28 June 2017 In General Health

Background: Hydroxytyrosol is a phenolic compound that is present in virgin olive oil (VOO) and wine. Hydroxytyrosol-related foods have been shown to protect against cardiovascular disease (CVD).

Objective: We investigated the associations between hydroxytyrosol and its biological metabolite, 3-O-methyl-hydroxytyrosol, also known as homovanillyl alcohol (HVAL), with CVD and total mortality.

Design: We included 1851 men and women with a mean +/- SD age of 66.8 +/- 6 y at high risk of CVD from prospective cohort data. The primary endpoint was a composite of myocardial infarction, stroke, and death from cardiovascular causes; the secondary endpoint was all-cause mortality. Twenty-four-hour urinary hydroxytyrosol and HVAL and catechol-O-methyltransferase (COMT) rs4680 genotypes were measured.

Results: After multivariable adjustment, all biomarkers were associated, as a continuous variable, with lower CVD risk, but only HVAL showed a strong inverse association (HR: 0.44; 95% CI: 0.25, 0.80) for the comparison between quintiles. Only HVAL, as a continuous variable, was associated with total mortality (HR: 0.81; 95% CI: 0.70, 0.95). Individuals in the highest quintile of HVAL compared with the lowest had 9.2 (95% CI: 3.5, 20.8) and 6.3 (95% CI: 2.3, 12.1) additional years of life or years free of CVD, respectively, after 65 y. Individuals with the rs4680GG genotype had the highest HVAL concentrations (P = 0.05). There was no association between COMT genotypes and events or interaction between COMT genotypes and HVAL concentrations.

Conclusions: We report, for the first time to our knowledge, an independent association between high urinary HVAL concentrations and a lower risk of CVD and total mortality in elderly individuals. VOO and wine consumption and a high metabolic COMT capacity for methylation are key factors for high HVAL concentrations. The association that stems from our results reinforces the benefits of 2 key components of the Mediterranean diet (wine and VOO). This trial was registered at www.predimed.es as ISRCTN35739639.

15 December 2016 In Cancer

BACKGROUND: Alcohol consumption is associated with increased risk of numerous cancers, but existing evidence for an association with melanoma is equivocal. No study has evaluated the association with different anatomic locations of melanoma.

METHODS: We used data from three large prospective cohort studies to investigate whether alcohol intake was associated with risk of melanoma. Alcohol intake was assessed repeatedly by food-frequency questionnaires. A Cox proportional hazards model was used to calculate multivariate-adjusted hazard ratios (HRs).

RESULTS: A total of 1,374 cases of invasive melanoma were documented during 3,855,706 person-years of follow-up. There was an association between higher alcohol intake and incidence of invasive melanoma (pooled multivariate HR 1.14 [95% confidence interval (CI), 1.00-1.29] per drink/day; Ptrend = 0.04). Among alcoholic beverages, white wine consumption was associated with an increased risk of melanoma (pooled multivariate HR 1.13 [95% CI, 1.04-1.24] per drink/day; Ptrend <0.01) after adjusting for other alcoholic beverages. The association between alcohol consumption and melanoma risk was stronger for melanoma in relatively UV-spared sites (trunk) versus more UV-exposed sites (head, neck, or extremities). Compared with nondrinkers, the pooled multivariate-adjusted HRs for >/=20 g/day of alcohol were 1.02 (95% CI, 0.64-1.62; Ptrend = 0.25) for melanomas of the head, neck, and extremities and 1.73 (95% CI, 1.25-2.38; Ptrend = 0.02) for melanomas of the trunk.

CONCLUSIONS: Alcohol intake was associated with a modest increase in the risk of melanoma, particularly in UV-protected sites. IMPACT: These findings further support American Cancer Society Guidelines for Cancer Prevention to limit alcohol intake. Cancer Epidemiol Biomarkers Prev; 25(12); 1550-8. (c)2016 AACR

21 September 2016 In General Health

BACKGROUND: High alcohol consumption is a major cause of morbidity, yet alcohol is associated with both favourable and adverse effects on cardiometabolic risk markers. We aimed to characterize the associations of usual alcohol consumption with a comprehensive systemic metabolite profile in young adults.

METHODS: Cross-sectional associations of alcohol intake with 86 metabolic measures were assessed for 9778 individuals from three population-based cohorts from Finland (age 24-45 years, 52% women). Metabolic changes associated with change in alcohol intake during 6-year follow-up were further examined for 1466 individuals. Alcohol intake was assessed by questionnaires. Circulating lipids, fatty acids and metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays.

RESULTS: Increased alcohol intake was associated with cardiometabolic risk markers across multiple metabolic pathways, including higher lipid concentrations in HDL subclasses and smaller LDL particle size, increased proportions of monounsaturated fatty acids and decreased proportion of omega-6 fatty acids, lower concentrations of glutamine and citrate (P < 0.001 for 56 metabolic measures). Many metabolic biomarkers displayed U-shaped associations with alcohol consumption. Results were coherent for men and women, consistent across the three cohorts and similar if adjusting for body mass index, smoking and physical activity. The metabolic changes accompanying change in alcohol intake during follow-up resembled the cross-sectional association pattern (R2 = 0.83, slope = 0.72 +/- 0.04).

CONCLUSIONS: Alcohol consumption is associated with a complex metabolic signature, including aberrations in multiple biomarkers for elevated cardiometabolic risk. The metabolic signature tracks with long-term changes in alcohol consumption. These results elucidate the double-edged effects of alcohol on cardiovascular risk.

02 August 2016 In Cancer

BACKGROUND: Alcohol increases the risk of breast cancer even at moderate levels of intake. However, the relationship between alcohol consumption and mortality among breast cancer patients is less clear.

METHODS: This study included women from the Women's Health Initiative observational study and randomized trial diagnosed with breast cancer (n = 7,835). Cox proportional hazards regression was used to estimate adjusted HRs and 95% confidence intervals (CI) for overall and breast cancer-specific (BCS) mortality associated with drinking alcohol before or after a breast cancer diagnosis. We also assessed whether changes in drinking habits after diagnosis are related to mortality.

RESULTS: Women who were consuming alcohol prior to their breast cancer diagnosis had a nonstatistically significant 24% (95% CI, 0.56-1.04) reduced risk of BCS mortality and a 26% (95% CI, 0.61-0.89) reduced risk of all-cause mortality. Some variation was observed by estrogen receptor (ER) status as alcohol consumption was associated with a 49% (95% CI, 0.31-0.83) reduced risk of BCS mortality among ER- patients with no change in risk observed among ER+ patients (HR = 0.97; 95% CI, 0.31-1.54), though the difference between these risks was not statistically significant (P for interaction = 0.39). Postdiagnosis alcohol consumption, and change in consumption patterns after diagnosis, did not appear to be associated with all-cause or BCS mortality.

CONCLUSION: In this large study, consumption of alcohol before or after breast cancer diagnosis did not increase risks of overall or cause-specific mortality.

IMPACT: Coupled with existing evidence, alcohol consumption is unlikely to have a substantial impact on mortality among breast cancer patients. Cancer Epidemiol Biomarkers Prev; 1-6. (c)2016 AACR.

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