Dietary exposure to acrylamide and breast cancer risk: results from the NutriNet-Santé cohort.

BACKGROUND: Acrylamide is classified as a probable human carcinogen by the International Agency for Research on Cancer but epidemiologic evidence on the carcinogenicity of acrylamide from dietary sources is limited. OBJECTIVES: This study aimed to investigate the associations between dietary acrylamide and breast cancer risk in the NutriNet-Santé cohort, accounting for menopausal and hormone receptor status. METHODS: This prospective cohort study included 80,597 French females (mean ± SD age at baseline: 40.8 ± 14 y) during a mean ± SD follow-up of 8.8 ± 2.3 y. Acrylamide intake was evaluated using repeated 24-h dietary records (n ± SD = 5.5 ± 3.0), linked to a comprehensive food composition database. Associations between acrylamide intake and breast cancer risk (overall, premenopausal, and postmenopausal) were assessed by Cox hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors). RESULTS: The mean ± SD dietary acrylamide intake was 30.1 ± 21.9 µg/d (main contributors: coffee, potato fries and chips, pastries, cakes, bread). During follow-up, 1016 first incident breast cancer cases were diagnosed (431 premenopausal, 585 postmenopausal). A borderline significant positive association was observed between dietary acrylamide exposure and breast cancer risk overall (HR for quartile 4 compared with 1: 1.21; 95% CI: 1.00, 1.47) and a positive association was observed with premenopausal cancer (HRQ4vs.Q1: 1.40; 95% CI: 1.04, 1.88). Restricted cubic spline analyses suggested evidence for nonlinearity of these associations, with higher HRs for intermediate (quartile 2) and high (quartile 4) exposures. Receptor-specific analyses revealed positive associations with estrogen receptor-positive breast cancer (total and premenopausal). Acrylamide intake was not associated with postmenopausal breast cancer. CONCLUSIONS: Results from this large prospective cohort study suggest a positive association between dietary acrylamide and breast cancer risk, especially in premenopausal females, and provide new insights that support continued mitigation strategies to reduce the content of acrylamide in food.This trial was registered at clinicaltrials.gov as NCT03335644.

Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism.

OBJECTIVES: Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome's functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation. DESIGN: We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice. RESULTS: Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration. CONCLUSION: Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity. TRIAL REGISTRATION NUMBER: NCT02059538.

Plasma Metabolomics for Discovery of Early Metabolic Markers of Prostate Cancer Based on Ultra-High-Performance Liquid Chromatography-High Resolution Mass Spectrometry.

BACKGROUND: The prevention and early screening of PCa is highly dependent on the identification of new biomarkers. In this study, we investigated whether plasma metabolic profiles from healthy males provide novel early biomarkers associated with future risk of PCa. METHODS: Using the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, we identified plasma samples collected from 146 PCa cases up to 13 years prior to diagnosis and 272 matched controls. Plasma metabolic profiles were characterized using ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). RESULTS: Orthogonal partial least squares discriminant analysis (OPLS-DA) discriminated PCa cases from controls, with a median area under the receiver operating characteristic curve (AU-ROC) of 0.92 using a 1000-time repeated random sub-sampling validation. Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) identified the top 10 most important metabolites (p < 0.001) discriminating PCa cases from controls. Among them, phosphate, ethyl oleate, eicosadienoic acid were higher in individuals that developed PCa than in the controls during the follow-up. In contrast, 2-hydroxyadenine, sphinganine, L-glutamic acid, serotonin, 7-keto cholesterol, tiglyl carnitine, and sphingosine were lower. CONCLUSION: Our results support the dysregulation of amino acids and sphingolipid metabolism during the development of PCa. After validation in an independent cohort, these signatures may promote the development of new prevention and screening strategies to identify males at future risk of PCa.

Diet-Related Metabolomic Signature of Long-Term Breast Cancer Risk Using Penalized Regression: An Exploratory Study in the SU.VI.MAX Cohort.

BACKGROUND: Diet has been recognized as a modifiable risk factor for breast cancer. Highlighting predictive diet-related biomarkers would be of great public health relevance to identify at-risk subjects. The aim of this exploratory study was to select diet-related metabolites discriminating women at higher risk of breast cancer using untargeted metabolomics. METHODS: Baseline plasma samples of 200 incident breast cancer cases and matched controls, from a nested case-control study within the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, were analyzed by untargeted LC-MS. Diet-related metabolites were identified by partial correlation with dietary exposures, and best predictors of breast cancer risk were then selected by Elastic Net penalized regression. The selection stability was assessed using bootstrap resampling. RESULTS: 595 ions were selected as candidate diet-related metabolites. Fourteen of them were selected by Elastic Net regression as breast cancer risk discriminant ions. A lower level of piperine (a compound from pepper) and higher levels of acetyltributylcitrate (an alternative plasticizer to phthalates), pregnene-triol sulfate (a steroid sulfate), and 2-amino-4-cyano butanoic acid (a metabolite linked to microbiota metabolism) were observed in plasma from women who subsequently developed breast cancer. This metabolomic signature was related to several dietary exposures such as a "Western" dietary pattern and higher alcohol and coffee intakes. CONCLUSIONS: Our study suggested a diet-related plasma metabolic signature involving exogenous, steroid metabolites, and microbiota-related compounds associated with long-term breast cancer risk that should be confirmed in large-scale independent studies. IMPACT: These results could help to identify healthy women at higher risk of breast cancer and improve the understanding of nutrition and health relationship.

Association of diet quality and physical activity with healthy ageing in the French NutriNet-Santé cohort.

A growing number of studies have explored overall health during ageing in a holistic manner by investigating multidimensional models of healthy ageing (HA). However, little attention has been given to the role of adherence to national nutrition guidelines in that context. This study aimed to investigate the prospective association between adherence to the French nutrition guidelines and HA. The authors analysed data from 21 407 participants of the NutriNet-Santé study with a median baseline age of 55·6 years (2009-2014) and initially free of major chronic diseases. HA was defined as not developing major chronic disease, no depressive symptoms, no function-limiting pain, independence in instrumental activities of daily living, good physical, cognitive and social functioning, as well as good self-perceived health. Adherence to guidelines of the French Nutrition and Health Programme (Programme National Nutrition Santé or PNNS) was measured via the PNNS Guideline Score (PNNS-GS), using baseline data from repeated 24-h dietary records and physical activity questionnaires. After a median follow-up of 5·7 years, 46·3 % of participants met our HA criteria. Robust-error-variance Poisson regression revealed that higher PNNS-GS scores, reflecting higher adherence to nutrition recommendations (including both diet and physical activity guidelines), were associated with a higher probability to age healthily (relative riskquartile 4 v. quartile 1 = 1·17 (95 % CI 1·12, 1·22)). Supplementary analyses revealed that this association may, to a small part, be mediated by weight status. The results suggest that high adherence to the French national nutrition recommendations may be linked to better overall health throughout ageing.

Estimating sodium intake from spot urine samples at population level: a validation and application study in French adults.

The aim of this study was to assess the validity of the predictive INTERSALT equation using spot urine samples to estimate 24-h urinary Na (24-hUNa) excretion and daily Na intake among the French adult population. Among 193 French adults ('validation sample'), we assessed the validity by comparing predicted 24-hUNa excretion from spot urine and measured 24-hUNa excretion from 24-h urine collections. Spearman correlation coefficients and Bland-Altman plots were used and we calculated calibration coefficients. In a nationally representative sample of 1720 French adults ('application sample'), the calibrated predictive equation was then applied to the spot urine Na values to estimate 24-hUNa excretion and daily Na intake. In that sample, predicted Na intake was compared with that estimated from 24-h dietary recalls. Results were adjusted and corrected using calibration coefficients. In the validation sample, the measured 24-hUNa excretion was on average 14 % higher than the predicted 24-hUNa (+13 % for men and +16 % for women). Correlation between measured and predicted 24-hUNa excretion was moderate (Spearman r 0·42), and the Bland-Altman plots showed underestimation at lower excretion level and overestimation at higher level. In the application study, estimated daily salt intake was 8·0 g/d using dietary recalls, 8·1 g/d using predicted INTERSALT equation and 9·3 g/d after applying calibration coefficients calculated in the validation study. Despite overall underestimation of 24-hUNa excretion by spot urinary Na, the use of predictive INTERSALT equation remains an acceptable alternative in monitoring global Na intake/excreted in the French population but its use is not advised at the individual level.

Saturated, mono- and polyunsaturated fatty acid intake and cancer risk: results from the French prospective cohort NutriNet-Santé.

PURPOSE: Lipid intakes such as saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids have been widely studied regarding cardiovascular health, but their relevance to cancer is unclear. Inconsistent epidemiological results may be explained by varied mechanisms involving PUFAs and redox balance, inflammatory status and cell signalling, along with interactions with other dietary components such as antioxidants, dietary fibre and more generally fruits and vegetable intakes. Therefore, this study aimed to investigate the associations between lipid intakes and cancer risk, and their potential modulation by vitamin C, vitamin E, dietary fibre and fruit and vegetable intakes. METHODS: This prospective study included 44,039 participants aged ≥ 45 years from the NutriNet-Santé cohort (2009-2017). Dietary data were collected using repeated 24 h-dietary records. Multivariable Cox models were performed to characterize associations. RESULTS: SFA intake was associated with increased overall [n = 1722 cases, HRQ5vsQ1 = 1.44 (1.10-1.87), p-trend = 0.008] and breast [n = 545 cases, HRQ5vsQ1 = 1.98 (1.24-3.17), p-trend = 0.01] cancer risks. n-6 PUFA [HRQ5vsQ1 = 0.56 (0.32-0.97), p-trend = 0.01] and MUFA (HRQ5vsQ1 = 0.41 [0.18-0.0.95), p-trend = 0.009] intakes were associated with a decreased risk of digestive cancers (n = 190 cases). Associations between n-6 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes and digestive cancer risk were modulated by dietary fibre, vitamin C and fruit and vegetable intakes. CONCLUSION: These findings suggested that SFA intake could increase overall and breast cancer risks while some unsaturated fatty acids could decrease digestive cancer risk. However, in line with mechanistic hypotheses, our results suggest that intakes of fruits and vegetables and their constituents (antioxidants, fibre) may interact with PUFAs to modulate these associations.

Quantitative assessment of dietary supplement intake in 77,000 French adults: impact on nutritional intake inadequacy and excessive intake.

BACKGROUND: Dietary supplements (DS) are largely consumed in Western countries without demonstrating their nutritional benefits and safety in the general population. The aims, in a large population-based study of French adults, were: (1) to compare the prevalence of nutrient intake inadequacy and the proportion of individuals exceeding tolerable upper intake levels (UL) between DS users and non-users, and (2) to quantify the extent of potentially "at-risk" DS use practices (e.g., DS/drugs contraindicated association or use of beta-carotene DS in smokers). METHODS: 76,925 participants, 47.6% men and 52.4% women, mean age 46.9 ± 16.3 years were enrolled to the NutriNet-Santé cohort and they completed a quantitative DS questionnaire and three 24 h dietary records. A composition database including > 8000 DS was developed. Variance reduction was applied to estimate usual intakes and analyses were weighted according to the French census data. RESULTS: Among DS users of the specific nutrient, DS contributed to 41% of total intake for vitamin D in men, 55% in women; and to 20% of total intake for pyridoxine in men, 21% in women. Compared to dietary intakes only, their prevalence of inadequacy was reduced by 11% for vitamin C, 9% for magnesium, 6% for pyridoxine in men, and 19% for calcium, 12% for iron, and 11% for magnesium in women (p < 0.0001). The proportion of subjects exceeding UL reached 6% for iron and 5% for magnesium in men, and 9% for iron in women. 6% of DS users had potentially "at-risk" practices. CONCLUSION: While DS use contributed to decrease the prevalence of insufficient intake for several nutrients, it also conveyed excessive intake of iron and magnesium. Besides, a substantial proportion of potentially "at-risk" DS use practices was reported.

Unsaturated Fatty Acid Intakes During Midlife Are Positively Associated with Later Cognitive Function in Older Adults with Modulating Effects of Antioxidant Supplementation.

Background: Given the drastic demographic changes characterized as "population aging," the disease burden related to dementia is a major public health problem. The scientific literature documenting the link between mono- and polyunsaturated fatty acids (MUFAs, PUFAs) and cognitive function during aging is plentiful, but findings are inconsistent. Objectives: We aimed to evaluate the association between intakes of unsaturated fatty acids at midlife and cognitive performance 13 y later in French adults, and to test for a modulating effect of antioxidant supplementation. Methods: Fatty acid intakes were estimated with the use of repeated 24-h records (1994-1996) among 3362 subjects (mean ± SD age: 65.5 ± 4.6 y) of the SU.VI.MAX (Supplementation with Antioxidant Vitamins and Minerals) study, including an intervention phase (1994-2002) during which participants were randomly assigned to an "antioxidant supplementation" or placebo group. Cognitive performance was assessed at follow-up only (in 2007-2009) via a battery of 6 standardized neuropsychological tests. A global cognitive score was calculated as the sum of T-scores of the 6 tests. Multivariable-adjusted regression analyses were performed to provide regression coefficients and 95% CIs. Results: In multivariable models, total MUFAs, total PUFAs, and n-6 PUFAs (ω-6 PUFAs) were positively associated with overall cognitive functioning. n-3 PUFA (ω-3 PUFA) intakes showed positive associations among supplemented participants only (mean difference Tertile3 versus Tertile1: 1.40; 95% CI: 0.30, 2.51; P-trend = 0.01, P-interaction = 0.01). A detrimental role of arachidonic acid for cognitive functioning was only detected in the placebo group (mean difference Tertile3 versus Tertile1: -1.38; 95% CI: -2.57, -0.18; P-trend = 0.02, P-interaction = 0.07). Conclusion: Whereas higher total MUFA and n-6 PUFA intakes may be generally beneficial for maintaining cognitive health during aging, a higher consumption of n-3 fatty acids may only be beneficial among individuals with an adequate antioxidant status. These findings underline the importance of not only focusing on specific nutrients for dementia prevention, but also considering the complex interaction between consumed nutrients. This trial was registered at clinicaltrials.gov as NCT00272428.

Fasting and weight-loss restrictive diet practices among 2,700 cancer survivors: results from the NutriNet-Santé cohort.

Nutrition is often used by cancer survivors as a lever to take charge of their own health. However, some dietary behaviors are not currently recommended for patients without medical supervision. Our study aimed at evaluating weight-loss restrictive diets and fasting practices among cancer survivors of the NutriNet-Santé cohort, as well as related socio-demographic and lifestyle factors. In October 2016, 2,741 cancer survivors had completed a specific questionnaire about their practices. Fasting and non-fasting patients (respectively dieting and non-dieting) were compared using logistic regression models. Analyses were weighted according to the age, gender, and cancer location distribution of French cancer cases. 13.8% had already practiced weight-loss restrictive diet as their diagnosis. They were more likely to be women, professionally active, overweight/obese, to use dietary supplements and to have breast cancer (all p < 0.05). 6.0% had already fasted, 3.5% as their diagnosis. They were more likely to be younger, with higher educational level, higher incomes, professionally active, to have a healthy weight, and to use dietary supplements (all p < 0.05). Fasting was associated with the opinion that such practice could improve cancer prognosis (p < 0.0001). Patients who received nutritional information from health care professionals were less likely to practice fasting or weight-loss restrictive diet (0.42[0.27-0.66], p < 0.0001 and 0.49[0.38-0.64], p < 0.0001 respectively). Our study provided original results suggesting that weight-loss restrictive diets are widely practiced by cancer survivors. Fasting was less common in our study though non negligible. Sources of nutritional information received as cancer diagnosis seemed to be a key determinant of these practices.

How Healthy Lifestyle Factors at Midlife Relate to Healthy Aging.

With increasing life expectancies worldwide, it is an important public health issue to identify factors that influence the quality of aging. We aimed to investigate the individual and combined roles of lifestyle factors at midlife for healthy aging (HA). We analyzed data from 2203 participants of the French ”Supplémentation en Vitamines et Minéraux Antioxydants” (SU.VI.MAX) cohort aged 45⁻60 years at baseline (1994⁻1995), and assessed the combined impact of lifestyle factors (weight, smoking status, physical activity, alcohol consumption, and diet) on HA (absence of chronic diseases and function-limiting pain, good physical and cognitive functioning, functional independence, no depressive symptoms, and good social and self-perceived health) with a five-component healthy lifestyle index (HLI). Relative risks (RR) and 95% confidence intervals (CIs) were estimated using a robust-error-variance Poisson regression. Approximately 39% of our sample aged healthily. After adjustment for potential confounders, a one-point increase in HLI was related to an 11% higher probability of HA (95% CI = 6%, 16%; p < 0.001). The proportions of HA attributable to specific factors based on the “population attributable risk” concept were 7.6%, 6.0%, 7.8%, and 16.5% for body mass index (BMI), physical activity, diet quality, and smoking status, respectively. This study highlights the importance of healthy lifestyle habits at midlife for the promotion of good overall health during aging.

MTHFR 677C → T genotype modulates the effect of a 5-year supplementation with B-vitamins on homocysteine concentration: The SU.FOL.OM3 randomized controlled trial.

AIMS: To study how MTHFR 677C→T genotype modulates the effect of supplementation with B-vitamins on total homocysteine (tHcy) and B-vitamin concentrations. METHODS: 2381 patients with a personal history of cardiovascular disease were randomly assigned to one of four groups: 1) B-vitamins alone (560 µg of 5-methyl-THF, 3 mg of vitamin B6 and 20 µg of vitamin B12), 2) n-3 fatty acids alone (600 mg of EPA and DHA in a 2:1 ratio), 3) B-vitamins and n-3 fatty acids, and 4) placebo. Participants were followed up for 4.7 years. At baseline and annually thereafter, biological parameters were assessed. Multivariate and linear mixed models were fit to study the interaction between B-vitamins and MTHFR genotype. RESULTS: Among supplemented participants, concentrations of all three B-vitamins increased during the first year (all p<0.0001) across MTHFR genotype categories. tHcy decreased by 26.3% during the first year (p<0.0001), then steadily increased throughout the 5 years (ptrend<0.001). However, at the end of follow-up, that increase was smaller among TT than among CT or CC subjects (pinteraction<0.02). At baseline, the difference in tHcy concentrations between TT homozygous and CC homozygous subjects was 2.33 µmol/l (p<0.001). After 5 years, that difference was reduced to 1.06 µmol/l and remained statistically significant (p<0.001). CONCLUSION: Participants with the TT genotype exhibited a lower 5-year decrease in tHcy concentrations following a B-vitamin supplementation than did participants with the CC or CT genotype. CLINICAL TRIAL REGISTRATION: Current Controlled Trials # ISRCTN41926726.

The Mediating Role of Overweight and Obesity in the Prospective Association between Overall Dietary Quality and Healthy Aging.

BACKGROUND: Our objective was to quantify to what extent the association between adherence to the French nutritional recommendations at midlife, measured by the Programme National Nutrition Santé-Guideline Score (PNNS-GS), and healthy aging (HA) is mediated by body mass index (BMI) status. METHODS: We analyzed data from 2249 participants of the French 'Supplementation with Vitamins and Mineral Antioxidants' (SU.VI.MAX-'SUpplémentation en VItamines et Minéraux AntioXydants') cohort. At baseline (1994⁻1995), data on BMI status (<25 vs. ≥25 and <30 vs. ≥30) and diet were collected. At follow-up (2007⁻2009), HA status (yes/no) was evaluated via a multidimensional concept focusing on chronic disease incidence, physical and cognitive functioning, mental and social health, pain, and perceived health. Relative risks (RR) were estimated by extensively adjusted robust-error-variance Poisson regression, and counterfactual-based mediation analysis was performed. RESULTS: Our HA criteria were met by 39% of participants. We identified a positive direct relation of a greater adherence to the French nutritional recommendations, with the probability of HA (RRQuartile 4 vsquartile 1 = 1.31 (95% confidence interval (CI) = 1.13, 1.53)), and an indirect relation mediated by BMI status (1.01 (95% CI: 1.01, 1.02)), accounting for 5% of the total relation. CONCLUSION: These results indicate that high dietary quality may contribute to the preservation of overall health during aging, partly via obesity prevention and partly via other mechanisms.

Association Between Alexithymia and Risk of Incident Cardiovascular Diseases in the SUpplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) Cohort.

OBJECTIVE: Although it has been suggested that alexythymia is associated with cardiovascular diseases, studies are scarce and a causal relationship is questionable. This study explored the prospective association between alexithymia and cardiovascular events in middle-aged participants without cardiovascular history at baseline. METHODS: The 26-item Toronto Alexithymia Scale (TAS-26) was completed by 5586 participants of the French SUpplémentation en VItamines et Minéraux AntioXydants cohort (41.4% of men, M [SD] age = 52.2 [6.3] years) in 1996-1997. Covariates measured at baseline included age, occupational status, depressive symptoms, smoking status, body mass index, hypertension, diabetes, hypercholesterolemia, and hypertriglyceridemia. The follow-up ran from January 1, 1998, to the date of the first cardiovascular event, the date of death or September 1, 2007, whichever occurred first. Cardiovascular events were validated by an independent expert committee. Hazard ratios and 95% confidence intervals were computed with Cox regressions. RESULTS: During an average of 8.9 years of follow-up, 171 first cardiovascular events were validated. After adjustment for age, sex, and occupational status, there was no association between baseline alexithymia and cardiovascular events at follow-up (hazard ratio [95% confidence interval] for 15 points of TAS-26 = 1.00 [0.81-1.23], p > .99). Adjusting for all covariates, using binary TAS-26 cut-offs or TAS-26 subscores yielded similar nonsignificant results. CONCLUSIONS: In this large prospective study, alexithymia and cardiovascular events were not associated among a nonclinical population. This casts some doubt on whether alexithymia could be a meaningful target in the prevention of cardiovascular diseases. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov (NCT00272428).

The Inflammatory Potential of the Diet at Midlife Is Associated with Later Healthy Aging in French Adults.

Background: While low-grade chronic inflammation has been suggested as a major modulator of healthy aging (HA), no study has yet investigated the link between the inflammatory potential of the diet and multidimensional concepts of HA. Objective: We aimed to evaluate the association between the inflammatory potential of the diet at midlife, as measured by the Dietary Inflammatory Index (DII), and HA assessed 13 y later. Methods: We analyzed data from 2796 participants in the French Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) study aged 45-60 y at baseline (1994-1995) and initially free of diabetes, cardiovascular disease, and cancer. During the trial phase of the study (1994-2002), participants received either a placebo or a daily nutritional dose of antioxidant supplement (120 mg vitamin C, 6 mg ß-carotene, 30 mg vitamin E, 100 µg Se, 20 mg Zn). HA was assessed in 2007-2009, and defined as having no major chronic disease, good physical and cognitive functioning, independence in daily activities, no depressive symptoms, good social health, good overall self-perceived health, and no function-limiting pain. The DII was calculated based on repeated baseline 24-h dietary records. Its association with HA was assessed by robust-error-variance Poisson regression, providing RR estimates. Results: After adjustment for potential confounders, higher DII scores (reflecting a more proinflammatory diet), were associated with a decreased likelihood of HA: RRtertile 3/tertile 1 = 0.85 (95% CI: 0.74, 0.99); P-trend = 0.03. Secondary analyses revealed that this association was only significant among participants who had been in the placebo group during the trial phase: RRtertile 3/tertile 1 = 0.80 (95% CI: 0.64, 1.00); P-trend = 0.04. Conclusions: This study suggests that a proinflammatory diet may lower the probability of overall HA. The SU.VI.MAX trial was registered at www.clinicaltrials.gov as NCT00272428.

Mindfulness Is Associated with the Metabolic Syndrome among Individuals with a Depressive Symptomatology.

The Metabolic Syndrome (MetS) is a major public health burden. Dispositional mindfulness has recently been associated with eating disorders, being overweight, and could therefore be associated with the MetS. We aimed to examine in a cross-sectional design the relationship between mindfulness, the MetS, and its risk factors in a large sample of the adult general population and the influence of depressive symptomatology on this association. Adults participating in the NutriNet-Santé study who had completed the Five Facets Mindfulness Questionnaire and attended a clinical and biological examination were available for inclusion. Multivariable logistic regression models adjusted for socio-demographic and lifestyle factors were performed. A total of 17,490 individuals were included. Among individuals with a depressive symptomatology, those with higher mindfulness were less likely to have a MetS (OR: 0.73, 95% CI: 0.57-0.93), a high waist circumference, a low HDL-cholesterol level and an elevated fasting blood glucose level (all p <0.05). In those without depressive symptomatology, individuals with higher mindfulness were less likely to have a high waist circumference (p <0.01). In conclusion, higher mindfulness was associated with lower odds of developing a MetS only among individuals with a depressive symptomatology.

Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals.

Importance: Current guidelines advocate the use of marine-derived omega-3 fatty acids supplements for the prevention of coronary heart disease and major vascular events in people with prior coronary heart disease, but large trials of omega-3 fatty acids have produced conflicting results. Objective: To conduct a meta-analysis of all large trials assessing the associations of omega-3 fatty acid supplements with the risk of fatal and nonfatal coronary heart disease and major vascular events in the full study population and prespecified subgroups. Data Sources and Study Selection: This meta-analysis included randomized trials that involved at least 500 participants and a treatment duration of at least 1 year and that assessed associations of omega-3 fatty acids with the risk of vascular events. Data Extraction and Synthesis: Aggregated study-level data were obtained from 10 large randomized clinical trials. Rate ratios for each trial were synthesized using observed minus expected statistics and variances. Summary rate ratios were estimated by a fixed-effects meta-analysis using 95% confidence intervals for major diseases and 99% confidence intervals for all subgroups. Main Outcomes and Measures: The main outcomes included fatal coronary heart disease, nonfatal myocardial infarction, stroke, major vascular events, and all-cause mortality, as well as major vascular events in study population subgroups. Results: Of the 77 917 high-risk individuals participating in the 10 trials, 47 803 (61.4%) were men, and the mean age at entry was 64.0 years; the trials lasted a mean of 4.4 years. The associations of treatment with outcomes were assessed on 6273 coronary heart disease events (2695 coronary heart disease deaths and 2276 nonfatal myocardial infarctions) and 12 001 major vascular events. Randomization to omega-3 fatty acid supplementation (eicosapentaenoic acid dose range, 226-1800 mg/d) had no significant associations with coronary heart disease death (rate ratio [RR], 0.93; 99% CI, 0.83-1.03; P = .05), nonfatal myocardial infarction (RR, 0.97; 99% CI, 0.87-1.08; P = .43) or any coronary heart disease events (RR, 0.96; 95% CI, 0.90-1.01; P = .12). Neither did randomization to omega-3 fatty acid supplementation have any significant associations with major vascular events (RR, 0.97; 95% CI, 0.93-1.01; P = .10), overall or in any subgroups, including subgroups composed of persons with prior coronary heart disease, diabetes, lipid levels greater than a given cutoff level, or statin use. Conclusions and Relevance: This meta-analysis demonstrated that omega-3 fatty acids had no significant association with fatal or nonfatal coronary heart disease or any major vascular events. It provides no support for current recommendations for the use of such supplements in people with a history of coronary heart disease.

NMR metabolomic signatures reveal predictive plasma metabolites associated with long-term risk of developing breast cancer.

Background: Combination of metabolomics and epidemiological approaches opens new perspectives for ground-breaking discoveries. The aim of the present study was to investigate for the first time whether plasma untargeted metabolomic profiles, established from a simple blood draw from healthy women, could contribute to predict the risk of developing breast cancer within the following decade and to better understand the aetiology of this complex disease. Methods: A prospective nested case-control study was set up in the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, including 206 breast cancer cases diagnosed during a 13-year follow-up and 396 matched controls. Untargeted nuclear magnetic resonance (NMR) metabolomic profiles were established from baseline plasma samples. Multivariable conditional logistic regression models were computed for each individual NMR variable and for combinations of variables derived by principal component analysis. Results: Several metabolomic variables from 1D NMR spectroscopy were associated with breast cancer risk. Women characterized by higher fasting plasma levels of valine, lysine, arginine, glutamine, creatine, creatinine and glucose, and lower plasma levels of lipoproteins, lipids, glycoproteins, acetone, glycerol-derived compounds and unsaturated lipids had a higher risk of developing breast cancer. P-values ranged from 0.00007 [odds ratio (OR)T3vsT1=0.37 (0.23-0.61) for glycerol-derived compounds] to 0.04 [ORT3vsT1=1.61 (1.02-2.55) for glutamine]. Conclusion: This study highlighted associations between baseline NMR plasma metabolomic signatures and long-term breast cancer risk. These results provide interesting insights to better understand complex mechanisms involved in breast carcinogenesis and evoke plasma metabolic disorders favourable for carcinogenesis initiation. This study may contribute to develop screening strategies for the identification of at-risk women for breast cancer well before symptoms appear.

Association Between Adherence to the Mediterranean Diet at Midlife and Healthy Aging in a Cohort of French Adults.

Background: The Mediterranean diet has been suggested as a key element for the prevention of age-related chronic diseases. However, very few studies have examined its relation with multidimensional concepts of healthy aging (HA). Our objective was thus to investigate the association between adherence to the Mediterranean diet at midlife and HA. Methods: We analyzed data from 3,012 participants of the French SUpplémentation en Vitamines et Minéraux AntioXydants (SU.VI.MAX) study aged 45-60 years at baseline (1994-1995) and initially free of major chronic diseases, with available data on HA status in 2007-2009. We defined HA as not developing major chronic disease (cancer, cardiovascular disease, or diabetes), good physical and cognitive functioning (evaluated by validated, standardized tests), independence in instrumental activities of daily living, no depressive symptoms, good social functioning, good self-perceived health, and no function-limiting pain. An index assessing adherence to the Mediterranean diet, the Literature-based Adherence Score to the Mediterranean Diet (LAMD) was calculated using baseline data from repeated 24-hour dietary records. Results: In 2007-2009, 38% of participants met the HA criteria. Multivariable logistic regression revealed that higher scores on the LAMD (ORTertile 3 vs Tertile 1: 1.36 [1.12; 1.65]) were associated with higher odds of HA. Supplementary analyses using structural equation modeling revealed a potential mediation of the observed associations by metabolic health-related factors. Conclusions: Our results suggest a favorable role of a high adherence to the Mediterranean diet at midlife for maintaining good overall health during aging.

Prospective association between adherence to the Mediterranean diet and risk of depressive symptoms in the French SU.VI.MAX cohort.

PURPOSE: This study examines whether adherence to the Mediterranean Diet (MD) measured by several dietary indexes was associated with incident depressive symptoms in a large French cohort. METHODS: The study sample consisted of 3523 participants from the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort who had at least three dietary records at baseline during the first 2 years of follow-up (1994-1996), free of depression at the beginning of the study (1996-1997) and available Center for Epidemiologic Studies Depression Scale (CES-D) data at the end of follow-up (2007-2009). The rMED was computed. Incident depressive symptoms were defined by a CES-D score ≥17 for men and ≥23 for women in 2007-2009. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using multivariable logistic regression models. Several sensitivity analyses were performed. RESULTS: In the present study, 172 incident cases of depressive symptoms were identified during the follow-up (mean = 12.6 years). After adjustment for a wide range of potential confounders, adherence to the rMED score (continuous variable) was significantly associated with incident depressive symptoms in men (OR 0.91; 95% CI 0.83-0.99; p = 0.03), but not in women. Use of the Literature-Based Adherence Score to the Mediterranean Diet (LAMD) and the classic MD score (MDS) provide similar findings. CONCLUSIONS: In the current study, higher adherence to the Mediterranean Diet at midlife was associated with a lower risk of incident depressive symptoms, particularly in men, increasing scientific evidence for a beneficial role of Mediterranean Diet on health. Further investigations in particular among women are needed.