Hepatic steatosis, metabolic dysfunction and risk of mortality: findings from a multinational prospective cohort study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are implicated in the aetiology of non-communicable diseases. Our study aimed to evaluate associations between NAFLD and MetS with overall and cause-specific mortality. METHODS: We used dietary, lifestyle, anthropometric and metabolic biomarker data from a random subsample of 15,784 EPIC cohort participants. NAFLD was assessed using the fatty liver index (FLI) and MetS using the revised definition. Indices for metabolic dysfunction-associated fatty liver disease (MAFLD) were calculated. The individual associations of these indices with overall and cause-specific mortality were assessed using multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs). As a subobjective, risk associations with adaptations of new classifications of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic and alcohol-related liver disease (MetALD) were also assessed. RESULTS: Among the 15,784 sub-cohort participants, a total of 1997 deaths occurred (835 due to cancer, 520 to CVD, 642 to other causes) over a median 15.6 (IQR, 12.3-17.1) years of follow-up. Compared to an FLI < 30, FLI ≥ 60 was associated with increased risks of overall mortality (HR = 1.44, 95%CI = 1.27-1.63), and deaths from cancer (HR = 1.32, 95%CI = 1.09-1.60), CVD (HR = 2.06, 95% CI = 1.61-2.63) or other causes (HR = 1.21, 95%CI = 0.97-1.51). Mortality risk associations were also elevated for individuals with MAFLD compared to those without. Individuals with MetS were at increased risk of all mortality endpoints, except cancer-specific mortality. MASLD and MetALD were associated with higher risk of overall mortality. CONCLUSIONS: Our findings based on a prospective cohort suggest that individuals with hepatic steatosis or metabolic dysfunction have a higher overall and cause-specific mortality risk.

The role of the gut microbiome in the development of hepatobiliary cancers.

Hepatobiliary cancers, including hepatocellular carcinoma and cancers of the biliary tract, share high mortality and rising incidence rates. They may also share several risk factors related to unhealthy western-type dietary and lifestyle patterns as well as increasing body weights and rates of obesity. Recent data also suggest a role for the gut microbiome in the development of hepatobiliary cancer and other liver pathologies. The gut microbiome and the liver interact bidirectionally through the "gut-liver axis," which describes the interactive relationship between the gut, its microbiota, and the liver. Here, we review the gut-liver interactions within the context of hepatobiliary carcinogenesis by outlining the experimental and observational evidence for the roles of gut microbiome dysbiosis, reduced gut barrier function, and exposure to inflammatory compounds as well as metabolic dysfunction as contributors to hepatobiliary cancer development. We also outline the latest findings regarding the impact of dietary and lifestyle factors on liver pathologies as mediated by the gut microbiome. Finally, we highlight some emerging gut microbiome editing techniques currently being investigated in the context of hepatobiliary diseases. Although much work remains to be done in determining the relationships between the gut microbiome and hepatobiliary cancers, emerging mechanistic insights are informing treatments, such as potential microbiota manipulation strategies and guiding public health advice on dietary/lifestyle patterns for the prevention of these lethal tumors.

Dietary intake of dicarbonyl compounds and changes in body weight over time in a large cohort of European adults.

Dicarbonyl compounds are highly reactive precursors of advanced glycation end products (AGE), produced endogenously, present in certain foods and formed during food processing. AGE contribute to the development of adverse metabolic outcomes, but health effects of dietary dicarbonyls are largely unexplored. We investigated associations between three dietary dicarbonyl compounds, methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG), and body weight changes in European adults. Dicarbonyl intakes were estimated using food composition database from 263 095 European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home in Relation to Anthropometry participants with two body weight assessments (median follow-up time = 5·4 years). Associations between dicarbonyls and 5-year body-weight changes were estimated using mixed linear regression models. Stratified analyses by sex, age and baseline BMI were performed. Risk of becoming overweight/obese was assessed using multivariable-adjusted logistic regression. MGO intake was associated with 5-year body-weight gain of 0·089 kg (per 1-sd increase, 95 % CI 0·072, 0·107). 3-DG was inversely associated with body-weight change (-0·076 kg, -0·094, -0·058). No significant association was observed for GO (0·018 kg, -0·002, 0·037). In stratified analyses, GO was associated with body-weight gain among women and older participants (above median of 52·4 years). MGO was associated with higher body-weight gain among older participants. 3-DG was inversely associated with body-weight gain among younger and normal-weight participants. MGO was associated with a higher risk of becoming overweight/obese, while inverse associations were observed for 3-DG. No associations were observed for GO with overweight/obesity. Dietary dicarbonyls are inconsistently associated with body weight change among European adults. Further research is needed to clarify the role of these food components in overweight and obesity, their underlying mechanisms and potential public health implications.

Associations between cooking methods and socio-demographic, dietary and anthropometric factors: results from the Swiss National Nutrition Survey.

INTRODUCTION: Appropriate cooking methods can improve food safety, decrease contaminants and increase nutrient bioavailability. Few studies assessed the sociodemographic characterization of their use in European populations. We aimed to characterize the socio-demographic, lifestyle, and anthropometric predictors of cooking methods in the Swiss population. METHODS: adults aged 18-75 years (n=2,050) participating in the cross-sectional national nutrition survey in Switzerland (menuCH) (2014-2015), representing the 7 main regions in the country. We used logistic regressions to assess the probability of presence or absence of boiled, roasted, microwaved, oven-cooked, gratinated, fried, steamed, and grilled foods by sociodemographic variables. RESULTS: Among all participants, the most frequently used cooking methods were boiling (46%), stove-cooking (19%), and steaming (8%). Single participants had a higher probability of consuming grilled or fried foods (68%) than their married counterparts and participants with obesity had a higher probability of consuming grilled or fried foods (67% or 135%) compared to those with normal weight. Divorced or separated participants had a 55% lower probability of consuming roasted foods than married participants. Those following a diet had a 57% lower probability of consuming grilled foods compared to those not on a diet. CONCLUSION: We found differences in the distribution cooking methods of the Swiss population by sociodemographic variables. Further studies should examine the link between cooking methods and disease risk.

A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk.

BACKGROUND: Alcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk. OBJECTIVE: Leveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk. METHODS: Within the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases. RESULTS: Mean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite. CONCLUSIONS: Increasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.

Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study.

Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the non-enzymatic reaction between amino acids and reducing sugars, or dicarbonyls as intermediate compounds. Experimental studies suggest that AGEs may promote colorectal cancer, but prospective epidemiologic studies are inconclusive. We conducted a case-control study nested within a large European cohort. Plasma concentrations of three protein-bound AGEs-Nε-(carboxy-methyl)lysine (CML), Nε-(carboxy-ethyl)lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)-were measured by ultra-performance liquid chromatography-tandem mass spectrometry in baseline samples collected from 1378 incident primary colorectal cancer cases and 1378 matched controls. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression for colorectal cancer risk associated with CML, CEL, MG-H1, total AGEs, and [CEL+MG-H1: CML] and [CEL:MG-H1] ratios. Inverse colorectal cancer risk associations were observed for CML (OR comparing highest to lowest quintile, ORQ5 versus Q1 = 0.40, 95% CI: 0.27-0.59), MG-H1 (ORQ5 versus Q1 = 0.73, 95% CI: 0.53-1.00) and total AGEs (OR Q5 versus Q1 = 0.52, 95% CI: 0.37-0.73), whereas no association was observed for CEL. A higher [CEL+MG-H1: CML] ratio was associated with colorectal cancer risk (ORQ5 versus Q1 = 1.91, 95% CI: 1.31-2.79). The associations observed did not differ by sex, or by tumour anatomical sub-site. Although individual AGEs concentrations appear to be inversely associated with colorectal cancer risk, a higher ratio of methylglyoxal-derived AGEs versus those derived from glyoxal (calculated by [CEL+MG-H1: CML] ratio) showed a strong positive risk association. Further insight on the metabolism of AGEs and their dicarbonyls precursors, and their roles in colorectal cancer development is needed.

Dietary intake of advanced glycation endproducts and risk of hepatobiliary cancers: A multinational cohort study.

Advanced glycation endproducts (AGEs) may contribute to liver carcinogenesis because of their proinflammatory and prooxidative properties. Diet is a major source of AGEs, but there is sparse human evidence on the role of AGEs intake in liver cancer etiology. We examined the association between dietary AGEs and the risk of hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition prospective cohort (n = 450 111). Dietary intake of three AGEs, Nε -[carboxymethyl]lysine (CML), Nε -[1-carboxyethyl]lysine (CEL) and Nδ -[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), was estimated using country-specific dietary questionnaires linked to an AGEs database. Cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations between dietary AGEs and risk of hepatocellular carcinoma (HCC), gallbladder and biliary tract cancers were estimated using multivariable Cox proportional hazard regression. After a median follow-up time of 14.9 years, 255 cases of HCC, 100 cases of gallbladder cancer and 173 biliary tract cancers were ascertained. Higher intakes of dietary AGEs were inversely associated with the risk of HCC (per 1 SD increment, HR-CML  = 0.87, 95% CI: 0.76-0.99, HR-CEL  = 0.84, 95% CI: 0.74-0.96 and HR-MH-G1  = 0.84, 95% CI: 0.74-0.97). In contrast, positive associations were observed with risk of gallbladder cancer (per 1 SD, HR-CML  = 1.28, 95% CI: 1.05-1.56, HR-CEL  = 1.17; 95% CI: 0.96-1.40, HR-MH-G1  = 1.27, 95% CI: 1.06-1.54). No associations were observed for cancers of the intra and extrahepatic bile ducts. Our findings suggest that higher intakes of dietary AGEs are inversely associated with the risk of HCC and positively associated with the risk of gallbladder cancer.

Socioeconomic Determinants of Sodium Intake in Adult Populations of High-Income Countries: A Systematic Review and Meta-Analysis.

BACKGROUND: A poorer quality diet among individuals with low socioeconomic status (SES) may partly explain the higher burden of noncommunicable disease among disadvantaged populations. Because there is a link between sodium intake and noncommunicable diseases, we systematically reviewed the current evidence on the social patterning of sodium intake. OBJECTIVES: To conduct a systematic review and a meta-analysis of the evidence on the association between SES and sodium intake in healthy adult populations of high-income countries. SEARCH METHODS: We followed the PRISMA-Equity guidelines in conducting a literature search that ended June 3, 2016, via MEDLINE, Embase, and SciELO. We imposed no publication date limits. SELECTION CRITERIA: We considered only peer-reviewed articles meeting the following inclusion criteria: (1) reported a measure of sodium intake disaggregated by at least 1 measure of SES (education, income, occupation, or any other socioeconomic indicator); (2) were written in English, Spanish, Portuguese, French, or Italian; and (3) were conducted in a high-income country as defined by the World Bank (i.e., per capita national gross income was higher than $12 746). We also excluded articles that exclusively sampled low-SES individuals, pregnant women, children, adolescents, elderly participants, or diseased patients or that reported results from a trial or intervention. DATA COLLECTION AND ANALYSIS: As summary measures, we extracted (1) the direction (positive, negative, or neutral) and the magnitude of the association between each SES indicator and sodium intake, and (2) the estimated sodium intake according to SES level. When possible and if previously unreported, we calculated the magnitude of the relative difference in sodium intake between high- and low-SES groups for each article, applying this formula: ([value for high-SES group - value for low-SES group]/[value for high-SES group]) × 100. We considered an association significant if reported as such, and we set an arbitrary 10% relative difference as clinically relevant and significant. We conducted a meta-analysis of the relative difference in sodium intake between high- and low-SES groups. We included articles in the meta-analysis if they reported urine-based sodium estimates and provided the total participant numbers in the low- and high-SES groups, the estimated sodium intake means for each group (in mg/day or convertible units), and the SDs (or transformable measures). We chose a random-effects model to account for both within-study and between-study variance. MAIN RESULTS: Fifty-one articles covering 19 high-income countries met our inclusion criteria. Of these, 22 used urine-based methods to assess sodium intake, and 30 used dietary surveys. These articles assessed 171 associations between SES and sodium intake. Among urine-based estimates, 67% were negative (higher sodium intake in people of low SES), 3% positive, and 30% neutral. Among diet-based estimates, 41% were negative, 21% positive, and 38% neutral. The random-effects model indicated a 14% relative difference between low- and high-SES groups (95% confidence interval [CI] = -18, -9), corresponding to a global 503 milligrams per day (95% CI = 461, 545) of higher sodium intake among people of low SES. CONCLUSIONS: People of low SES consume more sodium than do people of high SES, confirming the current evidence on socioeconomic disparities in diet, which may influence the disproportionate noncommunicable disease burden among disadvantaged socioeconomic groups. Public Health Implications. It is necessary to focus on disadvantaged populations to achieve an equitable reduction in sodium intake to a population mean of 2 grams per day as part of the World Health Organization's target to achieve a 25% relative reduction in noncommunicable disease mortality by 2025.

Interventions promoting healthy eating as a tool for reducing social inequalities in diet in low- and middle-income countries: a systematic review.

INTRODUCTION: Diet is a major risk factor for non-communicable diseases (NCDs) and is also strongly patterned by socioeconomic factors. Whether interventions promoting healthy eating reduce social inequalities in diet in low- and middle-income countries (LMICs) remains uncertain. This paper aims to summarize current evidence on interventions promoting healthy eating in LMICs, and to establish whether they reduce social inequalities in diet. METHODS: Systematic review of cross-sectional or quasi-experimental studies (pre- and post-assessment of interventions) in Pubmed, Scielo and Google Scholar databases, including adults in LMICs, assessing at least one outcome of healthy eating and showing results stratified by socioeconomic status. RESULTS: Seven intervention studies including healthy eating promotion, conducted in seven LMICs (Brazil, Chile, Colombia, Iran, Panama, Trinidad and Tobago, and Tunisia), met our inclusion criteria. To promote healthy eating, all interventions used nutrition education and three of them combined nutrition education with improved acces to foods or social support. Interventions targeted mostly women and varied widely regarding communication tools and duration of the nutrition education sessions. Most interventions used printed material, media use or face-to-face training and lasted from 6 weeks to 5 years. Four interventions targeted disadvantaged populations, and three targeted the entire population. In three out of four interventions targeting disadvantaged populations, healthy eating outcomes were improved suggesting they were likely to reduce social inequalities in diet. All interventions directed to the entire population showed improved healthy eating outcomes in all social strata, and were considered as having no impact on social inequalities in diet. CONCLUSION: In LMICs, agentic interventions promoting healthy eating reduced social inequalities in diet when specifically targeting disadvantaged populations. Further research should assess the impact on social inequalities in diet of a combination of agentic and structural approaches in interventions promoting healthy eating.

Lost in translation: dietary management of cardiovascular risk factors is seldom implemented.

OBJECTIVE: To assess dietary management of cardiovascular risk factors (CVRFs) in the general population. METHOD: Cross-sectional study conducted between 2009 and 2012 on 4811 participants (2567 women, 58±11years) living in Lausanne, Switzerland. RESULTS: Sixteen percent of participants diagnosed with overweight/obesity reported a slimming diet. Slimming diet was associated with diagnosis of hypertension: Odds ratio and (95% confidence interval): 0.61 (0.40-0.93); older age [0.84 (0.58-1.21), 0.79 (0.53-1.18) and 0.47 (0.27-0.81) for [50-60[, [60-70[ and [70+ years, respectively]; female gender [1.84 (1.36-2.48)] and diagnosis of diabetes [2.16 (1.13-4.12)]. Only 8% of participants diagnosed with hypertension reported a low-salt diet. Low-salt diet was associated with antihypertensive drug treatment [2.17 (1.28-3.68)] and diagnosis of diabetes [2.72 (1.26-5.86)]. One-third of participants diagnosed with dyslipidemia reported a low-fat diet. Low-fat diet was associated with female gender [1.47 (1.17-1.86)]; older age [1.29 (0.89-1.87), 1.71 (1.18-2.48) and 2.01 (1.33-3.03) for [50-60[, [60-70[ and [70+ years, respectively]; hypolipidemic drug treatment [OR=1.68 (1.29-2.18)]; current smoking [0.70 (0.51-0.96)] and obesity [0.67 (0.45-1.00)]. Approximately half of participants diagnosed with diabetes reported an antidiabetic diet. Antidiabetic diet was associated with current smoking [0.44 (0.22-0.88)] and antidiabetic drug treatment [OR=3.26 (1.81-5.86)]. CONCLUSION: Dietary management of CVRFs is seldom implemented in Switzerland.

Socioeconomic Position, Pre-Obesity and Obesity in Latin American Cities: A Systematic Review.

Currently the socioeconomic gradient of obesity it is not well understood in the urban population in Latin American. This study reviewed the literature assessing associations between pre-obesity, obesity, and socioeconomic position (SEP) in adults living in urban areas in Latin American countries. PubMed and SciELO databases were used. Data extraction was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We extracted data on the association between SEP (e.g., education, income), pre-obesity (body mass index [BMI] ≥ 25 and < 30 kg/m2) and obesity (BMI ≥ 30 kg/m2). Relative differences between low and high SEP groups were assessed and defined a priori as significant at p < 0.05. Thirty-one studies met our inclusion criteria and most were conducted in Brazil and Mexico (22 and 3 studies, respectively). One study presented nonsignificant associations. Forty-seven percent of associations between education or income and pre-obesity were negative. Regarding obesity, 80 percent were negative and 20 percent positive. Most negative associations were found in women while in men they varied depending on the indicator used. Pre-obesity and obesity by SEP did not follow the same pattern, revealing a reversal of the obesity social gradient by SEP, especially for women in Latin America, highlighting the need for articulated policies that target structural and agentic interventions.

Genetically predicted gut bacteria, circulating bacteria-associated metabolites and pancreatic ductal adenocarcinoma: a Mendelian randomisation study.

Pancreatic ductal adenocarcinoma (PDAC) has high mortality and rising incidence rates. Recent data indicate that the gut microbiome and associated metabolites may play a role in the development of PDAC. To complement and inform observational studies, we investigated associations of genetically predicted abundances of individual gut bacteria and genetically predicted circulating concentrations of microbiome-associated metabolites with PDAC using Mendelian randomisation (MR). Gut microbiome-associated metabolites were identified through a comprehensive search of Pubmed, Exposome Explorer and Human Metabolome Database. Single Nucleotide Polymorphisms (SNPs) associated by Genome-Wide Association Studies (GWAS) with circulating levels of 109 of these metabolites were collated from Pubmed and the GWAS catalogue. SNPs for 119 taxonomically defined gut genera were selected from a meta-analysis performed by the MiBioGen consortium. Two-sample MR was conducted using GWAS summary statistics from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including a total of 8,769 cases and 7,055 controls. Inverse variance-weighted MR analyses were performed along with sensitivity analyses to assess potential violations of MR assumptions. Nominally significant associations were noted for genetically predicted circulating concentrations of mannitol (odds ratio per standard deviation [ORSD] = 0.97; 95% confidence interval [CI]: 0.95-0.99, p = 0.006), methionine (ORSD= 0.97; 95%CI: 0.94-1.00, p = 0.031), stearic acid (ORSD= 0.93; 95%CI: 0.87-0.99, p = 0.027), carnitine = (ORSD=1.01; 95% CI: 1.00-1.03, p = 0.027), hippuric acid (ORSD= 1.02; 95%CI: 1.00-1.04, p = 0.038) and 3-methylhistidine (ORSD= 1.05; 95%CI: 1.01-1.10, p = 0.02). Two gut microbiome genera were associated with reduced PDAC risk; Clostridium sensu stricto 1 (OR: 0.88; 95%CI: 0.78-0.99, p = 0.027) and Romboutsia (OR: 0.87; 95%CI: 0.80-0.96, p = 0.004). These results, though based only on genetically predicted gut microbiome characteristics and circulating bacteria-related metabolite concentrations, provide evidence for causal associations with pancreatic carcinogenesis.

Associations between dietary inflammatory scores and biomarkers of inflammation in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

BACKGROUND: Since the first version of the dietary inflammatory index (DII®) developed in the past decade, several other versions have been developed. However, to date no study has attempted to compare these versions with respect to their associations with biomarkers of inflammation. OBJECTIVE: We aimed to investigate the relationship between four dietary inflammatory scores [DII, two energy-adjusted derivatives (E-DII and E-DIIr), and the Inflammatory Score of the Diet (ISD)], and circulating levels of several inflammatory markers and adipokines. METHODS: This study included 17 637 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with at least one marker of inflammation measured in blood. Associations between the four scores and C-reactive protein (CRP), interleukin (IL)6, IL10, IL1RA, tumor necrosis factor-α (TNFα), soluble tumor necrosis factor receptor-1 (sTNFR1), sTNFR2, leptin, soluble leptin receptor (sLeptin R), adiponectin, and High Molecular Weight (HMW) adiponectin were evaluated using multivariable linear regressions adjusted for potential confounders. RESULTS: Positive associations were observed between the four dietary inflammatory scores and levels of CRP, IL6, sTNFR1, sTNFR2 and leptin. However, only the DII and the ISD were positively associated with IL1RA levels and only the DII and the E-DIIr were positively associated with TNFα levels. The proportion of variance of each biomarker explained by the scores was lower than 2%, which was equivalent to the variance explained by smoking status but much lower than that explained by body mass index. CONCLUSIONS: Our results suggest that the four dietary inflammatory scores were associated with some biomarkers of inflammation and could be used to assess the inflammatory potential of diet in European adults but are not sufficient to capture the inflammatory status of an individual. These findings can help to better understand the inflammatory potential of diet, but they need to be replicated in studies with repeated dietary measurements.

Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.

Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: Nε-carboxy-methyllysine (CML), Nε-carboxyethyllysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HRQ5vs.Q1 = 0.92, 95% CI = 0.85-1.00) and MG-H1 (HRQ5vs.Q1 = 0.92, 95% CI = 0.85-1.00), but not for CEL (HRQ5vs.Q1 = 0.97, 95% CI = 0.89-1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development.

Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk: A Case-Control Study Nested within a European Prospective Cohort.

BACKGROUND: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation. METHODS: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively. RESULTS: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; P heterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99). CONCLUSIONS: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk. IMPACT: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.

Large-scale fortification of condiments and seasonings as a public health strategy: equity considerations for implementation.

Fortification of staple foods with vitamins and minerals is an effective approach to increase micronutrient intake and improve nutritional status. The specific use of condiments and seasonings as vehicles in large-scale fortification programs is a relatively new public health strategy. This paper underscores equity considerations for the implementation of large-scale fortification of condiments and seasonings as a public health strategy by examining nonexhaustive examples of programmatic experiences and pilot projects in various settings. An overview of conceptual elements in implementation research and equity is presented, followed by an examination of equity considerations for five implementation strategies: (1) enhancing the capabilities of the public sector, (2) improving the performance of implementing agencies, (3) strengthening the capabilities and performance of frontline workers, (3) empowering communities and individuals, and (4) supporting multiple stakeholders engaged in improving health. Finally, specific considerations related to intersectoral action are considered. Large-scale fortification of condiments and seasonings cannot be a standalone strategy and needs to be implemented with concurrent and coordinated public health strategies, which should be informed by a health equity lens.

Educational differences in dietary intake and compliance with dietary recommendations in a Swiss adult population.

OBJECTIVES: This study assessed the impact of education on diet and compliance with the national recommendations. METHODS: The study included 4338 adult participants of the Colaus study, a cross-sectional, population-based study conducted between 2009 and 2012 in Lausanne (Switzerland). Education was categorized as primary, apprenticeship, secondary, and tertiary. RESULTS: Men with primary vs. tertiary education had a lower intake of monounsaturated fatty acids (29.4 vs. 30.9 g/day), iron (11.4 vs. 11.8 mg/day), vitamin A (758.2 vs. 904.2 retinol equivalents/day), and vitamin D (2.3 vs. 3.0 µg/day). Women with primary vs. tertiary education had a lower intake of monounsaturated fatty acids (25.5 vs. 27.4 g/day), fiber (15.6 vs. 17.2 g/day) and iron (9.8 vs. 10.3 mg/day). Men with primary vs. tertiary education had a better compliance with protein recommendations [odds ratio (95 % CI): 2.31 (1.37; 3.90)], while women with primary vs. tertiary education had a better compliance with vitamin A recommendations [odds ratio 1.74 (1.15; 2.65)]. CONCLUSIONS: Overall, our results do not confirm a unidirectional association between education and diet, and question the approach of targeted interventions alone in selected educational groups to prevent chronic diseases.

Socioeconomic Differences in Dietary Patterns in an East African Country: Evidence from the Republic of Seychelles.

BACKGROUND: In high income countries, low socioeconomic status (SES) is related to unhealthier dietary patterns, while evidence on the social patterning of diet in low and middle income countries is scarce. OBJECTIVE: In this study, we assess dietary patterns in the general population of a middle income country in the African region, the Republic of Seychelles, and examine their distribution according to educational level and income. METHODS: Data was drawn from two independent national surveys conducted in the Seychelles among adults aged 25-64 years in 2004 (n = 1236) and 2013 (n = 1240). Dietary patterns were assessed by principal component analysis (PCA). Educational level and income were used as SES indicators. Data from both surveys were combined as no interaction was found between SES and year. RESULTS: Three dietary patterns were identified: "snacks and drinks", "fruit and vegetables" and "fish and rice". No significant associations were found between SES and the "snacks and drinks" pattern. Low vs. high SES individuals had lower adherence to the "fruit and vegetables" pattern [prevalence ratio (95% CI) 0.71 (0.60-0.83)] but a higher adherence to the traditional "fish and rice" pattern [1.58 (1.32-1.88)]. Income modified the association between education and the "fish and rice" pattern (p = 0.02), whereby low income individuals had a higher adherence to this pattern in both educational groups. CONCLUSION: Low SES individuals have a lower consumption of fruit and vegetables, but a higher consumption of traditional foods like fish and rice. The Seychelles may be at a degenerative diseases stage of the nutrition transition.

Socioeconomic predictors of dietary patterns among Guatemalan adults.

OBJECTIVES: We aimed to assess the associations of socioeconomic factors with dietary patterns in a Guatemalan population. METHODS: Cross-sectional data of 1076 participants (42 % men, mean age 32.6 ± 4.2 years) collected between 2002 and 2004 in four rural villages in Guatemala. Dietary patterns were derived using principal component analysis. Chi-square and Poisson regression models were used to assess associations between socioeconomic factors and dietary patterns. RESULTS: Three dietary patterns were identified: "Western" (high in processed foods), "traditional" (high in traditional foods) and "coffee and sugar", explaining 11, 7 and 6 % of the variance, respectively. Annual expenditures were associated with a higher adherence to the "Western" pattern: prevalence ratios [(PR) (95 % confidence interval)] 1.92 (1.17-3.15) for the highest vs. lowest expenditure group in men and 8.99 (3.57-22.64) in women. A borderline significant (p = 0.06) negative association was found between the "traditional" pattern and higher household expenditures [0.71 (0.49-1.02) in men] and with schooling [0.23 (0.05-1.02)] in women (p = 0.05). CONCLUSIONS: Dietary patterns in Guatemala are predicted by socioeconomic factors. In particular, high annual expenditures are associated with a more westernized, less traditional diet.