-control study, we found overall no association between serum PFAS concentrations and increased risk of breast cancer. Many inverse associations between serum PFAS concentrations and breast cancer risk were found.