Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis.

BACKGROUND: Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns. METHODS: We meta-analysed epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates. Significant results of the meta-analysis were subsequently evaluated in gene set enrichment analysis (GSEA) and expression quantitative trait methylation (eQTM) analysis. RESULTS: In meta-analysis, methylation at 4,656 CpG sites was significantly associated with vitamin C intake at FDR ≤ 0.05. The most significant CpG sites associated with vitamin C (at FDR ≤ 0.01) were enriched for pathways associated with systems development and cell signalling in GSEA, and were associated with downstream expression of genes enriched in the immune response in eQTM analysis. Furthermore, methylation at 160 CpG sites was significantly associated with vitamin E intake at FDR ≤ 0.05, but GSEA and eQTM analysis of the top most significant CpG sites associated with vitamin E did not identify significant enrichment of any biological pathways investigated. CONCLUSIONS: We identified significant associations of many CpG sites with vitamin C and E intake, and our results suggest that vitamin C intake may be associated with systems development and the immune response.

Pooled analysis of epigenome-wide association studies of food consumption in KORA, TwinsUK and LLS.

PURPOSE: Examining epigenetic patterns is a crucial step in identifying molecular changes of disease pathophysiology, with DNA methylation as the most accessible epigenetic measure. Diet is suggested to affect metabolism and health via epigenetic modifications. Thus, our aim was to explore the association between food consumption and DNA methylation. METHODS: Epigenome-wide association studies were conducted in three cohorts: KORA FF4, TwinsUK, and Leiden Longevity Study, and 37 dietary exposures were evaluated. Food group definition was harmonized across the three cohorts. DNA methylation was measured using Infinium MethylationEPIC BeadChip in KORA and Infinium HumanMethylation450 BeadChip in the Leiden study and the TwinsUK study. Overall, data from 2293 middle-aged men and women were included. A fixed-effects meta-analysis pooled study-specific estimates. The significance threshold was set at 0.05 for false-discovery rate-adjusted p values per food group. RESULTS: We identified significant associations between the methylation level of CpG sites and the consumption of onions and garlic (2), nuts and seeds (18), milk (1), cream (11), plant oils (4), butter (13), and alcoholic beverages (27). The signals targeted genes of metabolic health relevance, for example, GLI1, RPTOR, and DIO1, among others. CONCLUSION: This EWAS is unique with its focus on food groups that are part of a Western diet. Significant findings were mostly related to food groups with a high-fat content.

Significant Impact of Coffee Consumption on MR-Based Measures of Cardiac Function in a Population-Based Cohort Study without Manifest Cardiovascular Disease.

Subclinical effects of coffee consumption (CC) with regard to metabolic, cardiac, and neurological complications were evaluated using a whole-body magnetic resonance imaging (MRI) protocol. A blended approach was used to estimate habitual CC in a population-based study cohort without a history of cardiovascular disease. Associations of CC with MRI markers of gray matter volume, white matter hyperintensities, cerebral microhemorrhages, total and visceral adipose tissue (VAT), hepatic proton density fat fraction, early/late diastolic filling rate, end-diastolic/-systolic and stroke volume, ejection fraction, peak ejection rate, and myocardial mass were evaluated by linear regression. In our analysis with 132 women and 168 men, CC was positively associated with MR-based cardiac function parameters including late diastolic filling rate, stroke volume (p < 0.01 each), and ejection fraction (p < 0.05) when adjusting for age, sex, smoking, hypertension, diabetes, Low-density lipoprotein (LDL), triglycerides, cholesterol, and alcohol consumption. CC was inversely associated with VAT independent of demographic variables and cardiovascular risk factors (p < 0.05), but this association did not remain significant after additional adjustment for alcohol consumption. CC was not significantly associated with potential neurodegeneration. We found a significant positive and independent association between CC and MRI-based systolic and diastolic cardiac function. CC was also inversely associated with VAT but not independent of alcohol consumption.

Role of Vitamin D in Preventing and Treating Selected Extraskeletal Diseases-An Umbrella Review.

Evidence is accumulating that vitamin D may have beneficial effects on respiratory tract, autoimmune, neuro-degenerative, and mental diseases. The present umbrella review of systematic reviews (SRs) of cohort studies and randomised controlled trials (RCTs), plus single Mendelian randomisation studies aims to update current knowledge on the potential role of vitamin D in preventing and treating these extraskeletal diseases. Altogether, 73 SRs were identified. Observational data on primary prevention suggest an inverse association between vitamin D status and the risk of acute respiratory tract infections (ARI), dementia and cognitive decline, and depression, whereas studies regarding asthma, multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM) are scarce. SRs of RCTs support observational data only for the risk of ARI. No respective RCTs are available for the prevention of chronic obstructive pulmonary disease (COPD), MS, and T1DM. SRs of RCTs indicate beneficial therapeutic effects in vitamin D-deficient patients with asthma and COPD, while effects on major depression and T1DM need to be further elucidated. Mendelian randomisation studies do not consistently support the results of SRs. Since several limitations of the included SRs and existing RCTs do not permit definitive conclusions regarding vitamin D and the selected diseases, further high-quality RCTs are warranted.

Long-term outcomes in patients with severe depression after in-hospital treatment - study protocol of the depression long-term Augsburg (DELTA) study.

INTRODUCTION: Depressive disorders are very common diseases entailing a great burden on affected people. However, comprehensive information on long-term disease course in patients with severe depression is lacking so far. The objectives of the DELTA study are to examine long-term outcomes and their predicting factors, to assess clinical response of antidepressant pharmacotherapy by applying therapeutic drug monitoring, to identify predictors of therapeutic non-response, to describe the long-term healthcare utilisation and to investigate the role of biomarkers in disease course. METHODS AND ANALYSIS: A cohort study including all adult hospitalised cases (age range 18 to 75 years) of severe major depression who are admitted to the Bezirkskrankenhaus Augsburg is established. It is planned to include 300 patients. During the hospital stay, information is gathered through personal interview, self-administered questionnaires, cognitive tests and chart review. Furthermore, biomaterials are collected. After hospital discharge, patients are repeatedly re-examined over time (3, 6, 12, 24 and 36 months) to collect information about mortality, relapse, depression severity, health-related quality of life (HRQOL), perceived stigma, cognitive functions, diet, physical activity, treatment and healthcare utilisation. Follow-up blood samples are collected to determine therapeutic drug levels. The primary study aim is to investigate long-term therapeutic response, survival, relapse, HRQOL and cognitive functions. Survival time and time to relapse or re-hospitalisation will be analysed using Cox regression models. Changes of HRQOL, depressive symptoms and cognitive functions over time will be examined using generalised linear regression models for repeated measures or mixed models. Correlates of the disease course will be modelled using suitable generalised linear, mixed, estimating equation and growth curve models. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Ludwig-Maximilians-Universität München (date of approval: 23 October 2017, reference number: 17-625). Study results will be presented at scientific conferences and published in peer-reviewed scientific journals.

Selenium and Prostate Cancer: Analysis of Individual Participant Data From Fifteen Prospective Studies.

BACKGROUND: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade. METHODS: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided. RESULTS: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, Pheterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, Ptrend < .001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, Pheterogeneity = .08). CONCLUSIONS: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation.

Associations between calcium and vitamin D supplement use as well as their serum concentrations and subclinical cardiovascular disease phenotypes.

BACKGROUND: Supplementation of calcium (Ca) and vitamin D for the prevention of osteoporosis is frequently found in Western countries. Recent re-analyses of clinical trials observed a higher risk of myocardial infarction and stroke in subjects taking Ca (+vitamin D) supplements, although the underlying mechanisms are not clear. OBJECTIVE: Thus, we analyzed the associations between Ca and vitamin D supplementation as well as serum concentrations of Ca and 25-hydroxyvitamin D (25(OH)D) and subclinical cardiovascular disease (CVD) phenotypes, namely intima-media thickness, ankle-brachial-index (ABI), intermittent claudication, and atrial fibrillation (AF). DESIGN: Data of 1601 participants aged 50-81 years of the population-based cross-sectional Cooperative Health Research in the Region of Augsburg (KORA) F4 study in Germany were analyzed. Logistic and linear regression models were used to estimate odds ratios (OR) (95% confidence intervals (CI)) and ß-estimates (p-values), respectively. RESULTS: Regular Ca supplementation showed a significant positive association with the presence of AF after multivariable adjustment (OR = 3.89; 95% CI 1.28-11.81). Higher serum 25(OH)D concentrations were independently associated with a lower prevalence of asymptomatic peripheral arterial disease as assessed by ABI measurements (ß = 0.007; p = 0.01). No other significant associations between supplementation or serum concentrations of Ca or vitamin D and CVD phenotypes were identified. CONCLUSIONS: Although based on few cases the finding of a significant higher prevalence of AF in Ca supplement users hints at one possible mechanism that may contribute to an increased risk of myocardial infarction and stroke. The observed association between serum 25(OH)D and ABI supports results from other studies.

Influence of external, intrinsic and individual behaviour variables on serum 25(OH)D in a German survey.

The objective of the present study was to identify external, intrinsic or behavioural factors that significantly influenced serum 25-hydroxyvitamin D (25(OH)D) concentrations in a German survey. Data from 3061 participants in the Cooperative Health Research in the Region of Augsburg, Germany (KORA) F4 survey were used to relate potential determinants to measured mean serum 25(OH)D concentrations using multivariable regression models. The factors significantly associated with hypovitaminosis D (defined as 25(OH)D<25 nmolL(-1)) were season (winter, spring and autumn), urban environment and high body mass index. In contrast, times spent in sunny regions, hours per day spent outdoors in the summer as well as additional oral intake were associated with higher 25(OH)D concentrations. These results suggest that mainly ambient UV exposure but also individual behaviour are the most important determinants for personal 25(OH)D concentrations. The analyses further showed that in winter 43% of subjects were vitamin D deficient and 42% insufficient. Even in summer over half the population has insufficient vitamin D status with 8% deficient and 47% insufficient. Therefore measures to mitigate widespread vitamin D insufficiency such as regular short-term sun exposure and/or improved dietary intake/supplementation recommendations by public health bodies need to be considered.

The association between urinary phytoestrogen excretion and components of the metabolic syndrome in NHANES.

BACKGROUND: Metabolic syndrome is a major risk factor for cardiovascular diseases, which are still the major cause of death in developed countries. METHODS: We cross-sectionally studied the association between urinary phytoestrogen excretion and metabolic cardiovascular risk factors. Hence, we used data from the National Health and Nutrition Examination Survey from 1999 to 2004 with 1,748 participants, who had urine levels of isoflavones and lignans measured. Geometric means of waist circumference, blood pressure, fasting glucose, HDL cholesterol, and triglyceride levels were computed by quartiles of isoflavone or lignan urinary excretion. Outcome was assessed as the presence of metabolic syndrome according to NCEP-ATP III criteria. The association between phytoestrogen concentration and the metabolic syndrome was calculated using logistic regression analyses. RESULTS: Plasma triglyceride and HDL cholesterol levels were lower in participants in the highest quartile of lignan excretion compared with the lowest (both P < 0.01). However, blood pressure, waist circumference, and plasma glucose levels did not differ significantly between extreme quartiles. The presence of metabolic syndrome was lower with increasing levels of urinary lignans (OR 0.48, 95% CI 0.28; 0.80 top vs. bottom quartile), especially when separately computed for the excretion of enterolactone (OR 0.47, 95% CI 0.28; 0.78). There was no significant association between isoflavone excretion and any component of the metabolic syndrome. CONCLUSIONS: Our study shows that an increasing excretion of lignans, especially enterolactone, might be associated with a decreased presence of the metabolic syndrome.

Urinary phytoestrogen levels and frailty in older American women of the National Health and Nutrition Examination Survey (NHANES) 1999-2002: a cross-sectional study.

BACKGROUND/AIMS: A deficit of various hormones during the process of aging and/or a heightened inflammatory state may be causally linked to the development of frailty. Phytoestrogens as weak estrogens, antioxidants, and anti-inflammatory agents may counteract this process. METHODS: In a cross-sectional study including two cycles of the National Health and Nutrition Examination Survey (NHANES, i.e. 1999-2002), logistic regression was used to analyze the association between urinary concentrations of isoflavones and lignans and frailty in 600 females aged 50 years or older (median age 66.5 years). Participants were classified as 'frail' (meeting 3 or more of the 5 frailty criteria), 'prefrail' (meeting 1 or 2 of the criteria), or 'robust' (meeting none of the criteria). Four percent were frail. RESULTS: For all of the phytoestrogens considered, the unadjusted OR were lower than 1 but generally not statistically significant aside from the association with O-desmethylangolensin (O-DMA) (OR = 0.76; 95% CI 0.61-0.92). Multivariate analysis did not attenuate this finding (OR = 0.74; 95% CI 0.61-0.90). CONCLUSIONS: This first analysis of the relationship between phytoestrogens and frailty revealed an inverse association between urinary O-DMA levels and frailty in women. However, the number of frail women was low. Although this finding may be confounded or biased, it seems worthwhile to intensify research on the potential preventive effects of O-DMA.

Association of urinary phytoestrogen concentrations with serum concentrations of prostate-specific antigen in the National Health and Nutrition Examination Survey.

Some clinical trials have shown that high phytoestrogen intake may decrease serum concentrations of prostate-specific antigen (PSA), and phytoestrogens may also lower prostate cancer risk. It was the aim of this study to examine the relationship between the serum PSA level and urine phytoestrogen concentration in generally healthy U.S. men. Eight hundred twenty-four men, 40+ yr old without prostate cancer, who participated in the 2001-2004 NHANES surveys, were included in the analysis. The association of total PSA, free PSA, and PSA ratio [free PSA/total PSA * 100] with concentrations of isoflavones and lignans (standardized for urinary creatinine concentration) was examined using multivariable-adjusted linear and logistic regression models. The linear regression analyses showed no clear association between creatinine-standardized urinary phytoestrogen concentrations and serum total or free PSA levels or PSA ratio. However, the odds of having a PSA ratio <15% rose from Quartile 1 to Quartile 4 of isoflavone excretion (odds ratio = 2.82, 95% confidence interval 1.28-6.22 for top vs. bottom quartile), but there were no associations with having a PSA ratio <25%. In generally healthy U.S. men, 40+ yr old without a diagnosis of prostate cancer, urinary isoflavone, and lignan concentrations were not associated with serum PSA level.

Calcium intake and serum concentration in relation to risk of cardiovascular death in NHANES III.

BACKGROUND: Evidence for an association between calcium intake and risk of cardiovascular death remains controversial. By assessing dietary intake, use of supplements, and serum levels of calcium, we aimed to disentangle this link in the third National Health and Nutrition Examination Survey (NHANES III). METHODS: Mortality linkage of NHANES III to death certificate data for those aged 17 years or older (n = 20,024) was used to estimate risk of overall cardiovascular death as well as death from ischemic heart disease (IHD), acute myocardial infarction (AMI), heart failure (HF), and cerebrovascular disease (CD) with multivariate Cox proportional hazards regression analysis. RESULTS: About 10.0% of the population died of cardiovascular disease and the majority (5.4%) died of IHD. There was increased risk of overall CVD death for those in the bottom 5% of serum calcium compared to those in the mid 90% (HR: 1.51 (95% CI: 1.03-2.22)). For women there was a statistically significant increased risk of IHD death for those with serum calcium levels in the top 5% compared to those in the mid 90% (HR: 1.72 (95%CI: 1.13-2.61)), whereas in men, low serum calcium was related to increased IHD mortality (HR: 2.32 (95% CI 1.14-3.01), Pinteraction: 0.306). No clear association with CVD death was observed for dietary or supplemental calcium intake. CONCLUSIONS: Calcium as assessed by serum concentrations is involved in cardiovascular health, though differential effects by sex may exist. No clear evidence was found for an association between dietary or supplementary intake of calcium and cardiovascular death.

Polymorphisms in thioredoxin reductase and selenoprotein K genes and selenium status modulate risk of prostate cancer.

Increased dietary intake of Selenium (Se) has been suggested to lower prostate cancer mortality, but supplementation trials have produced conflicting results. Se is incorporated into 25 selenoproteins. The aim of this work was to assess whether risk of prostate cancer is affected by genetic variants in genes coding for selenoproteins, either alone or in combination with Se status. 248 cases and 492 controls from an EPIC-Heidelberg nested case-control study were subjected to two-stage genotyping with an initial screening phase in which 384 tagging-SNPs covering 72 Se-related genes were determined in 94 cases and 94 controls using the Illumina Goldengate methodology. This analysis was followed by a second phase in which genotyping for candidate SNPs identified in the first phase was carried out in the full study using Sequenom. Risk of high-grade or advanced stage prostate cancer was modified by interactions between serum markers of Se status and genotypes for rs9880056 in SELK, rs9605030 and rs9605031 in TXNRD2, and rs7310505 in TXNRD1. No significant effects of SNPs on prostate cancer risk were observed when grade or Se status was not taken into account. In conclusion, the risk of high-grade or advanced-stage prostate cancer is significantly altered by a combination of genotype for SNPs in selenoprotein genes and Se status. The findings contribute to explaining the biological effects of selenium intake and genetic factors in prostate cancer development and highlight potential roles of thioredoxin reductases and selenoprotein K in tumour progression.

Effects of selenium status, dietary glucosinolate intake and serum glutathione S-transferase α activity on the risk of benign prostatic hyperplasia.

UNLABELLED: Study Type--Prognosis (case control) Level of Evidence 2. What's known on the subject? and What does the study add? Geographical and ethnic differences in the distribution of BPH and the results of migrant studies indicate that not only age, androgens and genetics, but also modifiable factors may play a role in the aetiology of BPH. Oxidative stress induced by chronic inflammation could be a cause and antioxidants, including selenoproteins, may reduce the risk. The published data related to this topic are scarce and are mainly based on cross-sectional and case-control studies. In a nested case-control study, we observed a significant inverse association between serum selenium concentrations and the risk of BPH. These results need to be confirmed in larger, prospective epidemiological studies. Prostate enlargement is an increasing health problem as a result of an ageing population in many countries. Modifiable factors may also play a role. In the present study, before this antioxidant can be recommended as a preventive measure. OBJECTIVE: • To determine whether geographical differences in the distribution of benign prostatic hyperplasia (BPH) and migrant studies indicate that modifiable factors play a role in the aetiology of BPH. Oxidative stress produced by chronic inflammation could represent one of the causes, and antioxidants, including selenoproteins, may reduce the risk. SUBJECTS AND METHODS: • Conditional logistic regression was used to examine the associations of serum selenium and selenoprotein P concentrations and glutathione peroxidase activity with respect to the risk of BPH in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort, including 111 cases and 214 matched controls. • In addition, dietary glucosinolate intake and the serum glutathione S-transferase α concentration was investigated. RESULTS: • The risk of BPH significantly decreased with an increasing serum selenium concentration; the risk estimate was 0.83 (35% CI 0.69-0.99) per 10 µg/L increase in serum selenium concentration. • However, no significant association was present for serum selenoprotein P concentration or glutathione peroxidase activity. Risk estimates for BPH decreased with a higher intake of glucosinolates, although the results were not statistically significant. CONCLUSION: • A low serum selenium concentration may increase the risk of BPH, although the findings reported in the present study need to be confirmed in larger, well-designed epidemiological studies.

Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg).

BACKGROUND: It has been suggested that a higher calcium intake might favourably modify cardiovascular risk factors. However, findings of an ultimately decreased risk of cardiovascular disease (CVD) are limited. Instead, recent evidence warns that taking calcium supplements might increase myocardial infarction (MI) risk. OBJECTIVE: To prospectively evaluate the associations of dietary calcium intake and calcium supplementation with MI and stroke risk and overall CVD mortality. METHODS: Data from 23 980 Heidelberg cohort participants of the European Prospective Investigation into Cancer and Nutrition study, aged 35-64 years and free of major CVD events at recruitment, were analysed. Multivariate Cox regression models were used to estimate HRs and 95% CIs. RESULTS: After an average follow-up time of 11 years, 354 MI and 260 stroke cases and 267 CVD deaths were documented. Compared with the lowest quartile, the third quartile of total dietary and dairy calcium intake had a significantly reduced MI risk, with a HR of 0.69 (95% CI 0.50 to 0.94) and 0.68 (95% CI 0.50 to 0.93), respectively. Associations for stroke risk and CVD mortality were overall null. In comparison with non-users of any supplements, users of calcium supplements had a statistically significantly increased MI risk (HR=1.86; 95% CI 1.17 to 2.96), which was more pronounced for calcium supplement only users (HR=2.39; 95% CI 1.12 to 5.12). CONCLUSIONS: Increasing calcium intake from diet might not confer significant cardiovascular benefits, while calcium supplements, which might raise MI risk, should be taken with caution.

The association between dietary lignans, phytoestrogen-rich foods, and fiber intake and postmenopausal breast cancer risk: a German case-control study.

Phytoestrogens are structurally similar to estrogens and may affect breast cancer risk by mimicking estrogenic/antiestrogenic properties. In Western societies, whole grains and possibly soy foods are rich sources of phytoestrogens. A population-based case-control study in German postmenopausal women was used to evaluate the association of phytoestrogen-rich foods and dietary lignans with breast cancer risk. Dietary data were collected from 2,884 cases and 5,509 controls using a validated food-frequency questionnaire, which included additional questions phytoestrogen-rich foods. Associations were assessed using conditional logistic regression. All analyses were adjusted for relevant risk and confounding factors. Polytomous logistic regression analysis was performed to evaluate the associations by estrogen receptor (ER) status. High and low consumption of soybeans as well as of sunflower and pumpkin seeds were associated with significantly reduced breast cancer risk compared to no consumption (OR = 0.83, 95% CI = 0.70-0.97; and OR = 0.66, 95% CI = 0.77-0.97, respectively). The observed associations were not differential by ER status. No statistically significant associations were found for dietary intake of plant lignans, fiber, or the calculated enterolignans. Our results provide evidence for a reduced postmenopausal breast cancer risk associated with increased consumption of sunflower and pumpkin seeds and soybeans.

Vitamin/mineral supplementation and cancer, cardiovascular, and all-cause mortality in a German prospective cohort (EPIC-Heidelberg).

PURPOSE: To prospectively evaluate the association of vitamin/mineral supplementation with cancer, cardiovascular, and all-cause mortality. METHODS: In the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg), which was recruited in 1994-1998, 23,943 participants without pre-existing cancer and myocardial infarction/stroke at baseline were included in the analyses. Vitamin/mineral supplementation was assessed at baseline and during follow-up. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After an average follow-up time of 11 years, 1,101 deaths were documented (cancer deaths = 513 and cardiovascular deaths = 264). After adjustment for potential confounders, neither any vitamin/mineral supplementation nor multivitamin supplementation at baseline was statistically significantly associated with cancer, cardiovascular, or all-cause mortality. However, baseline users of antioxidant vitamin supplements had a significantly reduced risk of cancer mortality (HR: 0.52; 95% CI: 0.28, 0.97) and all-cause mortality (HR: 0.58; 95% CI: 0.38, 0.88). In comparison with never users, baseline non-users who started taking vitamin/mineral supplements during follow-up had significantly increased risks of cancer mortality (HR: 1.74; 95% CI: 1.09, 2.77) and all-cause mortality (HR: 1.58; 95% CI: 1.17, 2.14). CONCLUSIONS: Based on limited numbers of users and cases, this cohort study suggests that supplementation of antioxidant vitamins might possibly reduce cancer and all-cause mortality. The significantly increased risks of cancer and all-cause mortality among baseline non-users who started taking supplements during follow-up may suggest a "sick-user effect," which researchers should be cautious of in future observational studies.

Effects of selenium status and polymorphisms in selenoprotein genes on prostate cancer risk in a prospective study of European men.

BACKGROUND: Evidence for an association between selenium status and prostate cancer risk is still inconclusive. Anticarcinogenic effects of selenium are supposedly mediated through cellular protective and redox properties of selenoenzymes in vivo. We evaluated the association between serum selenium status and prostate cancer risk in a population with relative low selenium concentrations considering effect modification by genetic variants in selenoprotein genes. MATERIALS AND METHODS: A case-control study of 248 incident prostate cancer cases and 492 matched controls was nested within the EPIC-Heidelberg cohort. Baseline blood samples were analyzed for serum selenium and selenoprotein P concentrations and glutathione peroxidase activity. Genotyping was carried out for SEP15 (rs5859, rs540049), SEPP1 (rs3877899, rs7579), GPX1 (rs1050450), and GPX4 (rs713041). Conditional logistic regression was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: The OR for prostate cancer was 0.89 (95% CI, 0.79-1.01) per 10 µg/L increase of serum selenium concentration. This association was modified by rs1050450 (C>T) in GPX1 (P(interaction) = 0.03), with carriers of one or two T alleles having a significantly reduced OR of 0.87 (95% CI, 0.76-0.99). Furthermore, there was an association between rs7579 genotype in SEPP1 and prostate cancer risk (OR, 1.72; 95% CI, 0.99-2.98). CONCLUSIONS: Our results support a role of selenium and polymorphisms in selenoenzymes in prostate cancer etiology, which warrants confirmation in future studies. IMPACT: These findings might help to explain biological effects of selenium in prostate cancer development in order to overcome inconsistencies arising from former studies.

Consistency of vitamin and/or mineral supplement use and demographic, lifestyle and health-status predictors: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort.

Cross-sectional studies suggest that dietary supplement use is associated with favourable demographic and lifestyle factors and certain health conditions. However, factors that affect the consistency of supplement use have not been investigated in prospective cohort studies. The aim of the present study was to seek baseline demographic, lifestyle and health-status predictors of subsequent consistent vitamin and/or mineral supplement use. A total of 8968 men and 10,672 women of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort, who answered the supplement-use questions in the baseline survey and two follow-up surveys, were categorised into three groups: consistent, inconsistent and never users. At baseline, 28.5 % of men and 38.6 % of women reported vitamin and/or mineral supplement use. After a median follow-up of 8.5 years, 14.6 % of men and 22.9 % of women were consistent users. During follow-up, 36.0 % of male and 26.6 % of female initial users stopped supplement use, whereas 27.8 % of male and 39.4 % of female initial non-users started supplement use. Women were more likely to be consistent users than men. Older age (≥ 50 years), lower BMI (< 25 kg/m2) and self-reported hyperlipidaemia were common predictors of consistent use for both sexes. Additional predictors included higher educational level for men, and being more physically active and higher lifetime alcohol consumption for women. Consistent users had the highest intake of dairy products, fish, fruits and vegetables, and wine but the lowest intake of total meat. We concluded that supplement use is a fairly unstable behaviour in free-living individuals. Individuals with a favourable lifestyle and healthier diet are more likely to show consistent supplementation.

Region-specific nutrient intake patterns exhibit a geographical gradient within and between European countries.

Until recently, the study of nutrient patterns was hampered at an international level by a lack of standardization of both dietary methods and nutrient databases. We aimed to describe the diversity of nutrient patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC) study at population level as a starting point for future nutrient pattern analyses and their associations with chronic diseases in multi-center studies. In this cross-sectional study, 36,034 persons aged 35-74 y were administered a single, standardized 24-h dietary recall. Intake of 25 nutrients (excluding intake from dietary supplements) was estimated using a standardized nutrient database. We used a graphic presentation of mean nutrient intakes by region and sex relative to the overall EPIC means to contrast patterns within and between 10 European countries. In Mediterranean regions, including Greece, Italy, and the southern centers of Spain, the nutrient pattern was dominated by relatively high intakes of vitamin E and monounsaturated fatty acids (MUFA), whereas intakes of retinol and vitamin D were relatively low. In contrast, in Nordic countries, including Norway, Sweden, and Denmark, reported intake of these same nutrients resulted in almost the opposite pattern. Population groups in Germany, The Netherlands, and the UK shared a fatty acid pattern of relatively high intakes of PUFA and SFA and relatively low intakes of MUFA, in combination with a relatively high intake of sugar. We confirmed large variability in nutrient intakes across the EPIC study populations and identified 3 main region-specific patterns with a geographical gradient within and between European countries.