Selenium and Vitamin E for Prevention of Non-Muscle-Invasive Bladder Cancer Recurrence and Progression: A Randomized Clinical Trial.

Importance: Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer. Objective: To determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC. Design, Setting, and Participants: This multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK. A total of 755 patients were screened for inclusion; 484 did not meet the inclusion criteria, and 1 declined to participate. A total of 270 patients were randomly assigned to 4 groups (selenium plus placebo, vitamin E plus placebo, selenium plus vitamin E, and placebo plus placebo) in a double-blind fashion between July 17, 2007, and October 10, 2011. Eligibility included initial diagnosis of NMIBC (stages Ta, T1, or Tis); randomization within 12 months of first transurethral resection was required. Interventions: Oral selenium (200 µg/d of high-selenium yeast) and matched vitamin E placebo, vitamin E (200 IU/d of d-alfa-tocopherol) and matched selenium placebo, selenium and vitamin E, or placebo and placebo. Main Outcome and Measures: Recurrence-free interval (RFI) on an intention-to-treat basis (analyses completed on November 28, 2022). Results: The study randomized 270 patients (mean [SD] age, 68.9 [10.4] years; median [IQR] age, 69 [63-77] years; 202 male [75%]), with 65 receiving selenium and vitamin E placebo, 71 receiving vitamin E and selenium placebo, 69 receiving selenium and vitamin E, and 65 receiving both placebos. Median overall follow-up was 5.5 years (IQR, 5.1-6.1 years); 228 patients (84%) were followed up for more than 5 years. Median treatment duration was 1.5 years (IQR, 0.9-2.5 years). The study was halted because of slow accrual. For selenium (n = 134) vs no selenium (n = 136), there was no difference in RFI (hazard ratio, 0.92; 95% CI, 0.65-1.31; P = .65). For vitamin E (n = 140) vs no vitamin E (n = 130), there was a statistically significant detriment to RFI (hazard ratio, 1.46; 95% CI, 1.02-2.09; P = .04). No significant differences were observed for progression-free interval or overall survival time with either supplement. Results were unchanged after Cox proportional hazards regression modeling to adjust for known prognostic factors. In total, 1957 adverse events were reported; 85 were serious adverse events, and all were considered unrelated to trial treatment. Conclusions and Relevance: In this randomized clinical trial of selenium and vitamin E, selenium supplementation did not reduce the risk of recurrence in patients with NMIBC, but vitamin E supplementation was associated with an increased risk of recurrence. Neither selenium nor vitamin E influenced progression or overall survival. Vitamin E supplementation may be harmful to patients with NMIBC, and elucidation of the underlying biology is required. Trial Registration: isrctn.org Identifier: ISRCTN13889738.

Dietary vitamin D intake and the bladder cancer risk: A pooled analysis of prospective cohort studies.

BACKGROUND & AIMS: Diet may play an essential role in the aetiology of bladder cancer (BC). Vitamin D is involved in various biological functions which have the potential to prevent BC development. Besides, vitamin D also influences the uptake of calcium and phosphorus, thereby possibly indirectly influencing the risk of BC. The aim of the present study was to investigate the relation between vitamin D intake and BC risk. METHODS: Individual dietary data were pooled from ten cohort studies. Food item intake was converted to daily intakes of vitamin D, calcium and phosphorus. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) were obtained using Cox-regression models. Analyses were adjusted for gender, age and smoking status (Model 1), and additionally for the food groups fruit, vegetables and meat (Model 2). Dose-response relationships (Model 1) were examined using a nonparametric test for trend. RESULTS: In total, 1994 cases and 518,002 non-cases were included in the analyses. The present study showed no significant associations between individual nutrient intake and BC risk. A significant decreased BC risk was observed for high vitamin D intake with moderate calcium and low phosphorus intake (Model 2: HRhigh vitD, mod Ca, low P: 0.77, 95% CI: 0.59-1.00). No significant dose-response analyses were observed. CONCLUSION: The present study showed a decreased BC risk for high dietary vitamin D intake in combination with low calcium intake and moderate phosphorus intake. The study highlights the importance of examining the effect of a nutrient in combination with complementary nutrients for risk assessment. Future research should focus on nutrients in a wider context and in nutritional patterns.

Krill oil supplementation's effect on school grades in typically developing adolescents.

Long-chain polyunsaturated fatty acids (LCPUFA) are important for brain development and functioning and with that, possibly school performance. Several cross-sectional studies have shown significant positive associations between fish consumption, an important source of LCPUFA and school grades in adolescents. The effect of LCPUFA supplementation on school grades in adolescents has not been investigated yet. The goal of the current study was to investigate (I) the associations between the Omega-3 Index (O3I) at baseline and after 12 months respectively and school grades and (II) the effect of one year krill oil supplementation (source of LCPUFA) on school grades in adolescents with a low O3I at baseline. A double-blind randomised placebo-controlled trial with repeated measurements was executed. Participants received either 400 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day for the first three months in Cohort 1 and the nine months thereafter 800 mg EPA + DHA per day, Cohort 2 started immediately with 800 mg EPA + DHA per day,or a placebo. The O3I was monitored with a finger prick at baseline, three, six and twelve months. Subject grades for English, Dutch and math were collected, a standardised mathematics test was executed at baseline and at 12 months. Data was analysed with (I) explorative linear regressions to investigate associations at baseline and follow-up and (II) mixed model analyses separately for each of the subject grades and the standardised mathematics test to investigate the effect of supplementation after 12 months. The krill oil group had a small significant increase in the mean O3I at all time points. However, very few participants achieved the intended target O3I range of 8-11%. At baseline a significant association between baseline O3I and English grade was show, additionally a trend for an association with Dutch grade was shown. After 12 months no significant associations were found. Additionally, there was no significant effect of krill oil supplementation on subject grades or standardised mathematics test score. In this study, no significant effect of krill oil supplementation on subject grades or standardised mathematics test performance was found. However, as many participants dropped out and/or were non-adherent, results should be interpreted with caution.

Tea consumption and risk of bladder cancer in the Bladder Cancer Epidemiology and Nutritional Determinants (BLEND) Study: Pooled analysis of 12 international cohort studies.

BACKGROUND & AIMS: Tea has been shown to be associated with reduced risk of several diseases including cardiovascular diseases, stroke, metabolic syndrome, and obesity. However, the results on the relationship between tea consumption and bladder cancer are conflicting. This research aimed to assess the association between tea consumption and risk of bladder cancer using a pooled analysis of prospective cohort data. METHODS: Individual data from 532,949 participants in 12 cohort studies, were pooled for analyses. Cox regression models stratified by study centre was used to estimate hazard ratios (HR) and corresponding 95% CIs. Fractional polynomial regression models were used to examine the dose-response relationship. RESULTS: A higher level of tea consumption was associated with lower risk of bladder cancer incidence (compared with no tea consumption: HR = 0.87, 95% C.I. = 0.77-0.98 for low consumption; HR = 0.86, 95% C.I. = 0.77-0.96 for moderate consumption; HR = 0.84, 95% C.I. = 0.75-0.95 for high consumption). When stratified by sex and smoking status, this reduced risk was statistically significant among men and current and former smokers. In addition, dose-response analyses showed a lower bladder cancer risk with increment of 100 ml of tea consumption per day (HR-increment = 0.97; 95% CI = 0.96-0.98). A similar inverse association was found among males, current and former smokers while never smokers and females showed non-significant results, suggesting potential sex-dependent effect. CONCLUSIONS: Higher consumption of tea is associated with reduced risk of bladder cancer with potential interaction with sex and smoking status. Further studies are needed to clarify the mechanisms for a protective effect of tea (e.g. inhibition of the survival and proliferation of cancer cells and anti-inflammatory mechanisms) and its interaction with smoking and sex.

Dietary fats and their sources in association with the risk of bladder cancer: A pooled analysis of 11 prospective cohort studies.

The effects of fat intake from different dietary sources on bladder cancer (BC) risk remains unidentified. Therefore, the present study aimed to investigate the association between fat intakes and BC risk by merging world data on this topic. Data from 11 cohort studies in the BLadder cancer Epidemiology and Nutritional Determinants (BLEND) study, provided sufficient information on fat intake for a total of 2731 BC cases and 544 452 noncases, which yielded 5 400 168 person-years of follow-up. Hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were estimated using Cox-regression models stratified on cohort. Analyses were adjusted for total energy intake in kilocalories, gender, smoking status (model-1) and additionally for sugar and sugar products, beers, wine, dressing and plant-based and fruits intakes (model-2). Among women, an inverse association was observed between mono-unsaturated fatty acids (MUFAs) and BC risk (HR comparing the highest with the lowest tertile: 0.73, 95% CI: 0.58-0.93, P-trend = .01). Overall, this preventative effect of MUFAs on BC risk was only observed for the nonmuscle invasive bladder cancer (NMIBC) subtype (HR: 0.69, 95% CI: 0.53-0.91, P-trend = .004). Among men, a higher intake of total cholesterol was associated with an increased BC risk (HR: 1.37, 95% CI: 1.16-1.61, P-trend = .01). No other significant associations were observed. This large prospective study adds new insights into the role of fat and oils in BC carcinogenesis, showing an inverse association between consumption of MUFAs and the development of BC among women and a direct association between higher intakes of dietary cholesterol and BC risk among men.

Specific amino acid supplementation rescues the heart from lipid overload-induced insulin resistance and contractile dysfunction by targeting the endosomal mTOR-v-ATPase axis.

OBJECTIVE: The diabetic heart is characterized by extensive lipid accumulation which often leads to cardiac contractile dysfunction. The underlying mechanism involves a pivotal role for vacuolar-type H+-ATPase (v-ATPase, functioning as endosomal/lysosomal proton pump). Specifically, lipid oversupply to the heart causes disassembly of v-ATPase and endosomal deacidification. Endosomes are storage compartments for lipid transporter CD36. However, upon endosomal deacidification, CD36 is expelled to translocate to the sarcolemma, thereby inducing myocardial lipid accumulation, insulin resistance, and contractile dysfunction. Hence, the v-ATPase assembly may be a suitable target for ameliorating diabetic cardiomyopathy. Another function of v-ATPase involves the binding of anabolic master-regulator mTORC1 to endosomes, a prerequisite for the activation of mTORC1 by amino acids (AAs). We examined whether the relationship between v-ATPase and mTORC1 also operates reciprocally; specifically, whether AA induces v-ATPase reassembly in a mTORC1-dependent manner to prevent excess lipids from entering and damaging the heart. METHODS: Lipid overexposed rodent/human cardiomyocytes and high-fat diet-fed rats were treated with a specific cocktail of AAs (lysine/leucine/arginine). Then, v-ATPase assembly status/activity, cell surface CD36 content, myocellular lipid uptake/accumulation, insulin sensitivity, and contractile function were measured. To elucidate underlying mechanisms, specific gene knockdown was employed, followed by subcellular fractionation, and coimmunoprecipitation. RESULTS: In lipid-overexposed cardiomyocytes, lysine/leucine/arginine reinternalized CD36 to the endosomes, prevented/reversed lipid accumulation, preserved/restored insulin sensitivity, and contractile function. These beneficial AA actions required the mTORC1-v-ATPase axis, adaptor protein Ragulator, and endosomal/lysosomal AA transporter SLC38A9, indicating an endosome-centric inside-out AA sensing mechanism. In high-fat diet-fed rats, lysine/leucine/arginine had similar beneficial actions at the myocellular level as in vitro in lipid-overexposed cardiomyocytes and partially reversed cardiac hypertrophy. CONCLUSION: Specific AAs acting through v-ATPase reassembly reduce cardiac lipid uptake raising the possibility for treatment in situations of lipid overload and associated insulin resistance.

Coffee consumption and risk of bladder cancer: a pooled analysis of 501,604 participants from 12 cohort studies in the BLadder Cancer Epidemiology and Nutritional Determinants (BLEND) international study.

Recent epidemiological studies have shown varying associations between coffee consumption and bladder cancer (BC). This research aims to elucidate the association between coffee consumption and BC risk by bringing together worldwide cohort studies on this topic. Coffee consumption in relation to BC risk was examined by pooling individual data from 12 cohort studies, comprising of 2601 cases out of 501,604 participants. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were obtained using multilevel Weibull regression models. Furthermore, dose-response relationships were examined using generalized least squares regression models. The association between coffee consumption and BC risk showed interaction with sex (P-interaction < 0.001) and smoking (P-interaction = 0.001). Therefore, analyses were stratified by sex and smoking. After adjustment for potential confounders, an increased BC risk was shown for high (> 500 ml/day, equivalent to > 4 cups/day) coffee consumption compared to never consumers among male smokers (current smokers: HR = 1.75, 95% CI 1.27-2.42, P-trend = 0.002; former smokers: HR = 1.44, 95% CI 1.12-1.85, P-trend = 0.001). In addition, dose-response analyses, in male smokers also showed an increased BC risk for coffee consumption of more than 500 ml/day (4 cups/day), with the risk of one cup (125 ml) increment as 1.07 (95% CI 1.06-1.08). This research suggests that positive associations between coffee consumption and BC among male smokers but not never smokers and females. The inconsistent results between sexes and the absence of an association in never smokers indicate that the associations found among male smokers is unlikely to be causal and is possibly caused by residual confounding of smoking.

Effect of 1 Year Krill Oil Supplementation on Cognitive Achievement of Dutch Adolescents: A Double-Blind Randomized Controlled Trial.

Long-chain polyunsaturated fatty acids (LCPUFA) are important for brain development and function, maybe especially during adolescence. Observational studies have demonstrated an association between fish consumption (a source of LCPUFA) and cognition in adolescents, but intervention trials are lacking. The goal of the current study was to investigate the effect of one year of krill oil (a source of LCPUFA) supplementation on the cognitive performance of adolescents with a low Omega-3 Index (O3I ≤ 5%). A double-blind, randomized, and placebo-controlled supplementation trial with repeated measurements (baseline (T0), three months (T1), six months (T2), and 12 months (T3)) in adolescents (267 randomized) was executed. Participants were randomized to 400 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day in Cohort I or placebo and 800 mg EPA + DHA per day in Cohort II or placebo. O3I was monitored by a finger prick at all time points. At T0, T2, and T3, participants executed a neurocognitive test battery. Covariate corrected mixed models were run with either condition (krill or placebo) or O3I as predictors. Krill oil supplementation led to a small but significant increase in mean O3I, but few participants increased to the intended O3I range (8-11%). There was no significant effect of supplementation on the neurocognitive tests, nor a relationship between O3I and neurocognitive test scores. The increase in O3I was small in most participants, probably due to non-compliance. Possibly the increase in O3I was too small to demonstrate an effect. More research on the influence of LCPUFAs on cognition in adolescents is needed.

The association between coffee consumption and bladder cancer in the bladder cancer epidemiology and nutritional determinants (BLEND) international pooled study.

BACKGROUND: Inconsistent results for coffee consumption and bladder cancer (BC) risk have been shown in epidemiological studies. This research aims to increase the understanding of the association between coffee consumption and BC risk by bringing together worldwide case-control studies on this topic. METHODS: Data were collected from 13 case-control comprising of 5,911 cases and 16,172 controls. Pooled multivariate odds ratios (ORs), with corresponding 95% confidence intervals (CIs), were obtained using multilevel logistic regression models. Furthermore, linear dose-response relationships were examined using fractional polynomial models. RESULTS: No association of BC risk was observed with coffee consumption among smokers. However, after adjustment for age, gender, and smoking, the risk was significantly increased for never smokers (ever vs. never coffee consumers: ORmodel2 1.30, 95% CI 1.06-1.59; heavy (> 4 cups/day) coffee consumers vs. never coffee consumers: ORmodel2 1.52, 95% CI 1.18-1.97, p trend = 0.23). In addition, dose-response analyses, in both the overall population and among never smokers, also showed a significant increased BC risk for coffee consumption of more than four cups per day. Among smokers, a significant increased BC risk was shown only after consumption of more than six cups per day. CONCLUSION: This research suggests that positive associations between coffee consumption and BC among never smokers but not smokers.

Stages of behavioural change after direct-to-consumer disease risk profiling: study protocol of two integrated controlled pragmatic trials.

BACKGROUND: The incidence and prevalence of chronic diseases have reached epidemic proportions during the last decades and are not expected to diminish. Chronic diseases increasingly affect younger individuals too, with over 40% of all deaths due to non-communicable diseases occurring before the age of 70. This has led to the development of information services aimed at preventive health care, such as Health Potential®. This counselling service estimates a personal disease risk of a carefully selected list of preventable common chronic diseases that have both a genetic and a lifestyle component of development. The results are delivered face-to-face by a lifestyle counsellor, simultaneously stimulating initial steps towards behaviour change. This information can assist in lifestyle decision-making. METHODS/DESIGN: The primary aim is to study the effect of the Health Potential® service on change in lifestyle behaviour in distinguishable customer populations. The secondary aims are (1) to study the effect of the Health Potential® service on determinants of behaviour change, (2) to study the effect of additional lifestyle counselling on behaviour change and determinants thereof, and (3) to describe the characteristics of the Health Potential® customer. The study consists of two integrated designs: (A) a two-armed non-randomised controlled pre-test/post-test trial (1.5:1 ratio), followed by (B) a two-armed randomised controlled pre-test/post-test trial (1:1 ratio), resulting in three study arms. Participants are clients of local prevention clinics, purchasing a personalised health check (PHC; intervention condition), consisting of Health Potential® and a general health check, or the general health check alone (GHC; control condition) (part A). PHC participants will be randomised to receive four additional lifestyle counselling sessions over a period of 3 months (part B). DISCUSSION: This research can provide valuable insights into the effectiveness of and possible ways forward in the field of personalised prevention making use of lifestyle interventions enriched with modern genetic advancements. TRIAL REGISTRATION: Nederlands Trial Register, NTR6289 and NTR6288 . Registered on 24 February 2017.

PUFA status at birth and allergy-related phenotypes in childhood: a pooled analysis of the Maastricht Essential Fatty Acid Birth (MEFAB) and RHEA birth cohorts.

Lower prenatal exposure to n-3 PUFA relative to n-6 PUFA has been hypothesised to influence allergy development, but evidence remains largely inconsistent. In the Dutch Maastricht Essential Fatty Acid Birth (MEFAB) (n 293) and Greek RHEA Mother-Child (n 213) cohorts, we investigated whether cord blood phospholipid PUFA concentrations are associated with symptoms of wheeze, asthma, rhinitis and eczema at the age of 6-7 years. Information on allergy-related phenotypes was collected using validated questionnaires. We estimated relative risks (RR) and 95 % CI for associations of PUFA with child outcomes using multivariable generalised linear regression models. In pooled analyses, higher concentration of the n-3 long-chain EPA and DHA and a higher total n-3:n-6 PUFA ratio were associated with lower risk of current wheeze (RR 0·61; 95 % CI 0·45, 0·82 per sd increase in EPA+DHA and 0·54; 95 % CI 0·39, 0·75 per unit increase in the n-3:n-6 ratio) and reduced asthma risk (RR 0·50; 95 % CI 0·31, 0·79 for EPA+DHA and 0·43; 95 % CI 0·26, 0·70 for the n-3:n-6 ratio). No associations were observed for other allergy-related phenotypes. The results were similar across cohorts. In conclusion, higher EPA and DHA concentrations and a higher n-3:n-6 fatty acid ratio at birth were associated with lower risk of child wheeze and asthma. Our findings suggest that dietary interventions resulting in a marked increase in the n-3:n-6 PUFA ratio, and mainly in n-3 long-chain PUFA intake in late gestation, may reduce the risk of asthma symptoms in mid-childhood.

Fish and seafood consumption during pregnancy and the risk of asthma and allergic rhinitis in childhood: a pooled analysis of 18 European and US birth cohorts.

Background: It has been suggested that prenatal exposure to n-3 long-chain fatty acids protects against asthma and other allergy-related diseases later in childhood. The extent to which fish intake in pregnancy protects against child asthma and rhinitis symptoms remains unclear. We aimed to assess whether fish and seafood consumption in pregnancy is associated with childhood wheeze, asthma and allergic rhinitis. Methods: We pooled individual data from 60 774 mother-child pairs participating in 18 European and US birth cohort studies. Information on wheeze, asthma and allergic rhinitis prevalence was collected using validated questionnaires. The time periods of interest were: infancy (0-2 years), preschool age (3-4 years), and school age (5-8 years). We used multivariable generalized models to assess associations of fish and seafood (other than fish) consumption during pregnancy with child respiratory outcomes in cohort-specific analyses, with subsequent random-effects meta-analyses. Results: The median fish consumption during pregnancy ranged from 0.44 times/week in The Netherlands to 4.46 times/week in Spain. Maternal fish intake during pregnancy was not associated with offspring wheeze symptoms in any age group nor with the risk of child asthma [adjusted meta-analysis relative risk (RR) per 1-time/week = 1.01, 95% confidence interval 0.97-1.05)] and allergic rhinitis at school age (RR = 1.01, 0.99-1.03). These results were consistently found in further analyses by type of fish and seafood consumption and in sensitivity analyses. Conclusion: We found no evidence supporting a protective association of fish and seafood consumption during pregnancy with offspring symptoms of wheeze, asthma and allergic rhinitis from infancy to mid childhood.

Phase III randomised chemoprevention study with selenium on the recurrence of non-invasive urothelial carcinoma. The SELEnium and BLAdder cancer Trial.

BACKGROUND: In Belgium, bladder cancer (BC) is the fifth most common cancer in men. The per-patient lifetime cost is high. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of BC. We therefore hypothesised that selenium may be suitable for chemoprevention of recurrence of BC. METHOD: The Selenium and Bladder Cancer Trial (SELEBLAT) was an academic phase III placebo-controlled, double-blind, randomised clinical trial designed to determine the effect of selenium on recurrence of non-invasive urothelial carcinoma conducted in 14 Belgian hospitals. Patients were randomly assigned by a computer program to oral selenium yeast 200 µg once a day or placebo for three years, in addition to standard care. All study personnel and participants were blinded to treatment assignment for the duration of the study. All randomised patients were included in the intention to treat (ITT) and safety analyses. Per protocol analyses (PPAs) included all patients in the study three months after start date. RESULTS: Between September 18, 2009 and April 18, 2013, 151 and 141 patients were randomised in the selenium and placebo group. Patients were followed until December 31, 2015. The ITT analysis resulted in 43 (28%; 95% CI, 0.21-0.35) and 45 (32%; 95% CI, 0.24-0.40) recurrences in the selenium and placebo group. The hazard ratio (HR) was 0.85 (95% CI, 0.56-1.29; p = 0.44) while the HR for the PPA resulted in 42 and 39 (28%; 95% CI, 0.20-0.35) recurrences in the selenium and placebo group (HR = 0.96 [95% CI, 0.62-1.48]; p = 0.93). CONCLUSION: Selenium supplementation does not lower the probability of recurrence in BC patients.

Modifiable risk factors for the prevention of bladder cancer: a systematic review of meta-analyses.

Each year, 430,000 people are diagnosed with bladder cancer. Due to the high recurrence rate of the disease, primary prevention is paramount. Therefore, we reviewed all meta-analyses on modifiable risk factors of primary bladder cancer. PubMed, Embase and Cochrane database were systematically searched for meta-analyses on modifiable risk factors published between 1995 and 2015. When appropriate, meta-analyses (MA) were combined in meta-meta-analysis (MMA). If not, the most comprehensive MA was selected based on the number of primary studies included. Probability of causation was calculated for individual factors and a subset of lifestyle factors combined. Of 1496 articles identified, 5 were combined in MMA and 21 were most comprehensive on a single risk factor. Statistically significant associations were found for current (RR 3.14) or former (RR 1.83) cigarette smoking, pipe (RR 1.9) or cigar (RR 2.3) smoking, antioxidant supplementation (RR 1.52), obesity (RR 1.10), higher physical activity levels (RR 0.86), higher body levels of selenium (RR 0.61) and vitamin D (RR 0.75), and higher intakes of: processed meat (RR 1.22), vitamin A (RR 0.82), vitamin E (RR 0.82), folate (RR 0.84), fruit (RR 0.77), vegetables (RR 0.83), citrus fruit (RR 0.85), and cruciferous vegetables (RR 0.84). Finally, three occupations with the highest risk were tobacco workers (RR 1.72), dye workers (RR 1.58), and chimney sweeps (RR 1.53). The probability of causation for individual factors ranged from 4 to 68 %. The combined probability of causation was 81.8 %. Modification of lifestyle and occupational exposures can considerably reduce the bladder cancer burden. While smoking remains one of the key risk factors, also several diet-related and occupational factors are very relevant.

Association between Blood Omega-3 Index and Cognition in Typically Developing Dutch Adolescents.

The impact of omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) on cognition is heavily debated. In the current study, the possible association between omega-3 LCPUFAs in blood and cognitive performance of 266 typically developing adolescents aged 13-15 years is investigated. Baseline data from Food2Learn, a double-blind and randomized placebo controlled krill oil supplementation trial in typically developing adolescents, were used for the current study. The Omega-3 Index was determined with blood from a finger prick. At baseline, participants finished a neuropsychological test battery consisting of the Letter Digit Substitution Test (LDST), D2 test of attention, Digit Span Forward and Backward, Concept Shifting Test and Stroop test. Data were analyzed with multiple regression analyses with correction for covariates. The average Omega-3 Index was 3.83% (SD 0.60). Regression analyses between the Omega-3 Index and the outcome parameters revealed significant associations with scores on two of the nine parameters. The association between the Omega-3 Index and both scores on the LDST (ß = 0.136 and p = 0.039), and the number of errors of omission on the D2 (ß = -0.053 and p = 0.007). This is a possible indication for a higher information processing speed and less impulsivity in those with a higher Omega-3 Index.

Selenium for preventing cancer.

BACKGROUND: This review is an update of the first Cochrane publication on selenium for preventing cancer (Dennert 2011).Selenium is a metalloid with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVES: Two research questions were addressed in this review: What is the evidence for:1. an aetiological relation between selenium exposure and cancer risk in humans? and2. the efficacy of selenium supplementation for cancer prevention in humans? SEARCH METHODS: We conducted electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 1), MEDLINE (Ovid, 1966 to February 2013 week 1), EMBASE (1980 to 2013 week 6), CancerLit (February 2004) and CCMed (February 2011). As MEDLINE now includes the journals indexed in CancerLit, no further searches were conducted in this database after 2004. SELECTION CRITERIA: We included prospective observational studies (cohort studies including sub-cohort controlled studies and nested case-control studies) and randomised controlled trials (RCTs) with healthy adult participants (18 years of age and older). DATA COLLECTION AND ANALYSIS: For observational studies, we conducted random effects meta-analyses when five or more studies were retrieved for a specific outcome. For RCTs, we performed random effects meta-analyses when two or more studies were available. The risk of bias in observational studies was assessed using forms adapted from the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies; the criteria specified in the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias in RCTs. MAIN RESULTS: We included 55 prospective observational studies (including more than 1,100,000 participants) and eight RCTs (with a total of 44,743 participants). For the observational studies, we found lower cancer incidence (summary odds ratio (OR) 0.69, 95% confidence interval (CI) 0.53 to 0.91, N = 8) and cancer mortality (OR 0.60, 95% CI 0.39 to 0.93, N = 6) associated with higher selenium exposure. Gender-specific subgroup analysis provided no clear evidence of different effects in men and women (P value 0.47), although cancer incidence was lower in men (OR 0.66, 95% CI 0.42 to 1.05, N = 6) than in women (OR 0.90, 95% CI 0.45 to 1.77, N = 2). The most pronounced decreases in risk of site-specific cancers were seen for stomach, bladder and prostate cancers. However, these findings have limitations due to study design, quality and heterogeneity that complicate interpretation of the summary statistics. Some studies suggested that genetic factors may modify the relation between selenium and cancer risk-a hypothesis that deserves further investigation.In RCTs, we found no clear evidence that selenium supplementation reduced the risk of any cancer (risk ratio (RR) 0.90, 95% CI 0.70 to 1.17, two studies, N = 4765) or cancer-related mortality (RR 0.81, 95% CI 0.49 to 1.32, two studies, N = 18,698), and this finding was confirmed when the analysis was restricted to studies with low risk of bias. The effect on prostate cancer was imprecise (RR 0.90, 95% CI 0.71 to 1.14, four studies, N = 19,110), and when the analysis was limited to trials with low risk of bias, the interventions showed no effect (RR 1.02, 95% CI 0.90 to 1.14, three studies, N = 18,183). The risk of non-melanoma skin cancer was increased (RR 1.44, 95% CI 0.95 to 1.17, three studies, N = 1900). Results of two trials-the Nutritional Prevention of Cancer Trial (NPCT) and the Selenium and Vitamin E Cancer Trial (SELECT)-also raised concerns about possible increased risk of type 2 diabetes, alopecia and dermatitis due to selenium supplements. An early hypothesis generated by NPCT that individuals with the lowest blood selenium levels at baseline could reduce their risk of cancer, particularly of prostate cancer, by increasing selenium intake has not been confirmed by subsequent trials. As the RCT participants were overwhelmingly male (94%), gender differences could not be systematically assessed. AUTHORS' CONCLUSIONS: Although an inverse association between selenium exposure and the risk of some types of cancer was found in some observational studies, this cannot be taken as evidence of a causal relation, and these results should be interpreted with caution. These studies have many limitations, including issues with assessment of exposure to selenium and to its various chemical forms, heterogeneity, confounding and other biases. Conflicting results including inverse, null and direct associations have been reported for some cancer types.RCTs assessing the effects of selenium supplementation on cancer risk have yielded inconsistent results, although the most recent studies, characterised by a low risk of bias, found no beneficial effect on cancer risk, more specifically on risk of prostate cancer, as well as little evidence of any influence of baseline selenium status. Rather, some trials suggest harmful effects of selenium exposure. To date, no convincing evidence suggests that selenium supplements can prevent cancer in humans.

Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium.

BACKGROUND: In Belgium, bladder cancer is the fifth most common cancer in males (5.2%) and the sixth most frequent cause of death from cancer in males (3.8%). Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence. METHOD: The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at http://www.seleblat.org. Patients are randomly assigned to selenium yeast (200 µg/day) supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study. DESIGN: The SELEnium and BLAdder cancer Trial (SELEBLAT) is a phase III randomized, placebo-controlled, academic, double-blind superior trial. DISCUSSION: This is the first report on a selenium randomized trial in bladder cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00729287.

Selenium for preventing cancer

BACKGROUND: Selenium is a trace element essential to humans. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVE: Two research questions were addressed in this review: What is the evidence for: 1. an aetiological relationship between selenium exposure and cancer risk in women and men?; 2. the efficacy of selenium supplementation for cancer prevention in women and men? SEARCH STRATEGY: We searched electronic databases and bibliographies of reviews and included publications. SELECTION CRITERIA: We included prospective observational studies to answer research question (a) and randomised controlled trials (RCTs) to answer research question (b). DATA COLLECTION AND ANALYSIS: We conducted random effects meta-analyses of epidemiological data when five or more studies were retrieved for a specific outcome. We made a narrative summary of data from RCTs. MAIN RESULTS: We included 49 prospective observational studies and six RCTs. In epidemiologic data, we found a reduced cancer incidence (summary odds ratio, OR, 0.69; 95 percent confidence interval, CI, 0.53 to 0.91) and mortality (OR 0.55, 95 percent CI 0.36 to 0.83) with higher selenium exposure. Cancer risk was more pronouncedly reduced in men (incidence: OR 0.66, 95 percent CI 0.42 to 1.05) than in women (incidence: OR 0.90, 95 percent CI 0.45 to 1.77). These findings have potential limitations due to study design, quality and heterogeneity of the data, which complicated the interpretation of the summary statistics. The RCTs found no protective efficacy of selenium yeast supplementation against non-melanoma skin cancer or L-selenomethionine supplementation against prostate cancer. Study results for the prevention of liver cancer with selenium supplements were inconsistent and studies had an unclear risk of bias. The results of the Nutritional Prevention of Cancer Trial (NPCT) and SELECT raised concerns about possible harmful effects of selenium supplements. AUTHORS' CONCLUSIONS: No reliable conclusions can be drawn regarding a causal relationship between low selenium exposure and an increased risk of cancer. Despite evidence for an inverse association between selenium exposure and the risk of some types of cancer, these results should be interpreted with care due to the potential limiting factors of heterogeneity and influences of unknown biases, confounding and effect modification. The effect of selenium supplementation from RCTs yielded inconsistent results. To date, there is no convincing evidence that selenium supplements can prevent cancer in men, women or children.

Selenium for preventing cancer.

BACKGROUND: Selenium is a trace element essential to humans. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVES: Two research questions were addressed in this review: What is the evidence for1. an aetiological relationship between selenium exposure and cancer risk in women and men?2. the efficacy of selenium supplementation for cancer prevention in women and men? SEARCH STRATEGY: We searched electronic databases and bibliographies of reviews and included publications. SELECTION CRITERIA: We included prospective observational studies to answer research question (a) and randomised controlled trials (RCTs) to answer research question (b). DATA COLLECTION AND ANALYSIS: We conducted random effects meta-analyses of epidemiological data when five or more studies were retrieved for a specific outcome. We made a narrative summary of data from RCTs. MAIN RESULTS: We included 49 prospective observational studies and six RCTs. In epidemiologic data, we found a reduced cancer incidence (summary odds ratio (OR) 0.69 (95% confidence interval (CI) 0.53 to 0.91) and mortality (OR 0.55, 95% CI 0.36 to 0.83) with higher selenium exposure. Cancer risk was more pronouncedly reduced in men (incidence: OR 0.66, 95% CI 0.42 to 1.05) than in women (incidence: OR 0.90, 95% CI 0.45 to 1.77). These findings have potential limitations due to study design, quality and heterogeneity of the data, which complicated the interpretation of the summary statistics.The RCTs found no protective efficacy of selenium yeast supplementation against non-melanoma skin cancer or L-selenomethionine supplementation against prostate cancer. Study results for the prevention of liver cancer with selenium supplements were inconsistent and studies had an unclear risk of bias. The results of the Nutritional Prevention of Cancer Trial (NPCT) and SELECT raised concerns about possible harmful effects of selenium supplements. AUTHORS' CONCLUSIONS: No reliable conclusions can be drawn regarding a causal relationship between low selenium exposure and an increased risk of cancer. Despite evidence for an inverse association between selenium exposure and the risk of some types of cancer, these results should be interpreted with care due to the potential limiting factors of heterogeneity and influences of unknown biases, confounding and effect modification.The effect of selenium supplementation from RCTs yielded inconsistent results. To date, there is no convincing evidence that selenium supplements can prevent cancer in men, women or children.