15 June 2015 In Phenolic compounds

SCOPE: Grape seed polyphenol extract (GSPE) is receiving increasing attention for its potential preventative and therapeutic roles in Alzheimer's disease (AD) and other age-related neurodegenerative disorders. The intestinal microbiota is known to actively convert many dietary polyphenols, including GSPE, to phenolic acids. There is limited information on the bioavailability and bioactivity of GSPE-derived phenolic acid in the brain.

METHODS AND RESULTS: We orally administered GSPE to rats and investigated the bioavailability of 12 phenolic acids known to be generated by microbiota metabolism of anthocyanidins. GSPE treatment significantly increased the content of two of the phenolic acids in the brain: 3-hydroxybenzoic acid and 3-(3 -hydroxyphenyl)propionic acid, resulting in the brain accumulations of the two phenolic acids at micromolar concentrations. We also provided evidence that 3-hydroxybenzoic acid and 3-(3 -hydroxyphenyl)propionic acid potently interfere with the assembly of beta-amyloid peptides into neurotoxic beta-amyloid aggregates that play key roles in AD pathogenesis.

CONCLUSION: Our observation suggests important contribution of the intestinal microbiota to the protective activities of GSPE (as well as other polyphenol preparations) in AD. Outcomes from our studies support future preclinical and clinical investigations exploring the potential contributions of the intestinal microbiota in protecting against the onset/progression of AD and other neurodegenerative conditions.

23 January 2015 In Cancer

OBJECTIVES: To investigate the role of factors that modulate the association between alcohol and mortality, and to provide estimates of absolute risk of death. DESIGN: The European Prospective Investigation into Cancer and nutrition (EPIC).

SETTING: 23 centres in 10 countries.

PARTICIPANTS: 380 395 men and women, free of cancer, diabetes, heart attack or stroke at enrolment, followed up for 12.6 years on average.

MAIN OUTCOME MEASURES: 20 453 fatal events, of which 2053 alcohol-related cancers (ARC, including cancers of upper aerodigestive tract, liver, colorectal and female breast), 4187 cardiovascular diseases/coronary heart disease (CVD/CHD), 856 violent deaths and injuries. Lifetime alcohol use was assessed at recruitment.

RESULTS: HRs comparing extreme drinkers (>/=30 g/day in women and >/=60 g/day in men) to moderate drinkers (0.1-4.9 g/day) were 1.27 (95% CI 1.13 to 1.43) in women and 1.53 (1.39 to 1.68) in men. Strong associations were observed for ARC mortality, in men particularly, and for violent deaths and injuries, in men only. No associations were observed for CVD/CHD mortality among drinkers, whereby HRs were higher in never compared to moderate drinkers. Overall mortality seemed to be more strongly related to beer than wine use, particularly in men. The 10-year risks of overall death for women aged 60 years, drinking more than 30 g/day was 5% and 7%, for never and current smokers, respectively. Corresponding figures in men consuming more than 60 g/day were 11% and 18%, in never and current smokers, respectively. In competing risks analyses, mortality due to CVD/CHD was more pronounced than ARC in men, while CVD/CHD and ARC mortality were of similar magnitude in women.

CONCLUSIONS: In this large European cohort, alcohol use was positively associated with overall mortality, ARC and violent death and injuries, but marginally to CVD/CHD. Absolute risks of death observed in EPIC suggest that alcohol is an important determinant of total mortality.

23 January 2015 In Cancer

BACKGROUND: Evidence for an association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarized the published evidence and evaluated the association using individual patient data from multiple case cohorts.

METHODS: A MEDLINE search to identify studies published up to January 2013 was performed. We combined published estimates of survival time for "moderate drinkers" versus nondrinkers. An analysis of individual participant data using Cox regression was carried out using data from 11 case cohorts.

RESULTS: We identified 11 published studies suitable for inclusion in the meta-analysis. Moderate postdiagnosis alcohol consumption was not associated with overall survival [HR, 0.95; 95% confidence interval (CI), 0.85-1.05], but there was some evidence of better survival associated with prediagnosis consumption (HR, 0.80; 95% CI, 0.73-0.88). Individual data on alcohol consumption for 29,239 cases with 4,839 deaths were available from the 11 case cohorts, all of which had data on estrogen receptor (ER) status. For women with ER-positive disease, there was little evidence that pre- or postdiagnosis alcohol consumption is associated with breast cancer-specific mortality, with some evidence of a negative association with all-cause mortality. On the basis of a single study, moderate postdiagnosis alcohol intake was associated with a small reduction in breast cancer-specific mortality for women with ER-negative disease. There was no association with prediagnosis intake for women with ER-negative disease.

CONCLUSION: There was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer-specific mortality for women with ER-positive disease. There was weak evidence that moderate post-diagnosis alcohol intake is associated with a small reduction in breast cancer-specific mortality in ER-negative disease.

IMPACT: Considering the totality of the evidence, moderate postdiagnosis alcohol consumption is unlikely to have a major adverse effect on the survival of women with breast cancer.

23 January 2015 In Cancer

OBJECTIVES: Results from studies examining the association between alcohol consumption and the risk of Barrett's esophagus have been inconsistent. We assessed the risk of Barrett's esophagus associated with total and beverage-specific alcohol consumption by pooling individual participant data from five case-control studies participating in the international Barrett's and Esophageal Adenocarcinoma Consortium.

METHODS: For analysis, there were 1,282 population-based controls, 1,418 controls with gastroesophageal reflux disease (GERD), and 1,169 patients with Barrett's esophagus (cases). We estimated study-specific odds ratios (ORs) and 95% confidence intervals (95% CI) using multivariable logistic regression models adjusted for age, sex, body mass index (BMI), education, smoking status, and GERD symptoms. Summary risk estimates were obtained by random-effects models. We also examined potential effect modification by sex, BMI, GERD symptoms, and cigarette smoking.

RESULTS: For comparisons with population-based controls, although there was a borderline statistically significant inverse association between any alcohol consumption and the risk of Barrett's esophagus (any vs. none, summary OR=0.77, 95% CI=0.60-1.00), risk did not decrease in a dose-response manner (Ptrend=0.72). Among alcohol types, wine was associated with a moderately reduced risk of Barrett's esophagus (any vs. none, OR=0.71, 95% CI=0.52-0.98); however, there was no consistent dose-response relationship (Ptrend=0.21). We found no association with alcohol consumption when cases were compared with GERD controls. Similar associations were observed across all strata of BMI, GERD symptoms, and cigarette smoking.

CONCLUSIONS: Consistent with findings for esophageal adenocarcinoma, we found no evidence that alcohol consumption increases the risk of Barrett's esophagus.

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