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BACKGROUND: Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive.METHODS: We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.RESULTS: Of 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HR Q5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HR Q5vs.Q1:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HR Q5vs.Q1:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HR Q5vs.Q1:1.11, 95%CI:0.94, 1.31), heme (HR Q5vs.Q1:0.95; 95%CI:0.84, 1.07) or non-heme iron (HR Q5vs.Q1:1.03, 95%CI:0.88, 1.20). Substitution of heme with non-heme iron demonstrated lower CRC risk in men (HR:0.94; 95%CI: 0.89, 0.99). CONCLUSIONS: Our findings suggest potential sex-specific CRC risk associations for higher iron consumption that may differ by dietary sources.

RationaleSevere fetal malnutrition has been related to an increased risk of respiratory diseases later in life, but evidence for the association of a suboptimal diet during pregnancy with respiratory outcomes in childhood is conflicting. We aimed to examine whether a pro-inflammatory or low-quality maternal diet during pregnancy was associated with child's respiratory health.MethodsWe performed an individual participant meta-analysis among 18 326 mother–child pairs from seven European birth cohorts. Maternal pro-inflammatory and low-quality diets were estimated by energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) scores. Preschool wheezing and school-age asthma were measured using questionnaires and lung function by spirometry.ResultsAfter adjustment for lifestyle and sociodemographic factors, we observed that a higher maternal E-DII score (a more pro-inflammatory diet) during pregnancy was associated only with a lower forced vital capacity (FVC) in children (z-score difference −0.05, 95% CI −0.08– −0.02, per interquartile range increase). No linear associations of the maternal E-DII or DASH score with child's wheezing or asthma were observed. In an exploratory examination of the extremes, a very low DASH score (ConclusionThe main results from this individual participant data meta-analysis do not support the hypothesis that maternal pro-inflammatory or low-quality diet in pregnancy are related to respiratory diseases in childhood.

International audience; Due to the large number of chemical food contaminants, consumers are exposed simultaneously to a wide range of chemicals which can interact and have a negative impact on health. Nevertheless, due to the multitude of possible chemical combinations it is unrealistic to test all combined toxicological effects. It is therefore essential to identify the most relevant mixtures to which the population is exposed through the diet and investigate their impact on heath. The present study aims to identify and describe the main chemical mixtures to which women enrolled in the E3N study, a large French prospective cohort, are chronically exposed through the diet. 74 522 women who had answered a validated semi-quantitative food frequency questionnaire in 1993, were included in the present study. Dietary exposure to chemical contaminates was estimated based on the food contamination measured in 186 core food in France collected between 2007 and 2009 by the French agency for food, environment and occupational health, and safety (ANSES) in the framework of the second French total diet study (2TDS). The sparse non-negative matrix under-approximation (SNMU) was used to identify mixtures of chemical substances. A k-means clustering classification of the whole study population was then performed to define clusters with similar co-exposure profiles. Overall, 8 mixtures which explained 83% of the total variance, were retained. The first mixture, entitled "Minerals, inorganic contaminants, and furans", explained the highest proportion of the total variance (38%), and was correlated in particular with the consumption of "Offal" (rho = 0.22), "Vegetables except roots" (rho = 0.20), and "Eggs" (rho = 0.19). The other seven mixtures explained between 17% and 1% of the variance. Finally, 5 clusters were identified based on the adherence to the 8 mixtures. This study, being the largest ever conducted to identify dietary exposure to chemical mixtures, represents a concrete attempt to prioritize mixtures for which it is essential to investigate combined health effects based on exposure.

Healthy dietary patterns are recommended for prevention of cardiovascular disease, which remains the leading cause of morbidity and mortality globally. In this review, we discuss dietary patterns that are not only optimal for CVD prevention and management but also sustainable in maximizing health, environmental, and economic benefits. The growing literature on sustainable diets in the context of environmental sustainability includes subtopics of climate change, land use, biodiversity loss, freshwater use, and reactive nitrogen emissions. Similarly, economic sustainability, beyond the retail cost of food, extends to healthcare costs and the economic costs of environmental destruction related to current agricultural practices and food choices. Dietary patterns that are high in plant foods and low in animal foods could maximize health, environmental, and economic benefits; however, questions remain about how to best promote these patterns to achieve wider adoption in an environmentally and economically sustainable way.

Cold- and diet-induced recruitment of brown adipose tissue (BAT) and the browning of white adipose tissue (WAT) are dynamic processes, and the recruited state attained is a state of dynamic equilibrium, demanding continuous stimulation to be maintained. An involvement of macrophages, classical proinflammatory (M1) or alternatively activated anti-inflammatory (M2), is presently discussed as being an integral part of these processes. If these macrophages play a mediatory role in the recruitment process, such an involvement would have to be maintained in the recruited state. We have, therefore, investigated whether the recruited state of these tissues is associated with macrophage accretion or attrition. We found no correlation (positive or negative) between total UCP1 mRNA levels (as a measure of recruitment) and proinflammatory macrophages in any adipose depot. We found that in young chow-fed mice, cold-induced recruitment correlated with accretion of anti-inflammatory macrophages; however, such a correlation was not seen when cold-induced recruitment was studied in diet-induced obese mice. Furthermore, the anti-inflammatory macrophage accretion was mediated via β1/β2-adrenergic receptors; yet, in their absence, and thus in the absence of macrophage accretion, recruitment proceeded normally. We thus conclude that the classical recruited state in BAT and inguinal (brite/beige) WAT is not paralleled by macrophage accretion or attrition. Our results make mediatory roles for macrophages in the recruitment process less likely. NEW & NOTEWORTHY A regulatory or mediatory role—positive or negative—for macrophages in the recruitment of brown adipose tissue is presently discussed. As the recruited state in the tissue is a dynamic process, maintenance of the recruited state would need persistent alterations in macrophage complement. Contrary to this expectation, we demonstrate here an absence of alterations in macrophage complement in thermogenically recruited brown—or brite/beige—adipose tissues. Macrophage regulation of thermogenic capacity is thus less likely.

Background Chad Lake is a central place in a region with a high prevalence of vitamin A deficiency. Spirulina, a natural source of β-carotene, is traditionally produced and eaten as “Dihe” around Chad Lake. β-carotene spirulina has been found to have a high conversion factor to retinol. The aim of the study was to assess if the retinol status between healthy women eating spirulina Dihe daily (SPI+) and not (SPI-) in the Chad Lake area was different. Methods This study was observational: 88 healthy women were recruited and selected according to clinical criteria and their willingness to participate. They were divided in two groups according to their Dihe daily consumption: those who eat Dihe (SPI+; n = 35) and those who do not (SPI-; n = 35). After anthropometric and dietary assessments, blood retinol, β-carotene, retinol binding, and inflammatory/nutritional proteins were measured. Results The diet between groups was identical, except for β-carotene consumption, which was higher in SPI+ than in SPI- (10.8 vs. 1.8 mg/day). The serum retinol and β-carotene concentrations were significantly higher in SPI+ than in SPI- at 1.26 ± 0.36 μmol/l versus 1.03 ± 0.31 μmol/l (p = 0.008) and 0.59 ±0.37 μmol/l versus 0.46± 0.31 μmol/l (p = 0.04), respectively. Seventy-seven percent of SPI+ versus 29% of SPI- had an adequate blood retinol value (p = 0.01). Conclusion The results confirm that β-carotene in spirulina is an effective positive modulator of blood retinol status. Dihe is a potential natural source of β-carotene to achieve a proper vitamin A status in healthy women living near Chad Lake.

Summary Background Human dietary exposure to chemicals can result in a wide range of adverse health effects. Some substances might cause non-communicable diseases, including cancer and coronary heart diseases, and could be nephrotoxic. Food is the main human exposure route for many chemicals. We aimed to assess human dietary exposure to a wide range of food chemicals. Methods We did a total diet study in Benin, Cameroon, Mali, and Nigeria. We assessed 4020 representative samples of foods, prepared as consumed, which covered more than 90% of the diet of 7291 households from eight study centres. By combining representative dietary surveys of countries with findings for concentrations of 872 chemicals in foods, we characterised human dietary exposure. Findings Exposure to lead could result in increases in adult blood pressure up to 2·0 mm Hg, whereas children might lose 8·8–13·3 IQ points (95th percentile in Kano, Nigeria). Morbidity factors caused by coexposure to aflatoxin B1 and hepatitis B virus, and sterigmatocystin and fumonisins, suggest several thousands of additional liver cancer cases per year, and a substantial contribution to the burden of chronic malnutrition in childhood. Exposure to 13 polycyclic aromatic hydrocarbons from consumption of smoked fish and edible oils exceeded levels associated with possible carcinogenicity and genotoxicity health concerns in all study centres. Exposure to aluminium, ochratoxin A, and citrinin indicated a public health concern about nephropathies. From 470 pesticides tested across the four countries, only high concentrations of chlorpyrifos in smoked fish (unauthorised practice identified in Mali) could pose a human health risk. Interpretation Risks characterised by this total diet study underscore specific priorities in terms of food safety management in sub-Saharan Africa. Similar investigations specifically targeting children are crucially needed. Funding Standards and Trade Development Facility.

International audience; The present study explored the anthelmintic effects of condensed tannins (CT) in carob (Ceratonia siliqua) pods fed to sheep against gastrointestinal nematodes. Three independent in vivo trials tested whether i) carob pod (CaBP)-containing feed had an anthelmintic effect and if yes, which was the optimal concentration in the diet; ii) whether this effect could be attributed to tannins through the polyethylene glycol (PEG) test and iii) whether there were any synergistic effects when combined with another tannin-containing feed (e.g. sainfoin). In all trials 6-month old nematode-naive lambs, experimentally infected with both Haemonchus contortus and Trichostrongylus colubriformis, were used. Faecal egg counts (FEC) were performed regularly and at the end of each trial adult worm counts (AWC) and female worm fecundity were recorded. In trial 1, 35 lambs (five groups of seven lambs) were fed different CaBP concentrations ranging from 0% to 12 % w/w. FEC declined up to 39.2 % only in the group fed with 12 %CaBP, while a declining trend (P

Although chemotherapy succeeds in reducing tumor burden, the efficacy is limited due to acquired drug resistance and often irreparable side effects. Studies show that antioxidants may influence the response to chemotherapy and its side effects, although their use remains controversial. The evidence shows that some chemo-drugs induce oxidative stress and lead to normal tissue apoptosis and the entry of cancer cells to a dormant G0 state. Through the suppression of oxidative stress, antioxidants could protect normal cells and bring the tumor out of dormancy so as to expose it to chemotherapies. This review is focused on the redox biology of cancer/normal cells and association of reactive oxygen species with drug resistance, cancer dormancy, and side effects. To this end, evidence from cellular, animal, and clinical studies is provided to better understand the conundrum of dietary antioxidants in cancer chemotherapy.

International audience; Low-density lipoprotein cholesterol (LDL-C) plays a causal role in atherosclerosis. One way to reduce LDL-C levels is to inhibit cholesterol absorption. Plant sterols and stanols compete with cholesterol for absorption in the intestine and induce an average decrease in LDL-C by 5% to 15% in a dose-dependent manner, but not in all individuals. This review focuses on the interindividual variability in response to dietary supplementation with plant sterols and stanols. Dietary plant sterols and stanols have no significant effects on LDL-C in substantial numbers of individuals. Higher responses, in absolute value and percentage of LDL-C, are observed in individuals with higher cholesterol absorption and a lower rate of cholesterol synthesis. Some data provide evidence of the influence of genetics on the response to plant sterols and stanols. Further studies in large populations are required to extend these conclusions about genetic influences.

L’importance de l’alimentation dans de nombreuses maladies inflammatoires chroniques est reconnue par la littérature. Mais qu’en est-il de l’influence de celle-ci sur la santé parodontale ? Les maladies parodontales sont des maladies inflammatoires, dont l’étiologie principale est la plaque bactérienne. Elles constituent un facteur de risque de certaines maladies systémiques telles que les pathologies cardiovasculaires ou encore le diabète. C’est pourquoi il est important de maintenir un état parodontal sain. De plus, un nombre important de facteurs de risque a été identifié comme modifiant la réponse de l’hôte à ces bactéries. L’alimentation, jouant un rôle dans les mécanismes inflammatoires, en fait partie. Elle est devenue un enjeu de santé publique important ainsi qu’un outil marketing central dans l’industrie agro-alimentaire allant jusqu’à modifier les habitudes de consommation des populations. Le but de cette revue narrative est de définir les différents facteurs mis en jeu dans les maladies parodontales ainsi que les constituants de l’alimentation, afin d’établir le lien entre l’alimentation et les maladies parodontales, l’impact des nouvelles tendances émergentes et d’expliquer la manière dont le dentiste pourra conseiller ou utiliser l’alimentation dans le management et le traitement des maladies parodontales.

Through diet, people are chronically exposed to low doses of a large number of contaminants that could exhibit adverse health effects. Toxicological evaluation of food contaminants increases in complexity when the exposure involves chemical mixtures. The aim of this study is to investigate the genotoxic potential, through measuring ©H2AX induction, of six common mixtures of food contaminants to which French adult consumers are chronically exposed. Mixtures were identified by combining information from consumption surveys and contaminant concentration levels in foods. Both single and repeated exposures were evaluated in human liver-derived HepaRG cells. Our results indicated that after a single 24-h exposure, only one mixture induced genotoxicity, and that response occurred at the highest concentration tested. In contrast, we observed after repeated exposures over 3 or 7 days, induction of ©H2AX for all mixtures except one, and a time- and concentration-dependent manner toxicity for four mixtures. Interestingly, we also observed a non-monotonic cytotoxicity concentration-response for one mixture, which might reflect cellular adaptation to the exposure. In conclusion, our study demonstrated that longer-term treatments for in vitro toxicological evaluation, instead of the classical 24 h treatment, may be more relevant regarding human toxicology assessment.

Background: Pregnant women and children are especially vulnerable to exposures to food contaminants, and a balanced diet during these periods is critical for optimal nutritional status. Objectives: Our objective was to study the association between diet and measured blood and urinary levels of environmental contaminants in mother-child pairs from six European birth cohorts (n = 818 mothers and 1,288 children). Methods: We assessed the consumption of seven food groups and the blood levels of organochlorine pesticides, polybrominated diphenyl ethers, polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFAS), and heavy metals and urinary levels of phthalate metabolites, phenolic compounds, and organophosphate pesticide (OP) metabolites. Organic food consumption during childhood was also studied. We applied multivariable linear regressions and targeted maximum likelihood based estimation (TMLE). Results: Maternal high (≥ 4times/week) versus low (< 2times/week) fish consumption was associated with 15% higher PCBs [geometric mean (GM) ratio = 1.15; 95% confidence interval (CI): 1.02, 1.29], 42% higher perfluoroundecanoate (PFUnDA) (GMratio = 1.42; 95% CI: 1.20, 1.68), 89% higher mercury (Hg) (GMratio = 1.89; 95% CI: 1.47, 2.41) and a 487% increase in arsenic (As) (GMratio = 4.87; 95% CI: 2.57, 9.23) levels. In children, high (≥ 3times/week) versus low (< 1.5times/week) fish consumption was associated with 23% higher perfluorononanoate (PFNA) (GMratio = 1.23; 95% CI: 1.08, 1.40), 36% higher PFUnDA (GMratio = 1.36; 95% CI: 1.12, 1.64), 37% higher perfluorooctane sulfonate (PFOS) (GMratio = 1.37; 95% CI: 1.22, 1.54), and >200% higher Hg and As [GMratio = 3.87 (95% CI: 1.91, 4.31) and GMratio = 2.68 (95% CI: 2.23, 3.21)] concentrations. Using TMLE analysis, we estimated that fish consumption within the recommended 2-3 times/week resulted in lower PFAS, Hg, and As compared with higher consumption. Fruit consumption was positively associated with OP metabolites. Organic food consumption was negatively associated with OP metabolites. Discussion: Fish consumption is related to higher PFAS, Hg, and As exposures. In addition, fruit consumption is a source of exposure to OPs. https://doi.org/10.1289/EHP5324. The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 308,333, the Human Early Life Exposome (HELIX) project. The Environment and Childhood (INMA) Sabadell cohort and biomarker measurements were funded by grants from Instituto de Salud Carlos III [Red INMA G03/176; CB06/02/0041; PI041436; PI081151 including Federación Española de Enfermedades Raras (FEDER) funds; PI12/01,890 including FEDER funds; CP13/00,054 including FEDER funds], CIBERESP, Generalitat de Catalunya-Consell Interdepartamental de Recerca i Innovació Tecnològica (CIRIT) 1999SGR 00,241, Generalitat de Catalunya-Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2009 SGR 501, 2014 SGR 822), Fundació La marató de TV3 (090,430), Spanish Ministry of Economy and Competitiveness (SAF2012-32,991 including FEDER funds). The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, National Institutes of Health, National Institute of Neurological Disorders and Stroke (NIH/NINDS; grants UO1 NS 047,537-01 and UO1 NS 047,537-06A1). The Rhea cohort was financially supported by European projects [EU FP6-2003-Food-3-NewGeneris, EU FP6 STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. (project no. 211,250 Escape), EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009-single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. (proposal no. 226,285 ENRIECO), EU- FP7-HEALTH-2012 (proposal no. 308,333 HELIX)] and by the Greek Ministry of Health (Program of Prevention of Obesity and Neurodevelopmental Disorders in Preschool Children, in Heraklion District, Crete, Greece: 2011–2014; “Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–15). The Lithuanian Kaunas Cohort (KANC) supported by the Lithuanian Agency for Science Innovation and Technology (No. 31V-77). M.C. received funding from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (MS16/00,128). E.P. and A.L.B. received funding from the Norwegian Research Council (Project No. 268,465). R.R.C.M. and J.W. were supported by the National Institute for Health Research (NIHR) Collaborations for Leadership in Applied Health Research and Care (CLAHRC) Yorkshire and Humber (IS-CLA-0113-10,020; http://www.clahrc-yh.nihr.ac.uk). L.C. received funding from the NIH (P30ES007048) and National Institute of Environmental Health Sciences (NIEHS R21ES02890).

Summary Facultative animal-bacteria symbioses, which are critical determinants of animal fitness, are largely assumed to be mutualistic. However, whether commensal bacteria benefit from the association has not been rigorously assessed. Using a simple and tractable gnotobiotic model— Drosophila mono-associated with one of its dominant commensals, Lactobacillus plantarum—we reveal that in addition to benefiting animal growth, this facultative symbiosis has a positive impact on commensal bacteria fitness. We find that bacteria encounter a strong cost during gut transit, yet larvae-derived maintenance factors override this cost and increase bacterial population fitness, thus perpetuating symbiosis. In addition, we demonstrate that the maintenance of the association is required for achieving maximum animal growth benefits upon chronic undernutrition. Taken together, our study establishes a prototypical case of facultative nutritional mutualism, whereby a farming mechanism perpetuates animal-bacteria symbiosis, which bolsters fitness gains for both partners upon poor nutritional conditions., Graphical Abstract, Highlights • Symbiotic bacteria hasten the growth of undernourished Drosophila larvae • Without larvae, bacteria rapidly exhaust their nutritional resources and collapse • Larvae secrete maintenance factors allowing bacteria to overcome nutrient shortage • Drosophila larvae/bacteria symbiosis is a case of facultative nutritional mutualism, Storelli et al. describe a mechanism whereby Drosophila larvae maintain their association with beneficial symbiotic bacteria. Symbiotic bacteria hasten the growth of undernourished larvae, while larvae secrete maintenance factors allowing bacteria to persist despite the shortage of their nutritional resources. Thus, Drosophila/bacteria symbiosis is a case of facultative nutritional mutualism.

Fruits and Vegetables (FV) consumption is considered a marker of social inequalities in health since it is considerably decreased in disadvantaged populations. The main objective of this trial was to evaluate the impact of vouchers for FV purchase on the consumption of FV among children living in disadvantaged families in a French urban district. The FLAM study was a controlled randomized intervention trial, performed in Saint-Denis (North suburbs of Paris). The study group (intervention or control) was randomly attributed to parent-child pairs at inclusion. The intervention group received vouchers exchangeable for FV over a 1 year period. Nutritional education through workshops was available for both groups. FV consumption was assessed through face-to-face food frequency questionnaires. Participants who reported eating less than 3.5 FV per day were considered low FV consumers. A total of 92 parent-child pairs were included, in which 45 were allocated to the intervention group and 47 to the control group. Amongst them, 64 completed the final follow-up questionnaire (30% lost to follow-up). After one year, the proportion of low FV consumers in children was significantly lower in the intervention group (29.4%) compared to the control group (66.7%, p = 0.005). Overall, 82% of the vouchers were used by the families. This study found a decreased proportion of small consumers in children after 1 year of distribution of FV vouchers compared to the control group. FV vouchers could be an effective lever to increase FV consumption among children from disadvantaged households. ClinicalTrials.gov identifier no. NCT02461238 .

Introduction : le diabète de type 2 (DT2) est une maladie chronique et répandue. Son traitement repose aussi bien sur la thérapeutique médicamenteuse que sur les mesures hygiéno-diététiques (MHD). Pourtant, l’adhésion à ces mesures reste difficile. Objectif : l’objectif de cette étude était de déterminer les facteurs qui influencent cette adhésion chez des patients DT2 sous antidiabétiques oraux (ADO) suivis en ville, pour améliorer la prise en charge médicale. Méthodes : cette étude qualitative portait sur 20 patients DT2 sous ADO, recrutés par six médecins généralistes d’Ile-de-France. L'identification des facteurs influents reposait sur des entretiens semi-directifs réalisés entre décembre 2015 et décembre 2016. Résultats : les principaux facteurs identifiés sont : le sexe, l’âge, le niveau d’étude, les finances, l'activité professionnelle, le soutien de l'entourage, les antécédents familiaux de diabète, les facteurs de risques cardiovasculaires associés, les comorbidités, le nombre de traitements, l’IMC, l’état psychologique, la connaissance du diabète, ses objectifs, son vécu, son mode de diagnostic et les habitudes alimentaires. Mais ces critères ne semblent pas influer de la même façon sur les différentes MHD (perte de poids, alimentation structurée, activité physique). Ainsi, il semble apparaître des profils de patients : les observants mais ignorants, les malades peu impliqués, les travailleurs renseignés, les stressés peu compliants et les atypiques. Conclusion : plusieurs facteurs semblent influencer l’adhésion aux MHD des patients DT2. L'identification de profils de patients permettrait au professionnel de santé d’adapter et simplifier sa prise en charge.

Importance Observational studies suggest that diet is linked to cognitive health. However, the duration of follow-up in many studies is not sufficient to take into account the long preclinical phase of dementia, and the evidence from interventional studies is not conclusive. Objective To examine whether midlife diet is associated with subsequent risk for dementia. Design, Setting, and Participants Population-based cohort study established in 1985-1988 that had dietary intake assessed in 1991-1993, 1997-1999, and 2002-2004 and follow-up for incident dementia until March 31, 2017. Exposures Food frequency questionnaire to derive the Alternate Healthy Eating Index (AHEI), an 11-component diet quality score (score range, 0-110), with higher scores indicating a healthier diet. Main Outcome and Measures Incident dementia ascertained through linkage to electronic health records. Results Among 8225 participants without dementia in 1991-1993 (mean age, 50.2 years [SD, 6.1 years]; 5686 [69.1%] were men), a total of 344 cases of incident dementia were recorded during a median follow-up of 24.8 years (interquartile range, 24.2-25.1 years). No significant difference in the incidence rate for dementia was observed in tertiles of AHEI exposure during 1991-1993, 1997-1999 (median follow-up, 19.1 years), and 2002-2004 (median follow-up, 13.5 years). Compared with an incidence rate for dementia of 1.76 (95% CI, 1.47-2.12) per 1000 person-years in the worst tertile of AHEI (lowest tertile of diet quality) in 1991-1993, the absolute rate difference for the intermediate tertile was 0.03 (95% CI, −0.43 to 0.49) per 1000 person-years and for the best tertile was 0.04 (95% CI, −0.42 to 0.51) per 1000 person-years. Compared with the worst AHEI tertile in 1997-1999 (incidence rate for dementia, 2.06 [95% CI, 1.62 to 2.61] per 1000 person-years), the absolute rate difference for the intermediate AHEI tertile was 0.14 (95% CI, −0.58 to 0.86) per 1000 person-years and for the best AHEI tertile was 0.14 (95% CI, −0.58 to 0.85) per 1000 person-years. Compared with the worst AHEI tertile in 2002-2004 (incidence rate for dementia, 3.12 [95% CI, 2.49 to 3.92] per 1000 person-years), the absolute rate difference for the intermediate AHEI tertile was −0.61 (95% CI, −1.56 to 0.33) per 1000 person-years and for the best AHEI tertile was −0.73 (95% CI, −1.67 to 0.22) per 1000 person-years. In the multivariable analysis, the adjusted hazard ratios (HRs) for dementia per 1-SD (10-point) AHEI increment were not significant as assessed in 1991-1993 (adjusted HR, 0.97 [95% CI, 0.87 to 1.08]), in 1997-1999 (adjusted HR, 0.97 [95% CI, 0.83 to 1.12]), or in 2002-2004 (adjusted HR, 0.87 [95% CI, 0.75 to 1.00]). Conclusions and Relevance In this long-term prospective cohort study, diet quality assessed during midlife was not significantly associated with subsequent risk for dementia.

International audience

Objective: The aim of our study is to identify factors that may influence the diet monitoring in women with gestational diabetes and to evaluate the information and knowledge they have about their disease. We have also considered possible areas for improvement in adherence to diet as part of gestational diabetes. Materials and methods: We conducted a single-center qualitative study in the Port Royal maternity between September and December 2015, using a semi-directive interview with patients for whom gestational diabetes was diagnosed and starting a diet. The goal is both to define the environment in which they live and to analyze their knowledge. A few days later, a second interview was conducted to evaluate the dietary adaptation, detect items affecting the diet monitoring and identify areas for improvement. Results: In our study, the family, social and professional environment had an influence on the diet monitoring, along with the personal experiences and feelings. The link with the cultural and economic environment has not been highlighted. The pregnancy’s specificity has appeared as an important source of motivation. Women respondents had generally good knowledge about gestational diabetes. In order to facilitate the adherence to diet in women, the areas for improvement identified in our study were better acceptability of pregnant women (particularly with gestational diabetes) in society and mainly in the professional world, and the greater involvement of husbands in the pregnancy monitoring. Conclusion: Many factors seem to be involved in the observance of the diet in women with gestational diabetes. Thus, the integration of all these factors to the medical care and the establishment of a more global therapeutic education adapted to the pregnancy could enhance the observance of the diet.; Objectifs : Le but de notre étude est d’identifier les facteurs susceptibles d’influencer le suivi du régime alimentaire chez les femmes présentant un diabète gestationnel, et d’évaluer l’information et les connaissances qu’elles ont sur leur maladie. Nous avons également envisagé des pistes d’amélioration possibles dans l’observance au régime dans le cadre du diabète gestationnel. Matériels et méthodes : Nous avons réalisé une étude qualitative unicentrique à la maternité de Port-Royal entre septembre et décembre 2015, à l’aide d’un entretien semi-directif auprès des patientes pour qui un diabète gestationnel a été diagnostiqué et commençant un régime alimentaire. Le but est de définir l’environnement dans lequel elles vivent et d’analyser leurs connaissances. Un second entretien a été réalisé quelques jours plus tard afin d’évaluer l’adaptation alimentaire, de repérer les éléments ayant impacté le suivi du régime et d’identifier les pistes d’amélioration.Résultats : Dans notre étude, l’environnement familial, social et professionnel a eu une influence sur le suivi du régime, ainsi que le vécu et les ressentis personnels. Le lien avec l’environnement culturel et économique n’a pas été mis en évidence. La spécificité de la grossesse est apparue comme une source de motivation importante. Les femmes interrogées avaient dans l’ensemble de bonnes connaissances sur le diabète gestationnel. Les pistes d’amélioration identifiées dans notre étude afin de faciliter le respect du régime chez les femmes ont été la meilleure acceptabilité des femmes enceintes (a fortiori ayant un diabète gestationnel) dans la société et principalement dans le monde du travail, et l’implication plus importante des conjoints dans le suivi de grossesse. Conclusion : De nombreux facteurs semblent jouer un rôle dans l’observance du régime diététique chez les femmes présentant un diabète gestationnel. Ainsi, l’intégration de l’ensemble de ces facteurs à la prise en charge médicale et la mise en place d’une éducation thérapeutique plus globale adaptée à la grossesse pourraient améliorer l’observance du régime.

International audience; Health-related quality of life (HRQOL) usually improved after kidney transplantation; however, a non-negligible number of patients did not benefit from transplantation in HRQOL. The aims of this cohort study were to describe the evolution of HRQOL in kidney transplant recipients to search for subgroups with distinct time profiles and to investigate these determinants. Three hundred thirty-seven adult patients were followed up from 1 to 36 months after kidney transplantation. Each patient completed repeated HRQOL assessments (median, 5; range, 2-9). K-means for longitudinal data was used to identify homogeneous clusters of HRQOL time profiles obtained for the mental and physical composite scores (MCS and PCS) and for the 8 dimensions of the short-form 36 scale. Covariates associated with these clusters were investigated using random forest analysis. Magnitude and shape of the HRQOL variations over time were investigated using linear regression mixed models. Two longitudinal clusters were identified for the time profiles of PCS and MCS. Patients classified in the higher cluster (ie, 60% of the population) exhibited a steady-state HRQOL, similar on average to the general population, whereas in the lower cluster, PCS and MCS scores were significantly lower than in the general population. Muscular weakness in the first year after transplantation explained 19% of the interpatient variability of PCS 3 months after transplantation, whereas associated with anxiety, it explained 24% of interpatient MCS variability. This work suggests to promote (i) physical rehabilitation programs after transplantation to curb the muscular loss and (ii) systematic attention to the patient's anxiety.

Although experimental studies suggest that fruits, vegetables and legumes may exert protective effects against prostate carcinogenesis through various bioactive compounds such as dietary fibre and antioxidants, epidemiological evidence is lacking. Notably, very few prospective studies have investigated the relationship between legume intake and prostate cancer risk. Our objective was to prospectively investigate the association between fruit, vegetable, tomato products, potatoes and legume intakes and prostate cancer risk. This study included 3313 male participants to the SUpplémentation en VItamines et Minéraux AntioXydants cohort (follow-up: 1994–2007) who completed at least three 24-h dietary records during the first 2 years of follow-up. Associations between tertiles of intake and prostate cancer risk were assessed by multivariate Cox proportional hazards models. After a median follow-up of 12·6 years, 139 incident prostate cancers were diagnosed. An inverse association was observed between prostate cancer risk and tertiles of legume intake (hazard ratio (HR)T3v.T1=0·53; 95 % CI 0·34, 0·85; Ptrend=0·009). This association was maintained after excluding soya and soya products from the legume group (HRT3 v.T1=0·56; 95 % CI 0·35, 0·89; Ptrend=0·02). No association was observed between prostate cancer risk and tertiles of intakes of fruits (Ptrend=0·25), vegetables (Ptrend=0·91), potatoes (Ptrend=0·77) and tomato products (Ptrend=0·09). This prospective study confirms the null association between fruit and non-starchy vegetable intakes and prostate cancer risk observed in most previous cohorts. In contrast, although very few prospective studies have been published on the topic, our results suggest an inverse association between legume intake and prostate cancer risk, supported by mechanistic plausibility. These results should be confirmed by large-scale observational and intervention studies.

International audience; BACKGROUND: In the field of nutritional epidemiology, principal component analysis (PCA) has been used to derive patterns, but the robustness of interpretation might be an issue when the sample size is small. The authors proposed the alternative use of confirmatory factor analysis (CFA) to define such patterns. OBJECTIVE: The aim was to compare dietary patterns derived through PCA and CFA used as equivalent approaches in terms of stability and relevance. DESIGN: PCA and CFA were performed in 2 different studies: the Epidemiological Study on the Genetics and Environment of Asthma 2-France (EGEA2-France; n = 1236) and the Phenotype and Course of Chronic Obstructive Pulmonary Disease study-Spain (n = 274). To check for stability, PCA and CFA were also performed in 2 subsamples from the EGEA2 study (n = 618 and 309). Statistical proprieties were evaluated by 1000 bootstrapped random sets of observations for each of the 4 subsamples. For each random set of observations, the distribution of the factor loading for each pattern was obtained and represented by using box-plots. To check for relevance, partial correlations between different nutrients and the different patterns derived by either PCA or CFA were calculated. RESULTS: With the use of CFA, 2 consistent dietary patterns were derived in each subsample (the Prudent and the Western patterns), whereas dietary factors were less interpretable with the use of PCA (smaller median of factor loadings and higher dispersion), especially for the smallest subsample. Higher correlations were reported among total fiber, vitamins, minerals, and total lipids with patterns derived by using CFA than with patterns derived by using PCA. CONCLUSION: The current study shows that CFA may be a useful alternative to PCA in epidemiologic studies, especially when the sample size is small.

International audience; Selenium, a dietary trace mineral, essential for humans and animals, exerts its effects mainly through its incorporation into selenoproteins. Adequate selenium intake is needed to maximize the activity of selenoproteins, among which glutathione peroxidases have been shown to play a major role in cellular defense against oxidative stress initiated by excess reactive oxygen species. In humans, a low selenium status has been linked to increased risk of various diseases, including heart disease. The main objective of this review is to present current knowledge on the role of selenium in cardiac health. Experimental studies have shown that selenium may exert protective effects on cardiac tissue in animal models involving oxidative stress. Because of the narrow safety margin of this mineral, most interventional studies in humans have reported inconsistent findings. Major determinants of selenium status in humans are not well understood and several nondietary factors might be associated with reduced selenium status. In this review, we discuss recent studies regarding the role of selenoproteins in the cardiovascular system, the effect of dietary intake on selenium status, the impact of selenium status on cardiac health, and the cellular mechanisms that can be involved in the physiological and toxic effects of selenium.

International audience; As shown in most clinical studies dedicated to carotenoids, there is a huge interindividual variability in absorption, and blood and tissue responses, of dietary carotenoids. The recent discovery that several proteins are involved in carotenoid metabolism in humans has prompted a possible explanation for this phenomenon: genetic variants in genes encoding for these proteins may affect their expression or activity, and in turn carotenoid metabolism and carotenoid status. The proteins clearly identified so far are (i) the carotene oxygenases β,β-carotene-15,15'-monooxygenase (BCMO1) and β,β-carotene-9',10'-oxygenase (BCDO2), which are involved in carotenoid cleavage, (ii) scavenger receptor class B type I (SR-BI), cluster determinant 36 (CD36), and Niemann Pick C1-like 1 (NPC1L1), which are involved in carotenoid uptake by cells, and (iii) glutathione S-transferase Pi 1 (GSTP1) and human retinal lutein-binding protein (HR-LBP), which are involved in the transport of xanthophylls in the retina. Other proteins, such as ATP-binding cassette subfamily G member 5 (ABCG5) and the fatty acid-binding proteins (FABPs) are also apparently involved although firmer evidence is still required. A genome-wide association study, as well as several candidate gene association studies, has shown that groups of subjects bearing different alleles in single nucleotide polymorphisms located in or near several of the above-mentioned genes display different blood and/or tissue concentrations of carotenoids. Further studies are needed to identify all the proteins involved in carotenoid metabolism and assess whether other types of genetic variation, e.g. copy number variants and epigenetic modifications, can modulate carotenoid status. One potential application of such research could be personalized dietary guidelines for carotenoids according to individual genetic characteristics.

International audience; The composition and activity of the gut microbiota codevelop with the host from birth and is subject to a complex interplay that depends on the host genome, nutrition, and life-style. The gut microbiota is involved in the regulation of multiple host metabolic pathways, giving rise to interactive host-microbiota metabolic, signaling, and immune-inflammatory axes that physiologically connect the gut, liver, muscle, and brain. A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health.

International audience; Endoplasmic reticulum (ER) stress is proposed as a novel link between elevated fatty acids levels, obesity and insulin resistance in liver and adipose tissue. However, it is unknown whether ER stress also contributes to lipid-induced insulin resistance in skeletal muscle, the major tissue responsible of insulin-stimulated glucose disposal. Here, we investigated the possible role of ER stress in palmitate-induced alterations of insulin action, both in vivo, in gastrocnemius of high-palm diet fed mice, and in vitro, in palmitate-treated C(2)C(12) myotubes. We demonstrated that 8 weeks of high-palm diet increased the expression of ER stress markers in muscle of mice, whereas ex-vivo insulin-stimulated PKB phosphorylation was not altered in this tissue. In addition, exposure of C(2)C(12) myotubes to either tuncamycine or palmitate induced ER stress and altered insulin-stimulated PKB phosphorylation. However, alleviation of ER stress by either TUDCA or 4-PBA treatments, or by overexpressing Grp78, did not restore palmitate-induced reduction of insulin-stimulated PKB phosphorylation in C(2)C(12) myotubes. This work highlights that, even ER stress is associated with palmitate-induced alterations of insulin signaling, ER stress is likely not the major culprit of this effect in myotubes, suggesting that the previously proposed link between ER stress and insulin resistance is less important in skeletal muscle than in adipose tissue and liver.

This study investigates the effect of various dietary saturated fatty acid (SFA) profiles on plasma lipid parameters and tissue fatty acid composition in rats. The experiment was designed to monitor polyunsaturated fatty acids (PUFA) levels, while examining different amounts and types of SFA. Four isocaloric diets were prepared, containing 10-11 mol% of fatty acids (FA) as linoleic acid (LNA) and 2.5 mol% as α-linolenic acid (ALA), leading to an identical and well-balanced LNA/ALA ratio. The initial rapeseed oil/corn oil mixture providing ALA and LNA was enriched with olive oil to prepare the olive oil diet. The butterfat diet was supplemented with butterfat, containing short-chain SFA (C4:0-C10:0, 17 mol% of FA), lauric acid (C12:0, 3.2 mol%), myristic acid (C14:0, 10.5 mol%) and palmitic acid (C16:0, 14.5 mol%). The saturates diet was supplemented with trilaurin, trimyristin and tripalmitin to obtain the same level of lauric, myristic and palmitic acids as the butterfat diet, without the short-chain SFA. The trimyristin diet was enriched with trimyristin only. The results showed that the butterfat diet contributed to specific effects, compared to the olive oil diet and the saturates and trimyristin diets: a decrease in plasma total, LDL- and HDL-cholesterol, higher tissue storage of ALA and LNA, and a higher level of (n-3) highly unsaturated fatty acids in some tissues. This study supports the hypothesis that in diets with identical well-balanced LNA/ALA ratios, short chain SFA may decrease circulating cholesterol and increase tissue polyunsaturated fatty acid content in the rat.

International audience; Excess dietary proteins and "acid ash" diets have been suspected to increase the risk of osteoporosis, but experimental and epidemiological evidence is mixed. We aimed to determine whether the association between protein intake and the overall acid-base equilibrium of the diet (as renal net acid excretion [RNAE] estimate) and fracture risk vary according to calcium intake. During an average of 8.37 +/- 1.73 yr of follow-up, 2408 women reported a fracture (excluding high-impact trauma) among 36,217 postmenopausal women from the E3N prospective study. We used Cox regression models to study the interaction between calcium and, respectively, proteins and RNAE, from the 1993 dietary questionnaire for fracture risk determination, adjusting for potential confounders. There was no overall association between fracture risk and total protein or RNAE. However, in the lowest quartile of calcium (

Susceptibility to sporadic colorectal cancers (CRC) is generally thought to be the sum of complex interactions between environmental and genetic factors, all of which contribute independently, producing only a modest effect on the whole phenomenon. However, to date, most research has concealed the notion of interaction and merely focused on dissociate analyses of risk factors to highlight associations with CRC. By contrast, we have chosen a combinative approach here to explore the joint effects of several factors at a time. Through an association study based on 1,023 cases and 1,121 controls, we examined the influence on CRC risk of environmental factors coanalyzed with combinations of six single nucleotide polymorphisms located in cytochrome P450 genes (c.−163A>C and c.1548T>C in CYP1A2, g.−1293G>C and g.−1053C>T in CYP2E1, c.1294C>G in CYP1B1, and c.430C>T in CYP2C9). Whereas separate analyses of the SNPs showed no effect on CRC risk, three allelic variant combinations were found to be associated with a significant increase in CRC risk in interaction with an excessive red meat consumption, thereby exacerbating the intrinsic procarcinogenic effect of this dietary factor. One of these three predisposing combinations was also shown to interact positively with obesity. Provided that they are validated, our results suggest the need to develop robust combinative methods to improve genetic investigations into the susceptibility to CRC. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1460–7)

Context:In various observational studies, an inverse relation between calcium intake and body weight has been observed. A possible explanation could be an increased calcium excretion through the faeces caused by an increased dietary calcium intake.Objective:To examine whether an increased calcium intake could lead to changes in faecal fat and energy excretion.Design:Four different isocaloric diets with various calcium contents (400, 1200 and 2500 mg from dairy and 1200 mg from calcium carbonate (1200S)) were administered in a crossover design for 7 days each.Subjects:Five healthy men and five healthy women (age=28+/-2, body mass index=24.1+/-0.4, body fat%=25.6+/-2.4) were recruited by local announcement.Measurements:At the end of every intervention period, faecal samples were collected for determination of fat, energy and calcium content, blood samples were obtained for determination of relevant blood parameters; and fat samples were obtained for measurement of the mRNA expression. Furthermore, resting energy expenditure and fat oxidation were measured with the ventilated-hood technique.Results:We observed a non-significant 56% increase in fat excretion (P=0.159) on the 2500 mg diet, compared to the 400 mg diet. The 2500 mg diet significantly reduced the expression of fatty acid synthase (FAS) mRNA (P

International audience; The association between maternal folate intake and risk of nonsyndromic oral clefts has been studied among many populations with conflicting results. The methylenetetrahydrofolate reductase gene (MTHFR) plays a major role in folate metabolism, and several polymorphisms, including C677T, are common in European populations. Data from a French study (1998-2001) let us investigate the roles of maternal dietary folate intake and the MTHFR polymorphism and their interaction on the risk of cleft lip with/without cleft palate (CL/P) and cleft palate only (CP). We used both case-control (164 CL/P, 76 CP, 236 controls; 148, 59, 168 of whom, respectively, had an available genotype) and case-parent (143 CL/P and 56 CP families) study designs and distinguished the role of the child's genotype and maternally mediated effects on risks. This study observed a beneficial effect of mothers' dietary folate intake on their offspring's risk (odds ratio (OR)(< or = 230 microg/day) = ref; for CL/P, OR([230-314 microg/day]) = 0.56, 95% confidence interval = 0.3-0.9, OR(>314 microg/day) = 0.64, 0.4-1.1; for CP, OR([230-314 microg/day]) = 1.15, 0.6-2.2, OR(>314 microg/day) = 0.70, 0.3-1.4). We observed a reduced risk associated with the TT genotype of the child in the case-control analysis (OR(CC) = ref; for CL/P, OR(TT) = 0.54, 0.3-1.1; for CP, OR(TT) = 0.33, 0.1-1.0); this genotype, either fetal or maternal, was not statistically significant in the case-parent analysis. A frequency of TT genotype higher in our control group than previously reported in France can partly explain the risk reduction observed in case-control comparison. Interactions were not statistically significant. Stratified case-parent analysis showed, however, slight heterogeneity in the role of TT genotype according to folate intake. The modest sample size limits this study, which nonetheless provides new estimate of the possible impact of dietary folate intake and MTHFR polymorphism on oral clefts.

International audience; Principal component analysis (PCA) has been used extensively to derive dietary patterns. We proposed to use confirmatory factor analysis (CFA) in the same context as PCA--as a one-step approach--to derive dietary patterns. The first aim of this study was methodologic and was to compare dietary patterns derived with the use of PCA and CFA, used as equivalent one-step approaches. The second aim of this study was to study these patterns in association with individual characteristics and new adult-onset asthma. We included 30,589 French women from the E3N (epidemiologic prospective cohort study of women from the MGEN national insurance plan) with 1177 reported cases of adult-onset asthma between 1993 and 2005. PCA and CFA were used in the same context, on 27 food groups, to derive dietary patterns. Associations between dietary patterns and adult-onset asthma were assessed by Cox proportional hazards models. Whether we used PCA or CFA, 3 similar factors were found and labeled "Prudent," "Western," and "Aperitif." Correlations between patterns derived with the use of PCA and CFA were high. For the "Prudent" and "Aperitif" patterns, we observed comparable patterns in terms of associations with food groups, individual characteristics, and the onset of asthma. For the "Western" patterns, the one derived with the use of CFA was more related to an unhealthy diet than the one derived with the use of PCA, with higher correlations with the food groups "processed meat" (0.73 vs. 0.51) and "dough and pastry" (0.63 vs. 0.40), and negative associations with physical activity and with having parents who were farmers. Regarding associations with adult-onset asthma, a significant positive association was observed for the "Western" pattern derived with the use of CFA [multivariate RR for highest vs. lowest quintile: 1.30 (1.02, 1.67), P-trend: 0.03], whereas no association was reported when using PCA [RR: 1.14 (0.89, 1.47), P-trend: 0.40]. Although quite similar dietary patterns were derived with the use of PCA and CFA, this study supports the alternative use of CFA to PCA for the identification of dietary patterns in epidemiologic studies.

International audience; The administration of prebiotics as oligosaccharides (OS), by acting on intestinal microbiota, could modulate the immune and inflammatory response and represent a new strategy to improve the outcome of bacterial infection. The aim of this study was to determine whether pectin-derived acidic oligosaccharides (pAOS) could modulate the outcome of pulmonary P. aeruginosa (PA) infection in C57BL/6 mice, which develop a Th1 response to PA lung infection. Mice were randomized for 5 weeks to consume a control or a 5% pAOS diet and chronically infected by PA. Resistance to a second PA infection was also analyzed by reinfecting the surviving mice 2 weeks after the first infection. Compared with control mice, mice fed pAOS had reduced mortality (P

The gut microbiota has been implicated in obesity and its progression towards metabolic disease. Dietary interventions that target the gut microbiota have been suggested to improve metabolic health. The aim of the present study was to investigate the effect of interventions withLactobacillus paracaseiF19 or flaxseed mucilage on the gut microbiota and metabolic risk markers in obesity. A total of fifty-eight obese postmenopausal women were randomised to a single-blinded, parallel-group intervention of 6-week duration, with a daily intake of eitherL. paracaseiF19 (9·4 × 1010colony-forming units), flaxseed mucilage (10 g) or placebo. Quantitative metagenomic analysis of faecal DNA was performed to identify the changes in the gut microbiota. Diet-induced changes in metabolic markers were explored using adjusted linear regression models. The intake of flaxseed mucilage over 6 weeks led to a reduction in serum C-peptide and insulin release during an oral glucose tolerance test (PPPFaecalibacteriumspecies. These changes in the microbiota could not explain the effect of flaxseed mucilage on insulin sensitivity. The intake ofL. paracaseiF19 did not modulate metabolic markers compared with placebo. In conclusion, flaxseed mucilage improves insulin sensitivity and alters the gut microbiota; however, the improvement in insulin sensitivity was not mediated by the observed changes in relative abundance of bacterial species.

The Food Standards Agency Nutrient Profiling System (FSA-NPS) constitutes the basis for the Five-Colour Nutrition Label suggested in France to be put on the front-of-pack of food products. At the individual level, a dietary index (FSA-NPS DI) has been derived and validated and corresponds to a weighted mean of all FSA-NPS scores of foods usually consumed by the individual, reflecting the nutritional quality of his/her diet. Our aim was to investigate the association between the FSA-NPS DI and cancer risk in a large cohort. This prospective study included 6435 participants to the SUpplémentation en VItamines et Minéraux AntioXydants cohort (1994–2007) who completed at least six 24 h dietary records during the first 2 years of follow-up. FSA-NPS DI was computed for each subject (higher values representing lower nutritional quality of the diet). After a median follow-up of 12·6 years, 453 incident cancers were diagnosed. Associations were characterised by multivariate Cox proportional hazards models. The FSA-NPS DI was directly associated with overall cancer risk (hazard ratio (HR)for a 1-point increment=1·08 (95 % CI 1·01, 1·15), Ptrend=0·02; HRQ5 v. Q1=1·34 (95 % CI 1·00, 1·81), Ptrend=0·03). This association tended to be more specifically observed in subjects with moderate energy intake (≤median, HRfor a 1-point increment=1·10 (95 % CI 1·01-1·20), Ptrend=0·03). No association was observed in subjects with higher energy intake (Ptrend=0·3). Results were not statistically significant for breast and prostate cancer risks. For the first time, this study investigated the prospective association between the FSA-NPS individual score and cancer risk. The results suggest that unhealthy food choices may be associated with a 34 % increase in overall cancer risk, supporting the public health relevance of developing front-of-pack nutrition labels based on this score.

Etude effectuée dans la cadre du projet: "Biogéochimie et bioaccumulation du méthyle mercure : ses effets sur la santé dans la plaine du Rio Beni (Amazonie bolivienne)"; International audience; Objectives: To report the nutritional status of children aged up to 15 years and their mothers living in a remote Amazonian area of Bolivia, and to study its main social, familial and maternal determinants. Setting: Fifteen Beni River communities located at the foot of the Andes. Design: Cross-sectional survey of riverside populations. All childbearing mothers and their children in the 15 communities were examined. Methods: Information on household production, dietary habits and demography was collected. Individual clinical, anthropometric and parasitological examinations were carried out. Subjects: A total of 631 persons were examined: 171 mothers and 460 children and adolescents aged 0 to 15 years. Results: There were no cases of severe wasting, but 41% of 0-5-year-olds and 36% of 5-10-year-olds were stunted. Among 346 stool specimens examined, 75% were positive for at least one helminth. Diversity of food and quality of diet were satisfactory in 54% of households, but 27% had low diversity scores. Mothers were lighter and shorter than those observed at the national level: 20% had height below 145 cm. Prevalence of anaemia (42%) was also higher. In pre-school children, multivariate analysis indicated a relationship between growth retardation and household factors such as dietary quality, ethnic group and clinical state, but not maternal anthropometry. In contrast, in school-age children and adolescents, growth retardation was related to maternal characteristics. Conclusions: Growth retardation appeared mainly during the weaning period and did not seem to improve thereafter. To ameliorate this situation, an effort should be made to prevent common parasitic and infectious diseases in young children. Follow-up of pregnant mothers during pregnancy and delivery also needs to be reinforced.

Evidence of the benefits of screening for breast cancer using mammography after the age of 50 is considered sufficient. Information on the determinants of compliance to the recommendations on mammography is needed to identify women to which public health messages should be specifically addressed and also to interpret results from epidemiological data in which some breast cancer cases are detected through screening programmes and others are not. The general characteristics and dietary data of French women participating in the E3N cohort study were analysed. Odds ratios of the frequency of non-compliance to recommendations on breast cancer screening were computed in women over and under the age of 50. Non-compliant women over 50 (i.e. never attenders) had a poorer access to physicians and poorer health with regard to specific risk factors even after adjustment for age and educational level. Women who were used to referring to gynaecologists early in life were better attenders later on. Logically, women under 50 who were over-screened, as compared to public health recommendations, had the opposite characteristics. Public health recommendations should be designed specifically according to targeted subgroups of women. Determinants of attendance for screening should be kept in mind in the interpretation of epidemiological studies in which some cases may be over-screened and others not.

In addition to their role in cell cycle progression, new data reveal an emerging role of D-type cyclins in transcriptional regulation and cellular differentiation processes. Using 3T3-L1 cell lines to study adipogenesis, we observed an up-regulation of cyclin D3 expression throughout the differentiation process. Surprisingly, cyclin D3 was only minimally expressed during the initial stages of adipogenesis, when mitotic division is prevalent. This seemingly paradoxical expression led us to investigate a potential cell cycle-independent role for cyclin D3 during adipogenesis. We show here a direct interaction between cyclin D3 and the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma). Our experiments reveal cyclin D3 acts as a ligand-dependent PPARgamma coactivator, which, together with its cyclin-dependent kinase partner, phosphorylates the A-B domain of the nuclear receptor. Overexpression and knockdown studies with cyclin D3 had marked effects on PPARgamma activity and subsequently on adipogenesis. Chromatin immunoprecipitation assays confirm the participation of cyclin D3 in the regulation of PPARgamma target genes. We show that cyclin D3 mutant mice are protected from diet-induced obesity, display smaller adipocytes, have reduced adipogenic gene expression, and are insulin sensitive. Our results indicate that cyclin D3 is an important factor governing adipogenesis and obesity.

International audience; Increased expression of vascular endothelial growth factor (VEGF) contributes to the growth of many tumors by increasing angiogenesis. Although hypoxia is a potent inducer of VEGF, we previously showed that epidermal growth factor receptor amplification and loss of PTEN, both of which can increase phosphatidylinositol-3-kinase (PI3K) activity, increase VEGF expression. Using both adenoviral vectors and a cell line permanently expressing constitutively active myristoylated Akt (myrAkt), we show that activation of Akt, which is downstream of PI3K, increases VEGF expression in vitro and increases angiogenesis in a Matrigel plug assay. Transient transfection experiments using reporter constructs containing the VEGF promoter showed that up-regulation of VEGF by Akt is mediated through Sp1 binding sites located in the proximal promoter. Small interfering RNA directed against Sp1 prevented the induction of VEGF mRNA in response to myrAkt but not to hypoxia. Expression of myrAkt is associated with increased phosphorylation of Sp1 and its increased binding to a probe corresponding to the -88/-66 promoter region. In conclusion, our results indicate that Sp1 is required for transactivation of the VEGF by Akt. Others have proposed that the PI3K/Akt pathway can increase VEGF expression via the hypoxia-inducible factor 1 (HIF-1); however, our results suggest an alternative mechanism can also operate.

International audience; ID-1101 (4-hydroxyisoleucine), an amino acid extracted from fenugreek seeds, exhibits an interesting glucose-dependent insulin-stimulating activity. The present study was undertaken to investigate a possible extrapancreatic effect of ID-1101 on insulin signaling and action besides its previously described insulinotropic action. Insulin-sensitizing effects of ID-1101 were investigated in rat in vivo by three different approaches: 1) using euglycemic hyperinsulinemic clamps in two different rat models of insulin resistance, i.e., Zucker fa/fa rats and rats fed a sucrose-lipid diet; 2) measuring liver and muscle phosphatidylinositol (PI) 3-kinase activity after an acute injection of ID-1101 in normal and insulin-resistant diabetic rats; and 3) after chronic treatment in two rat models of insulin resistance. Euglycemic hyperinsulinemic clamp experiments revealed that ID-1101 can improve insulin resistance through an increase of peripheral glucose utilization rate in sucrose-lipid-fed rats and by decreasing hepatic glucose production in Zucker fa/fa rats. Moreover, we demonstrated that a single injection of ID-1101 activates the PI 3-kinase activity in liver and muscle from normal rats but also in muscle from diabetic rats. Finally, chronic ID-1101 treatment significantly reduced insulinemia in type 2 diabetic rats and reduced the progression of hyperinsulinemia in insulin-resistant obese Zucker fa/fa rats. These findings clearly demonstrate that ID-1101 can reduce insulin resistance through activation of the early steps of insulin signaling in peripheral tissues and in liver. In summary, ID-1101, besides its insulinotropic effect, directly improves insulin sensitivity, making it a potentially very valuable therapeutic agent for diabetes treatment.

Chicken muscle ribosomal protein S6 kinase (S6K1) has been recently characterised and its enzymic activity is regulated by the nutritional and hormonal (insulin) status in vivo. The regulation of S6K1 is still unknown in neonatal chicks. The present study aimed to compare the activation of S6K1 in early-feeding (EF) and 48 h-delayed-feeding (DF) chicks from hatching to 4 d of age. During post-hatching starvation, S6K1 activity remained at the basal level measured in the control-hatched chicks. The maximum S6K1 activity was recorded on the first day of feeding with an increase of about 2·5-fold in the EF and DF chicks (P

Time for primary review 26 days. Scientists and physicians have long been debating the Mediterranean-style diet and the French paradox for coronary heart disease (CHD). However, folksy they sound, these two biogeographic concepts can still be very useful to explain unexpected or controversial medical and scientific data, such as the low mortality rate from CHD in Mediterranean Southern Europe and in France as compared with other European countries. Understanding these concepts may help improve our ability to treat and prevent CHD. Most of the present confusion probably comes from the consistent underestimation by physicians and scientists of the role of nutrition in CHD. This article is not aimed at giving a comprehensive review of these two complex notions, which have to be analyzed in a broad geographic, climatic, agricultural, historical and socioeconomic context. We will only provide a superficial overview, in relation to the epidemiology of CHD. Finally, we will try to introduce the two concepts as a fundamental premise of a new scientific theory on the role of nutrition in CHD, a theory that remains to be fully formulated. ### 2.1 Definition The definition of the Mediterranean-style diet varies according to the particular Mediterranean area that is considered. For instance, the Greek version of the Mediterranean diet is dominated by the consumption of olive oil and by a high consumption of vegetables and fruits [1]. Since antioxidants are common in these foods, an antioxidant action may provide a plausible explanation for the apparent benefits of that diet [1]. According to another version, however, the Mediterranean diet is a non-strict vegetarian diet rich in oleic acid, omega-3 fatty acids, fiber, vitamins of the B group and various antioxidants, but low in saturated and polyunsaturated fat [2]. With that wider definition, the expected benefits for the prevention of CHD go far … * Corresponding author. Laboratoire du Stress Cardiovasculaire et Pathologies Associees, UFR de Medecine et Pharmacie, Domaine de la Merci, 38706 La Tronche, Grenoble, France. Tel.: +33-4-7663-7471; fax: +33-4-7663-7152

International audience; Background: The level of evidence regarding the association between red and processed meat intakes and breast cancer risk is still low, due to insufficient prospective studies. Moreover, mechanistic data suggest that some antioxidants may modulate this relationship but epidemiological evidence is lacking. Our objectives were to investigate relationships between red and processed meat intakes and breast cancer risk, and to study whether an antioxidant supplementation modulates these associations, which, to our knowledge, has never been investigated before. Methods: The SU.VI.MAX study was a randomized, double-blind, placebo-controlled trial in which participants received a combination of low-dose antioxidants or a placebo from 1994 to 2002. This observational prospective analysis included 4684 women among whom 190 developed a first incident breast cancer between 1994 and 2007 [mean (range) follow-up = 11.3 (0-13) years]. Baseline dietary data were assessed by repeated dietary records in 1994-1995. Associations between quartiles of red and processed meat intakes and breast cancer risk were characterized by multivariate Cox proportional hazards models. Results: Breast cancer risk was directly associated with processed meat intake [ hazard ratio (HR)(Q4vsQ1) = 1.45 (0.92-2.27), P-trend = 0.03] and this association was stronger when excluding cooked ham [HRQ4vsQ1 = 1.90 (1.18-3.05), P-trend = 0.005]. In stratified analyses, processed meat intake was directly associated with breast cancer risk in the placebo group only [HRQ4vsQ1 = 2.46 (1.28-4.72), P-trend = 0.001], but not in the supplemented group [HRQ4vsQ1 = 0.86 (0.45-1.63), P-trend = 0.7]. Conclusion: Processed meat intake was prospectively associated with increased breast cancer risk. This study also suggests that antioxidants may modulate this association by counteracting the potential pro-carcinogenic effects of processed meat on breast cancer.

There is some evidence that environmental factors cause ulcerative colitis. The incidence of ulcerative colitis has increased dramatically between World War II and the 1980s.1 More recent data show that, in several areas, ulcerative colitis incidence decreases.2 3 Such large fluctuations are not consistent with a purely genetic disease, although the increased incidence could be attributed to a better recognition of the disease (coinciding with progress in endoscopy) and the recent decline, to a diagnostic transfer from ulcerative colitis to Crohn’s disease. Migrant studies have shown that ulcerative colitis incidence is at least as high in subjects originating from South Asia living in UK than in native British subjects,4 and has increased recently,5 thus suggesting that the British way of life increases the incidence of ulcerative colitis in migrants from Asia. Another evidence for the role of environment in ulcerative colitis comes from twin studies: disease concordance in monozygotic twins is only 19% in ulcerative colitis, as opposed to 50% in Crohn’s disease.6 Ulcerative colitis is more frequent in non-smokers or ex-smokers than in current smokers, and in patients who have no history of appendectomy for appendicitis. Other environmental factors are likely to contribute to ulcerative colitis pathogenesis. For unexplained reasons, the variability of geographic distribution is lower for ulcerative colitis than for Crohn’s disease.7 However, geographic distributions of …

The role of dietary factors in the aetiology of different types of cancer is increasingly accepted, although few associations have been reported consistently. One of the bottlenecks of studies focusing on dietary factors is due to the limitations of the methodology used to estimate dietary intake. The choice of one method or another depends not only on the type of information sought but also on the practicality of the method. For large cohorts, a self-administered questionnaire seems the most convenient method when aiming at a description of habitual diet. Although French studies1–3 have been collecting information on food consumption using interviews or food diaries, no self-administered French food questionnaire was available which could be used to gather information from a large number of subjects. A dietary history questionnaire was therefore especially developed for use in a large French cohort study, called E3N (Etude Epidemiologique aupres de Femmes de l’Education Nationale), with 103 809 volunteers who agreed to participate from 1990, and which is part of the European Prospective Investigation into Cancer and Nutrition (EPIC).4 Since it concerns a prospective study on nutrition and cancer for which hypotheses are still open, the questionnaire was designed with the aim of collection of information on all possible foods consumed, avoiding oversimplification of food description and identification typical of short food frequency questionnaires. The objective of the present study was to test the accuracy of food intake assessment by the French dietary history questionnaire in order to determine whether the questionnaire is reliable and valid for ranking individuals by dietary and nutrient intake.

International audience; Long-chain polyunsaturated fatty acids (LC-PUFAs) of the n6 (ω6) and n3 series are essential for the development of a child's brain. Fetal LC-PUFA exposure as well as infant exposure via breast milk depend on the maternal intake of these LC-PUFAs and of their respective dietary precursors (PUFAs). We aimed to investigate the associations between maternal LC-PUFA and PUFA [(LC)PUFA] dietary intake during pregnancy and child neurodevelopment at ages 2 and 3 y. In 1335 mother-child pairs from the EDEN cohort, we evaluated associations between daily maternal (LC)PUFA intake during the last 3 months of pregnancy with the child's language at age 2 y and with different assessments of development at age 3 y. Associations were investigated separately in breastfed and never-breastfed children. We examined interactions between the ratios of n6 and n3 (LC)PUFA intakes (n6:n3 fatty acid ratio) and duration of breastfeeding. Breastfeeding mothers had a lower n6:n3 fatty acid ratio (8.4 vs. 8.8; P = 0.02). Among never-breastfed children (n = 338), we found negative associations between maternal dietary n6:n3 fatty acid ratios and neurodevelopment, as reflected by the child's language at age 2 y (β ± SE = -2.1 ± 0.7; P = 0.001) and development assessed with the Ages and Stages Questionnaire at age 3 y (-1.5 ± 0.8; P = 0.05). Among mothers with a high n6:n3 fatty acid ratio only, breastfeeding duration was positively associated with language at age 2 y (P-interaction < 0.05). This suggests that the ratio between maternal dietary n6 and n3 (LC)PUFA intake possibly influences the child's brain development during fetal life but not during or by breastfeeding. However, breastfeeding might compensate for prenatal imbalance in maternal dietary n6:n3 fatty acid ratio.

International audience; Long-chain polyunsaturated fatty acids (LC-PUFAs) of the n6 (ω6) and n3 series are essential for the development of a child's brain. Fetal LC-PUFA exposure as well as infant exposure via breast milk depend on the maternal intake of these LC-PUFAs and of their respective dietary precursors (PUFAs). We aimed to investigate the associations between maternal LC-PUFA and PUFA [(LC)PUFA] dietary intake during pregnancy and child neurodevelopment at ages 2 and 3 y. In 1335 mother-child pairs from the EDEN cohort, we evaluated associations between daily maternal (LC)PUFA intake during the last 3 months of pregnancy with the child's language at age 2 y and with different assessments of development at age 3 y. Associations were investigated separately in breastfed and never-breastfed children. We examined interactions between the ratios of n6 and n3 (LC)PUFA intakes (n6:n3 fatty acid ratio) and duration of breastfeeding. Breastfeeding mothers had a lower n6:n3 fatty acid ratio (8.4 vs. 8.8; P = 0.02). Among never-breastfed children (n = 338), we found negative associations between maternal dietary n6:n3 fatty acid ratios and neurodevelopment, as reflected by the child's language at age 2 y (β ± SE = -2.1 ± 0.7; P = 0.001) and development assessed with the Ages and Stages Questionnaire at age 3 y (-1.5 ± 0.8; P = 0.05). Among mothers with a high n6:n3 fatty acid ratio only, breastfeeding duration was positively associated with language at age 2 y (P-interaction < 0.05). This suggests that the ratio between maternal dietary n6 and n3 (LC)PUFA intake possibly influences the child's brain development during fetal life but not during or by breastfeeding. However, breastfeeding might compensate for prenatal imbalance in maternal dietary n6:n3 fatty acid ratio.

International audience; BACKGROUND: It has been suggested that dietary patterns are associated with future risk of depressive symptoms. However, there is a paucity of prospective data that have examined the temporality of this relation. OBJECTIVE: We examined whether adherence to a healthy diet, as defined by using the Alternative Healthy Eating Index (AHEI), was prospectively associated with depressive symptoms assessed over a 5-y period. DESIGN: Analyses were based on 4215 participants in the Whitehall II Study. AHEI scores were computed in 1991-1993 and 2003-2004. Recurrent depressive symptoms were defined as having a Center for Epidemiologic Studies Depression Scale score ≥16 or self-reported use of antidepressants in 2003-2004 and 2008-2009. RESULTS: After adjustment for potential confounders, the AHEI score was inversely associated with recurrent depressive symptoms in a dose-response fashion in women (P-trend < 0.001; for 1 SD in AHEI score; OR: 0.59; 95% CI: 0.47, 0.75) but not in men. Women who maintained high AHEI scores or improved their scores during the 10-y measurement period had 65% (OR: 0.35%; 95% CI: 0.19%, 0.64%) and 68% (OR: 0.32%; 95% CI: 0.13%, 0.78%) lower odds of subsequent recurrent depressive symptoms than did women who maintained low AHEI scores. Among AHEI components, vegetable, fruit, trans fat, and the ratio of polyunsaturated fat to saturated fat components were associated with recurrent depressive symptoms in women. CONCLUSION: In the current study, there was a suggestion that poor diet is a risk factor for future depression in women.

International audience; OBJECTIVES:We aimed to estimate, in a large French cohort of middle-aged adults derived from the Supplémentation en Vitamines et Minéraux Antioxydants trial, the association of compliance with the guidelines of the French Nutrition and Health Program (PNNS) assessed at inclusion and change in health-related quality of life (HRQoL) over 12 years. A secondary objective was to identify the relative contribution of diet and physical activity to long-term change in HRQoL.DESIGN/SUBJECTS:Subjects were Supplémentation en Vitamines et Minéraux Antioxydants trial participants aged 45 to 60 years at inclusion in the cohort.MAIN OUTCOME MEASURES:Compliance with nutrition guidelines (diet and physical activity) was assessed by the PNNS Guideline Score (maximum 15 points) at inclusion. HRQoL was measured by the Medical Outcomes Survey Short Form 36 (SF-36) at 1 year (initial measurement) and 13 years (final measurement) after inclusion. The primary end point was change in the SF-36 physical component summary (PCS) and mental component summary (MCS) scores over 12 years.RESULTS:In total, 3,005 subjects (mean age 51.4 ± 4.3 years) completed the SF-36 at the initial and final measurement. The mean PNNS Guideline Score was 7.8 ± 1.9 and the mean PCS and MCS was 52.2 ± 6.4 and 50.3 ± 7.0, respectively, at the initial measurement and 48.0 ± 9.6 and 51.2 ± 8.7 at the final measurement. Better compliance with nutritional guidelines was associated with better initial and final HRQoL but not associated with change in HRQoL. Compliance with dietary guidelines was associated with positive change in PCS score but not associated with initial PCS score. In contrast, compliance with dietary guidelines was related to positive initial MCS score but not related to change in MCS score. Compliance with physical activity guidelines was related to initial PCS and MCS scores but not related to change in PCS and MCS scores.CONCLUSIONS:Following physical activity guidelines may be associated with better concomitant HRQoL and following dietary guidelines with better future physical HRQoL.

International audience; BACKGROUND: It has been suggested that dietary patterns are associated with future risk of depressive symptoms. However, there is a paucity of prospective data that have examined the temporality of this relation. OBJECTIVE: We examined whether adherence to a healthy diet, as defined by using the Alternative Healthy Eating Index (AHEI), was prospectively associated with depressive symptoms assessed over a 5-y period. DESIGN: Analyses were based on 4215 participants in the Whitehall II Study. AHEI scores were computed in 1991-1993 and 2003-2004. Recurrent depressive symptoms were defined as having a Center for Epidemiologic Studies Depression Scale score ≥16 or self-reported use of antidepressants in 2003-2004 and 2008-2009. RESULTS: After adjustment for potential confounders, the AHEI score was inversely associated with recurrent depressive symptoms in a dose-response fashion in women (P-trend < 0.001; for 1 SD in AHEI score; OR: 0.59; 95% CI: 0.47, 0.75) but not in men. Women who maintained high AHEI scores or improved their scores during the 10-y measurement period had 65% (OR: 0.35%; 95% CI: 0.19%, 0.64%) and 68% (OR: 0.32%; 95% CI: 0.13%, 0.78%) lower odds of subsequent recurrent depressive symptoms than did women who maintained low AHEI scores. Among AHEI components, vegetable, fruit, trans fat, and the ratio of polyunsaturated fat to saturated fat components were associated with recurrent depressive symptoms in women. CONCLUSION: In the current study, there was a suggestion that poor diet is a risk factor for future depression in women.