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Background: It has long been proposed that albumin, bilirubin and uric acid may inhibit cancer development due to their anti-oxidative properties. However, there is a lack of population-based studies on blood levels of these molecules and cancer risk.Methods: Associations between pre-diagnostic serum albumin, bilirubin and uric acid and the risks of common cancers as well as cancer death in the EPIC-Heidelberg cohort were evaluated by multivariable Cox regression analyses. A case-cohort sample including a random subcohort (n=2739) and all incident cases of breast (n=627), prostate (n=554), colorectal (n=256), and lung cancer (n=195) as well as cancer death (n=761) that occurred between baseline (1994-1998) and 2009 was used.Results: Albumin levels were inversely associated with breast cancer risk (hazard ratioQuartile 4 vs Quartile 1 (95% CI): 0.71 (0.51, 0.99), Plinear trend=0.004) and overall cancer mortality (HRQ4 vs Q1 (95% CI): 0.64 (0.48, 0.86), Plinear trend<0.001) after multivariable adjustment. Uric acid levels were also inversely associated with breast cancer risk (HRQ4 vs Q1 (95% CI): 0.72 (0.53, 0.99), Plinear trend=0.043) and cancer mortality (HRQ4 vs Q1 (95% CI): 0.75 (0.58, 0.98), Plinear trend=0.09). There were no significant associations between albumin or uric acid and prostate, lung and colorectal cancer. Serum bilirubin was not associated with any cancer end point.Conclusions: The present findings indicate that higher levels of albumin and uric acid are related to lower risks of breast cancer and cancer mortality. Further studies are needed to assess whether the observed associations are causal. [ABSTRACT FROM AUTHOR]

Background: High iron load and red meat consumption could increase the risk of cardiovascular diseases (CVDs). As red meat is the main source of heme iron, which is in turn a major determinant of increased iron load, adverse cardiometabolic effects of meat consumption could be mediated by increased iron load. Objective: The object of the studywas to assess whether associations between red meat consumption and CVD risk are mediated by iron load in a population-based human study. Design: We evaluated relations between red meat consumption, iron load (plasma ferritin), and risk of CVD in the prospective EPIC-Heidelberg Study using a case-cohort sample including a random subcohort (n = 2738) and incident cases of myocardial infarction (MI, n = 555), stroke (n = 513), and CVD mortality (n = 381). Following a 4-step mediation analysis, associations between red meat consumption and iron load, red meat consumption and CVD risk, and iron load and CVD risk were assessed by multivariable regression models before finally testing to which degree associations between red meat consumption and CVD risk were attenuated by adjustment for iron status. Results: Red meat consumption was significantly positively associated with ferritin concentrations and MI risk [HR per 50 g daily intake: 1.18 (95% CI: 1.05, 1.33)], but no significant associations with stroke risk and CVD mortality were observed. While direct associations between ferritin concentrations and MI risk as well as CVD mortality were significant in age- and sex-adjusted Cox regression models, these associations were substantially attenuated and no longer significant after multivariable adjustment for classical CVD risk factors. Strikingly, ferritin concentrations were positively associated with a majority of classical CVD risk factors (age, male sex, alcohol intake, obesity, inflammation, and lower education). Conclusion: Increased ferritin concentrations may be a marker of an overall unfavorable risk factor profile rather than a mediator of greater CVD risk due to meat consumption. [ABSTRACT FROM AUTHOR]

The pro- or anti-inflammatory bioactivity of dietary essential linoleic acid (LA) and alpha-linolenic acid (ALA) is mainly attributed to rate-limiting delta-6 desaturase (D6D) activity. The aim of this study was to analyze mechanisms of D6D-substrates ALA, LA and D6D-product gamma-linolenic acid (GLA) under D6D-deficient conditions. Fatty acid profiles (GC-MS), D6D gene expression (real-time RT-PCR) and NFκB activity (luciferase assay) were assessed in HEK293 cells. FADS2 gene expression was approved being marginal. Incubation with ALA or LA did not increase D6D products but their elongase products C20:3n-3 and C20:2n-6. Bypassing the D6D, GLA elevated C20:3n-6 and C20:4n-6. LA significantly increased (+18% at 60 μM;p < .001), ALA reduced (−32% at 100 μM;p < .001) and GLA did not specifically change NFκB activity. Our data indicate that D6D might not be essential for the distinct effects of LA and ALA on NFκB activity. [ABSTRACT FROM PUBLISHER]

We identified urinary polyphenol metabolite patterns by a novel algorithm that combines dimension reduction and variable selection methods to explain polyphenol-rich food intake, and compared their respective performance with that of single biomarkers in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The study included 475 adults from four European countries (Germany, France, Italy, and Greece). Dietary intakes were assessed with 24-h dietary recalls (24-HDR) and dietary questionnaires (DQ). Thirty-four polyphenols were measured by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS-MS) in 24-h urine. Reduced rank regression-based variable importance in projection (RRR-VIP) and least absolute shrinkage and selection operator (LASSO) methods were used to select polyphenol metabolites. Reduced rank regression (RRR) was then used to identify patterns in these metabolites, maximizing the explained variability in intake of pre-selected polyphenol-rich foods. The performance of RRR models was evaluated using internal cross-validation to control for over-optimistic findings from over-fitting. High performance was observed for explaining recent intake (24-HDR) of red wine (r = 0.65; AUC = 89.1%), coffee (r = 0.51; AUC = 89.1%), and olives (r = 0.35; AUC = 82.2%). These metabolite patterns performed better or equally well compared to single polyphenol biomarkers. Neither metabolite patterns nor single biomarkers performed well in explaining habitual intake (as reported in the DQ) of polyphenol-rich foods. This proposed strategy of biomarker pattern identification has the potential of expanding the currently still limited list of available dietary intake biomarkers. [ABSTRACT FROM AUTHOR]

Background: Obesity can lead to ectopic pancreatic fat accumulation and increase the risk for type 2 diabetes. Smaller intervention trials have shown a decrease in pancreatic fat content (PFC) with weight loss, and we intended to investigate the effects of weight loss on PFC in a larger trial. Methods: Data from the HELENA-Trial, a randomized controlled trial (RCT) among 137 non-diabetic obese adults were used. The study cohort was classified into 4 quartiles based on weight change between baseline and 12 weeks post-intervention. Changes in PFC (baseline, 12 weeks and 50 weeks post-intervention) upon weight loss were analyzed by linear mixed models. Spearman's coefficients were used to obtain correlations between anthropometric parameters, blood biochemical markers, and PFC. Results: At baseline, PFC only showed a significant correlation with visceral adipose tissue (VAT) (r = 0.41). Relative changes in PFC were significantly (p = 0.01) greater in Q4 (−30.8 ± 5.7%) than in Q1 (1.3 ± 6.7%). These differences remained similar after one year. However, when adjusting the statistical analyses for changes in VAT, the differences in PFC between Q1 and Q4 were no longer statistically significant. Conclusion: Weight loss is associated with a decrease in PFC. However, the reduction of PFC is not independent from reductions in VAT. Unlike VAT, PFC was not associated with metabolic biomarkers. [ABSTRACT FROM AUTHOR]

Background: Preliminary evidence suggests that weight loss among obese has differential metabolic effects depending on the presence of non-alcoholic fatty liver disease (NAFLD). We assessed whether NAFLD predisposes to differential changes in liver fat content, liver function, and metabolic parameters upon diet-induced weight loss in a 50-week intervention trial. Methods: 143 overweight and obese non-smokers underwent a 12-week dietary intervention and a 38-week follow-up. Diet-induced changes in anthropometric measures, circulating biomarkers, and magnetic resonance (MR)-derived liver fat content and adipose tissue volumes were evaluated by mixed linear models stratifying by NAFLD at baseline. Results: The prevalence of NAFLD at baseline was 52%. Diet-induced weight loss after 12 (NAFLD: 4.8 ± 0.5%, No NAFLD: 5.1 ± 0.5%) and 50 weeks (NAFLD: 3.5 ± 0.7%, No NAFLD: 3.5 ± 0.9%) was similar in both groups, while the decrease in liver fat was significantly greater in the NAFLD group (week 12: 32.9 ± 9.5% vs. 6.3 ± 4.0%; week 50: 23.3 ± 4.4% vs. 5.0 ± 4.2%). Decreases in biomarkers of liver dysfunction (GGT, ALT, AST) and HOMA IR were also significantly greater in the NAFLD group. Other metabolic parameters showed no significant differences. Conclusion: Our data suggest that individuals with NAFLD show greater improvements of liver function and insulin sensitivity after moderate diet-induced weight loss than individuals without NAFLD. [ABSTRACT FROM AUTHOR]