Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohort.

BACKGROUND: Emulsifiers are widely used food additives in industrially processed foods to improve texture and enhance shelf-life. Experimental research suggests deleterious effects of emulsifiers on the intestinal microbiota and the metabolome, leading to chronic inflammation and increasing susceptibility to carcinogenesis. However, human epidemiological evidence investigating their association with cancer is nonexistent. This study aimed to assess associations between food additive emulsifiers and cancer risk in a large population-based prospective cohort. METHODS AND FINDINGS: This study included 92,000 adults of the French NutriNet-Santé cohort without prevalent cancer at enrolment (44.5 y [SD: 14.5], 78.8% female, 2009 to 2021). They were followed for an average of 6.7 years [SD: 2.2]. Food additive emulsifier intakes were estimated for participants who provided at least 3 repeated 24-h dietary records linked to comprehensive, brand-specific food composition databases on food additives. Multivariable Cox regressions were conducted to estimate associations between emulsifiers and cancer incidence. Overall, 2,604 incident cancer cases were diagnosed during follow-up (including 750 breast, 322 prostate, and 207 colorectal cancers). Higher intakes of mono- and diglycerides of fatty acids (FAs) (E471) were associated with higher risks of overall cancer (HR high vs. low category = 1.15; 95% CI [1.04, 1.27], p-trend = 0.01), breast cancer (HR = 1.24; 95% CI [1.03, 1.51], p-trend = 0.04), and prostate cancer (HR = 1.46; 95% CI [1.09, 1.97], p-trend = 0.02). In addition, associations with breast cancer risk were observed for higher intakes of total carrageenans (E407 and E407a) (HR = 1.32; 95% CI [1.09, 1.60], p-trend = 0.009) and carrageenan (E407) (HR = 1.28; 95% CI [1.06, 1.56], p-trend = 0.01). No association was detected between any of the emulsifiers and colorectal cancer risk. Several associations with other emulsifiers were observed but were not robust throughout sensitivity analyses. Main limitations include possible exposure measurement errors in emulsifiers intake and potential residual confounding linked to the observational design. CONCLUSIONS: In this large prospective cohort, we observed associations between higher intakes of carrageenans and mono- and diglycerides of fatty acids with overall, breast and prostate cancer risk. These results need replication in other populations. They provide new epidemiological evidence on the role of emulsifiers in cancer risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT03335644.

Dietary exposure to nitrites and nitrates in association with type 2 diabetes risk: Results from the NutriNet-Santé population-based cohort study.

BACKGROUND: Nitrites and nitrates occur naturally in water and soil and are commonly ingested from drinking water and dietary sources. They are also used as food additives, mainly in processed meats, to increase shelf life and to avoid bacterial growth. Experimental studies suggested both benefits and harmful effects of nitrites and nitrates exposure on type 2 diabetes (T2D) onset, but epidemiological and clinical data are lacking. We aimed to study these associations in a large population-based prospective cohort study, distinguishing foods and water-originated nitrites/nitrates from those from food additives. METHODS AND FINDINGS: Overall, 104,168 adults from the French NutriNet-Santé cohort study (2009 to 2021, 79.1% female, mean age [SD] = 42.7 [14.5]) were included. Associations between self-reported exposure to nitrites and nitrates (evaluated using repeated 24-h dietary records, linked to a comprehensive food composition database and accounting for commercial names/brands details of industrial products) and risk of T2D were assessed using cause-specific multivariable Cox proportional hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors). During a median follow-up duration of 7.3 years (interquartile range: [3.2; 10.1] years), 969 incident T2D cases were ascertained. Total nitrites and foods and water-originated nitrites were both positively associated with a higher T2D risk (HRtertile 3 vs.1 = 1.27 (95% CI 1.04 to 1.54), Ptrend = 0.009 and 1.26 (95% CI 1.03 to 1.54), Ptrend = 0.02, respectively). Participants with higher exposure to additives-originated nitrites (i.e., above the sex-specific median) and specifically those having higher exposure to sodium nitrite (e250) had a higher T2D risk compared with those who were not exposed to additives-originated nitrites (HR higher consumers vs. non-consumers = 1.53 (95% CI 1.24 to 1.88), Ptrend < 0.001 and 1.54 (95% CI 1.26 to 1.90), Ptrend < 0.001, respectively). There was no evidence for an association between total, foods and water-originated, or additives-originated nitrates and T2D risk (all Ptrend = 0.7). No causal link can be established from this observational study. Main limitations include possible exposure measurement errors and the lack of validation versus specific nitrites/nitrates biomarkers; potential selection bias linked to the healthier behaviors of the cohort's participants compared to the general population; potential residual confounding linked to the observational design, as well as a self-reported, yet cross-checked, case ascertainment. CONCLUSIONS: The findings of this large prospective cohort did not support any potential benefits for dietary nitrites and nitrates. They suggested that a higher exposure to both foods and water-originated and additives-originated nitrites was associated with higher T2D risk in the NutriNet-Santé cohort. This study provides a new piece of evidence in the context of current debates about updating regulations to limit the use of nitrites as food additives. The results need to be replicated in other populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03335644 (https://clinicaltrials.gov/ct2/show/NCT03335644).

Stages of Change toward Meat Reduction: Associations with Motives and Longitudinal Dietary Data on Animal-Based and Plant-Based Food Intakes in French Adults.

BACKGROUND: Reducing meat consumption is advocated for healthier and more sustainable diets. However, behavioral studies are needed to better understand the mechanisms underlying meat-reducing dietary changes. OBJECTIVES: The main aim of this study was to compare the motives associated with stages of change toward meat reduction in French adults, using the transtheoretical model (TTM). A second aim was to investigate the associations between stages of change and adherence to dietary patterns favoring a better balance of animal and plant food consumption over time. METHODS: This longitudinal study included 25,143 non-vegetarian participants of the web-based NutriNet-Santé cohort with a mean follow-up of 6.2 (SD = 2.6) y. Dietary data were obtained from 24-h dietary records over the period 2009-2019. The contribution of meat to total energy intake and scores measuring the contribution of healthy and unhealthy plant-based foods to the diet were computed. A questionnaire completed in 2018 allowed us to identify the TTM stages of change related to meat reduction (precontemplation, contemplation, preparation, action, and maintenance), and recorded motives related to meat consumption. We used multivariate linear mixed models for repeated data to assess associations between food intake changes and stages, and logistic regression for motives, presented as adjusted frequencies. RESULTS: Participants in later stages were characterized by a significantly higher decrease in meat intake over time, compared with the earliest stage (for example, ßmaintenance ∗ time = -0.08, P < 0.0001), and a higher increase in the healthy plant-based food consumption score over time (for example, ßmaintenance∗time = 0.11, P < 0.0001). Concerns about health, nutrition, and the environment were the most frequently cited motives for reducing meat consumption at all stages. CONCLUSIONS: Individuals who had already initiated meat reduction adhered to healthier and more sustainable diets than meat continuers. Characterizing motives according to readiness to reduce meat consumption could support tailored public health campaigns. TRIAL REGISTRATION NUMBER: The study protocol is registered at clinicaltrials.gov with Clinical Trial Registry number NCT03335644 available at https://clinicaltrials.gov/ct2/show/NCT03335644.

Exposome Profiles and Asthma among French Adults.

Rationale: Although previous studies in environmental epidemiology focused on single or a few exposures, a holistic approach combining multiple preventable risk factors is needed to tackle the etiology of multifactorial diseases such as asthma. Objectives: To investigate the association between combined socioeconomic, external environment, early-life environment, and lifestyle-anthropometric factors and asthma phenotypes. Methods: A total of 20,833 adults from the French NutriNet-Santé cohort were included (mean age, 56.2 yr; SD, 13.2; 72% women). The validated asthma symptom score (continuous) and asthma control (never asthma, controlled asthma, and uncontrolled asthma) were considered. The exposome (n = 87 factors) covered four domains: socioeconomic, external environment, early-life environment, and lifestyle-anthropometric. Cluster-based analyses were performed within each exposome domain, and the identified profiles were studied in association to asthma outcomes in negative binomial (asthma symptom score) or multinomial logistic (asthma control) regression models. Measurements and Main Results: In total, 5,546 (27%) individuals had an asthma symptom score ⩾1, and 1,206 (6%) and 194 (1%) had controlled and uncontrolled asthma, respectively. Three early-life exposure profiles ("high passive smoking-own dogs," "poor birth parameters-daycare attendance-city center," or "⩾2 siblings-breastfed" compared with "farm-pet owner-molds-low passive smoking") and one lifestyle-anthropometric profile ("unhealthy diet-high smoking-overweight" compared with "healthy diet-nonsmoker-thin") were associated with more asthma symptoms and uncontrolled asthma. Conclusions: This large-scale exposome-based study revealed early-life and lifestyle exposure profiles that were at risk for asthma in adults. Our findings support the importance of multiinterventional programs for the primary and secondary prevention of asthma, including control of specific early-life risk factors and promotion of a healthy lifestyle in adulthood.

Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study.

BACKGROUND: The food industry uses artificial sweeteners in a wide range of foods and beverages as alternatives to added sugars, for which deleterious effects on several chronic diseases are now well established. The safety of these food additives is debated, with conflicting findings regarding their role in the aetiology of various diseases. In particular, their carcinogenicity has been suggested by several experimental studies, but robust epidemiological evidence is lacking. Thus, our objective was to investigate the associations between artificial sweetener intakes (total from all dietary sources, and most frequently consumed ones: aspartame [E951], acesulfame-K [E950], and sucralose [E955]) and cancer risk (overall and by site). METHODS AND FINDINGS: Overall, 102,865 adults from the French population-based cohort NutriNet-Santé (2009-2021) were included (median follow-up time = 7.8 years). Dietary intakes and consumption of sweeteners were obtained by repeated 24-hour dietary records including brand names of industrial products. Associations between sweeteners and cancer incidence were assessed by Cox proportional hazards models, adjusted for age, sex, education, physical activity, smoking, body mass index, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, and baseline intakes of energy, alcohol, sodium, saturated fatty acids, fibre, sugar, fruit and vegetables, whole-grain foods, and dairy products. Compared to non-consumers, higher consumers of total artificial sweeteners (i.e., above the median exposure in consumers) had higher risk of overall cancer (n = 3,358 cases, hazard ratio [HR] = 1.13 [95% CI 1.03 to 1.25], P-trend = 0.002). In particular, aspartame (HR = 1.15 [95% CI 1.03 to 1.28], P = 0.002) and acesulfame-K (HR = 1.13 [95% CI 1.01 to 1.26], P = 0.007) were associated with increased cancer risk. Higher risks were also observed for breast cancer (n = 979 cases, HR = 1.22 [95% CI 1.01 to 1.48], P = 0.036, for aspartame) and obesity-related cancers (n = 2,023 cases, HR = 1.13 [95% CI 1.00 to 1.28], P = 0.036, for total artificial sweeteners, and HR = 1.15 [95% CI 1.01 to 1.32], P = 0.026, for aspartame). Limitations of this study include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns. CONCLUSIONS: In this large cohort study, artificial sweeteners (especially aspartame and acesulfame-K), which are used in many food and beverage brands worldwide, were associated with increased cancer risk. These findings provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally. TRIAL REGISTRATION: ClinicalTrials.gov NCT03335644.

Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAPs) and Cancer Risk in the Prospective NutriNet-Santé Cohort.

BACKGROUND: Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) have been shown to be involved in gastrointestinal disorders. In view of their proinflammatory potential and their interactions with the gut microbiota, their contribution to the etiology of other chronic diseases such as cancer has been postulated. However, to our knowledge, no epidemiologic study has investigated this hypothesis so far. OBJECTIVES: Our objective was to investigate the associations between FODMAP intake (total and by type) and cancer risk (overall, breast, prostate, and colorectal) in a large prospective cohort. METHODS: The study was based on the NutriNet-Santé cohort (2009-2020); 104,909 adult participants without cancer at baseline were included in our analyses (median follow-up time = 7.7 y, 78.7% women, mean ± SD age at baseline 42.1 ± 14.5 y). Baseline dietary intakes were obtained from repeated 24-h dietary records linked to a detailed food composition table. Associations between FODMAP intake (expressed in quintiles, Q) and cancer risks were assessed by Cox proportional hazard models adjusted for a large range of lifestyle, sociodemographic, and anthropometric variables. RESULTS: Total FODMAP intake was associated with increased overall cancer risk (n = 3374 incident cases, HR for sex-specific Q5 compared with Q1: 1.21; 95% CI: 1.02, 1.44; P-trend = 0.04). In particular, oligosaccharides were associated with cancer risk: a trend was observed for overall cancer (HR Q5 compared with Q1: 1.10; 95% CI: 0.97, 1.25; P-trend = 0.04) and colorectal cancer (n = 272, HR Q5 compared with Q1: 1.78; 95% CI: 1.13-2.79; P-trend = 0.02). CONCLUSIONS: Results from this large population-based study on French adults from the NutriNet-Santé cohort show a significant association between FODMAP intake and the risk of cancer development. Further epidemiologic and experimental studies are needed to confirm these results and provide data on the potential underlying mechanisms.

Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAPs) and Cancer Risk in the Prospective NutriNet-Santé Cohort.

BACKGROUND: Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) have been shown to be involved in gastrointestinal disorders. In view of their proinflammatory potential and their interactions with the gut microbiota, their contribution to the etiology of other chronic diseases such as cancer has been postulated. However, to our knowledge, no epidemiologic study has investigated this hypothesis so far. OBJECTIVES: Our objective was to investigate the associations between FODMAP intake (total and by type) and cancer risk (overall, breast, prostate, and colorectal) in a large prospective cohort. METHODS: The study was based on the NutriNet-Santé cohort (2009-2020); 104,909 adult participants without cancer at baseline were included in our analyses (median follow-up time = 7.7 y, 78.7% women, mean ± SD age at baseline 42.1 ± 14.5 y). Baseline dietary intakes were obtained from repeated 24-h dietary records linked to a detailed food composition table. Associations between FODMAP intake (expressed in quintiles, Q) and cancer risks were assessed by Cox proportional hazard models adjusted for a large range of lifestyle, sociodemographic, and anthropometric variables. RESULTS: Total FODMAP intake was associated with increased overall cancer risk (n = 3374 incident cases, HR for sex-specific Q5 compared with Q1: 1.21; 95% CI: 1.02, 1.44; P-trend = 0.04). In particular, oligosaccharides were associated with cancer risk: a trend was observed for overall cancer (HR Q5 compared with Q1: 1.10; 95% CI: 0.97, 1.25; P-trend = 0.04) and colorectal cancer (n = 272, HR Q5 compared with Q1: 1.78; 95% CI: 1.13-2.79; P-trend = 0.02). CONCLUSIONS: Results from this large population-based study on French adults from the NutriNet-Santé cohort show a significant association between FODMAP intake and the risk of cancer development. Further epidemiologic and experimental studies are needed to confirm these results and provide data on the potential underlying mechanisms.

Rebalancing meat and legume consumption: change-inducing food choice motives and associated individual characteristics in non-vegetarian adults.

BACKGROUND: A shift toward more plant-based foods in diets is required to improve health and to reduce environmental impact. Little is known about food choice motives and associated characteristics of those individuals who have actually reduced their consumption of animal-based foods. The aim of this cross-sectional study was to identify change-inducing motives related to meat and legume consumptions among non-vegetarians. The association between change-inducing motives and individual characteristics was also studied. METHODS: This study included 25,393 non-vegetarian participants in the French NutriNet-Santé cohort (77.4% women, mean age 55.4 ± 13.9 y.). The motives related to the declared change in meat and legume consumptions (e.g., taste, environment, social pressure) were assessed by an online questionnaire in 2018. For each motive, respondents could be classified into three groups: no motive; motive, not change-inducing; change-inducing motive. Associations between change-inducing motives and individual characteristics were evaluated using multivariable polytomic logistic regressions. Characteristics of participants who rebalanced their meat and legume consumptions were also compared to those who reduced their meat but did not increase their legume consumption. RESULTS: Motives most strongly declared as having induced a change in meat or legume consumptions were health and nutrition (respectively 90.7 and 81.0% declared these motives as change-inducing for the meat reduction), physical environment (82.0% for meat reduction only) and taste preferences (77.7% for legume increase only). Other motives related to social influences, meat avoidance and meat dislike were reported by fewer individuals, but were declared as having induced changes in food consumption. Most motives that induced a meat reduction and a legume increase were more likely to be associated with specific individual characteristics, for example being a woman or highly educated for health motives. CONCLUSIONS: Besides the motives reported as important, some motives less frequently felt important were declared as having induced changes in meat or legume consumptions. Change-inducing motives were reported by specific subpopulations. Public campaigns on health and sustainability could usefully develop new tools to reach populations less willing to change. TRIAL REGISTRATIONS: The study was registered at ClinicalTrials.gov (NCT03335644).

Association between positive psychological traits and changes in dietary behaviour related to first COVID-19 lockdown: A general population-based study.

BACKGROUND: The spread of the coronavirus disease (COVID-19) led many countries to implement lockdown measures, which resulted in changes in dietary behaviours that could persist over the long term and have associated health consequences. Psychological traits may impact these changes given their known association with dietary behaviours. We aimed to investigate in a population-based study, whether positive psychological traits were associated with changes of snacking behaviour and food consumption observed during the first COVID-19 lockdown period. DESIGN: In 2016, levels of optimism, resilience, self-esteem, satisfaction with life, mindfulness and mastery were assessed in 33,766 adults of the French NutriNet-Santé cohort. Snacking and food group consumption were assessed in April-May 2020. Association between psychological traits and changes (no change, increase, decrease) in snacking and food group consumption were assessed using logistic regressions. Multiple correspondence analysis followed by ascending hierarchical classification were used to derive clusters of dietary behaviours. Covariance analyses were used to compare mean scores of psychological traits between clusters. Analyses were adjusted for sociodemographic and lifestyle characteristics, anxiety and depressive symptomatology. RESULTS: Participants with higher levels of optimism, resilience, self-esteem, satisfaction with life, mindfulness or mastery were less likely to change their snacking behaviour and food group consumption of various food groups. Individuals with lower levels were more likely to make changes, with either unhealthy (e.g., less fruits and vegetables, more processed meat) or healthy (e.g., more pasta/rice (whole-grain)) changes. Overall, individuals showed higher levels of positive psychological traits in the "no change" cluster, followed by the "healthy" and the "unhealthy" cluster (all P < 0.05). CONCLUSIONS: Individuals with higher levels of optimism, resilience, self-esteem, satisfaction with life, mindfulness or mastery were less impacted by the lockdown in terms of dietary behaviours.

Nutritional risk factors for SARS-CoV-2 infection: a prospective study within the NutriNet-Santé cohort.

BACKGROUND: Nutritional factors are essential for the functioning of the immune system and could therefore play a role in COVID-19 but evidence is needed. Our objective was to study the associations between diet and the risk of SARS-CoV-2 infection in a large population-based sample. METHODS: Our analyses were conducted in the French prospective NutriNet-Santé cohort study (2009-2020). Seroprevalence of anti-SARS-CoV-2 antibodies was assessed by ELISA on dried blood spots. Dietary intakes were derived from repeated 24 h dietary records (at least 6) in the two years preceding the start of the COVID-19 pandemic in France (February 2020). Multi-adjusted logistic regression models were computed. RESULTS: A total of 7766 adults (70.3% women, mean age: 60.3 years) were included, among which 311 were positive for anti-SARS-CoV-2 antibodies. Dietary intakes of vitamin C (OR for 1 SD=0.86 (0.75-0.98), P=0.02), vitamin B9 (OR=0.84 (0.72-0.98), P=0.02), vitamin K (OR=0.86 (0.74-0.99), P=0.04), fibers (OR=0.84 (0.72-0.98), P=0.02), and fruit and vegetables (OR=0.85 (0.74-0.97), P=0.02) were associated to a decreased probability of SARS-CoV-2 infection while dietary intakes of calcium (OR=1.16 (1.01-1.35), P=0.04) and dairy products (OR=1.19 (1.06-1.33), P=0.002) associated to increased odds. No association was detected with other food groups or nutrients or with the overall diet quality. CONCLUSIONS: Higher dietary intakes of fruit and vegetables and, consistently, of vitamin C, folate, vitamin K and fibers were associated with a lower susceptibility to SARS-CoV-2 infection. Beyond its established role in the prevention of non-communicable diseases, diet could therefore also contribute to prevent some infectious diseases such as COVID-19.

NMR metabolomic profiles associated with long-term risk of prostate cancer.

INTRODUCTION: Prostate cancer is a multifactorial disease whose aetiology is still not fully understood. Metabolomics, by measuring several hundred metabolites simultaneously, could enhance knowledge on the metabolic changes involved and the potential impact of external factors. OBJECTIVES: The aim of the present study was to investigate whether pre-diagnostic plasma metabolomic profiles were associated with the risk of developing a prostate cancer within the following decade. METHODS: A prospective nested case-control study was set up among the 5141 men participant of the SU.VI.MAX cohort, including 171 prostate cancer cases, diagnosed between 1994 and 2007, and 171 matched controls. Nuclear magnetic resonance (NMR) metabolomic profiles were established from baseline plasma samples using NOESY1D and CPMG sequences. Multivariable conditional logistic regression models were computed for each individual NMR signal and for metabolomic patterns derived using principal component analysis. RESULTS: Men with higher fasting plasma levels of valine (odds ratio (OR) = 1.37 [1.07-1.76], p = .01), glutamine (OR = 1.30 [1.00-1.70], p = .047), creatine (OR = 1.37 [1.04-1.80], p = .02), albumin lysyl (OR = 1.48 [1.12-1.95], p = .006 and OR = 1.51 [1.13-2.02], p = .005), tyrosine (OR = 1.40 [1.06-1.85], p = .02), phenylalanine (OR = 1.39 [1.08-1.79], p = .01), histidine (OR = 1.46 [1.12-1.88], p = .004), 3-methylhistidine (OR = 1.37 [1.05-1.80], p = .02) and lower plasma level of urea (OR = .70 [.54-.92], p = .009) had a higher risk of developing a prostate cancer during the 13 years of follow-up. CONCLUSIONS: This exploratory study highlighted associations between baseline plasma metabolomic profiles and long-term risk of developing prostate cancer. If replicated in independent cohort studies, such signatures may improve the identification of men at risk for prostate cancer well before diagnosis and the understanding of this disease.

Depressive symptoms, fruit and vegetables consumption and urinary 3-indoxylsulfate concentration: a nested case-control study in the French Nutrinet-Sante cohort.

PURPOSE: Previous epidemiologic studies have provided some evidence of an inverse association between fruit and vegetables consumption and risk of developing recurrent depressive symptoms. This association could possibly be explained by the role of such dietary factors on the gut microbiota. Especially, indole, a metabolite of tryptophan produced by gut bacteria, may be associated with the development of mood disorders. Thus, the purpose of this study was to investigate relationships between fruit and vegetables intake, recurrent depressive symptoms and indole, using measurement of its main urinary excretion form, i.e., 3-indoxylsulfate, as a biomarker. METHODS: A nested case-control study was conducted in 891 women (aged 45-65) participating to the web-based NutriNet-Santé cohort with available dietary data and biological samples. Cases (individuals with recurrent depressive symptoms, n = 297) were defined as having two Center for Epidemiologic Studies-Depression Scale (CES-D) scores ≥ 16 during the follow-up and were matched with 2 controls having two CES-D scores < 16. Urinary 3-indoxylsulfate concentration was measured as a biomarker of indole production by the gut microbiota. Multivariable conditional logistic regression models were used to test the association of both fruit and vegetables consumption and urine 3-indoxylsulfate measurements with recurrent depressive symptoms. We also tested the association between fruit and vegetables consumption and urinary 3-indoxylsulfate levels using multivariate analysis of variance models. RESULTS: We found a significant inverse association between fruit and vegetables consumption and the risk of having recurrent depressive symptoms over a 2-year period. Fruit and vegetables consumption was inversely associated to urinary 3-indoxylsulfate concentration. However, no significant association was observed between urinary 3-indoxylsulfate levels and recurrent depressive symptoms within this sample. CONCLUSIONS: Our results confirm that low fruit and vegetables consumption could be associated with recurrent depressive symptoms. We also found an inverse association between fruit and vegetable intake and urinary levels of 3-indoxylsulfate. However, it is not possible to conclude to a possible mediation role of the indole produced by the gut microbiota from tryptophan, since there was no relationship between 3-indoxylsulfate and recurrent depressive symptoms.

Prospective association between organic food consumption and the risk of type 2 diabetes: findings from the NutriNet-Santé cohort study.

BACKGROUND: Organic food (OF) consumption has substantially increased in high income countries, mostly driven by environmental concerns and health beliefs. Lower exposure to synthetic pesticides has been systematically documented among consumers of organic products compared to non-consumers. While experimental studies suggest that pesticides currently used in food production may be associated with type 2 diabetes (T2D), no well-conducted prospective studies have investigated the potential association between consumption of organic products and the risk of T2D, controlling for potential confounding factors. The objective of this prospective study was to estimate the association between OF consumption and the risk of T2D. METHODS: A total of 33,256 participants (76% women, mean (SD) age: 53 years (14)) of the French NutriNet-Santé prospective cohort study who completed the organic food frequency questionnaire were included (2014-2019). The proportion of OF in the diet (as weight without drinking water) was computed. The associations between the proportion of OF in the diet (as 5% increment and as quintiles) and the risk of T2D were estimated using multivariable Hazard Ratio (HR) and 95% confidence interval (95% CI) derived from proportional hazards models adjusted for confounders (sociodemographic, anthropometric, lifestyle, medical and nutritional factors). RESULTS: During follow-up (mean = 4.05 y, SD = 1.03 y, 134,990 person-years), 293 incident cases of T2D were identified. After adjustment for confounders including lifestyle (physical activity, smoking status, alcohol consumption) and nutritional quality of the diet assessed by the adherence to the French food-based dietary guidelines, OF consumption was associated with a lower risk of T2D. Participants with the highest quintile of OF consumption, compared with those with the lowest quintile, had 35% lower risk of T2D (95% CI = 0.43-0.97). Each increment of 5% in the proportion of OF in the diet was associated with 3% lower risk of T2D (HR 0.97, 95% CI = 0.95-0.99). CONCLUSIONS: In this large prospective cohort study, OF consumption was inversely associated with the risk of T2D. Further experimental and prospective studies should be conducted to confirm these observations. CLINICAL TRIAL REGISTRY: The study was registered at ClinicalTrials.gov ( NCT03335644 ).

Association between processed meat intake and asthma symptoms in the French NutriNet-Santé cohort.

PURPOSE: Processed meat intake may adversely affect lung health, but data on asthma remains sparse. The magnitude of the processed meat-asthma association may also depend on other unhealthy behaviors. We investigated the association between processed meat intake and the asthma symptom score, and the combined role of unhealthy weight, smoking, low diet quality, and high processed meat intake on the asthma score. METHODS: In 2017, 35,380 participants to the NutriNet-Santé cohort answered a detailed respiratory web-questionnaire. Asthma was defined by the asthma symptom score (sum of 5 questions; continuous variable). Based on repeated 24-h dietary records collected on a dedicated website, processed meat consumption was classified as 0, < 2, 2-5, > 5 servings/week. We examined the combined role of body mass index (BMI) (< 25 vs. ≥ 25 kg/m2), smoking (never vs. ever), diet quality score (highest vs. lowest), and processed meat (≤ 5 vs. > 5 servings/week) on the asthma symptom score. RESULTS: Participants were aged 54 on average (women: 75%, smokers: 49%, BMI ≥ 25: 32%, ≥ 1 asthma symptoms: 27%). After adjustment for confounders, processed meat intake was positively and significantly associated with asthma symptom score: odds ratios (ORs) (95% CI) for > 5 vs. 0 servings/week were 1.15 (1.04-1.27) in women; 1.23 (1.01-1.50) in men. Compared to participants with 0 unhealthy behaviors, ORs for the asthma symptom score among participants with the 4 combined unhealthy behaviors were 2.18 (1.91-2.48) in women; 2.70 (2.10-3.45) in men. CONCLUSION: High processed meat consumption was associated with higher asthma symptoms, and combining overweight/obesity, smoking, low diet quality, with high processed meat intake was strongly associated with asthma symptoms.

Untargeted plasma metabolomic profiles associated with overall diet in women from the SU.VI.MAX cohort.

PURPOSE: Dietary intakes are reflected in plasma by the presence of hundreds of exogenous metabolites and variations in endogenous metabolites. The exploration of diet-related plasma metabolic profiles could help to better understand the impact of overall diet on health. Our aim was to identify metabolomic signatures reflecting overall diet in women from the French general population. METHODS: This cross-sectional study included 160 women in the SU.VI.MAX cohort with detailed dietary data (≥ 10 24-h dietary records) selected according to their level of adherence to the French dietary recommendations, represented by the validated score mPNNS-GS; 80 women from the 10th decile of the score were matched with 80 women from the 1st decile. Plasma metabolomic profiles were acquired using untargeted UPLC-QToF mass spectrometry analysis. The associations between metabolomic profiles and the mPNNG-GS, its components and Principal Component Analyses-derived dietary patterns were investigated using multivariable conditional logistic regression models and partial correlations. RESULTS: Adherence to the dietary recommendations was positively associated with 3-indolepropionic acid and pipecolic acid (also positively associated with fruit and vegetable intake and a healthy diet)-2 metabolites linked to microbiota and inversely associated with lysophosphatidylcholine (LysoPC(17:1)), acylcarnitine C9:1 (also inversely associated with a healthy diet), acylcarnitine C11:1 and 2-deoxy-D-glucose. Increased plasma levels of piperine and Dihydro4mercapto-3(2H) furanone were observed in women who consumed a Western diet and a healthy diet, respectively. Ethyl-ß-D-glucopyranoside was positively associated with alcohol intake. Plasma levels of LysoPC(17:1), cholic acid, phenylalanine-phenylalanine and phenylalanine and carnitine C9:1 decreased with the consumption of vegetable added fat, sweetened food, milk and dairy products and fruit and vegetable intakes, respectively. CONCLUSION: This study highlighted several metabolites from both host and microbial metabolism reflecting the long-term impact of the overall diet. TRIAL REGISTRATION: SU.VI.MAX, clinicaltrials.gov NCT00272428. Registered 3 January 2006, https://clinicaltrials.gov/show/NCT00272428.

Association between dietary fibre intake and asthma (symptoms and control): results from the French national e-cohort NutriNet-Santé.

Despite growing evidence suggesting a potential health benefit of high fibre intake for the prevention of chronic inflammatory diseases, studies regarding the role of total dietary fibre intake, types and sources of fibre on asthma are lacking. The present study aimed to investigate the cross-sectional association of dietary fibre intakes and source of fibre with the asthma symptom score and asthma control. A total of 35 380 participants from the NutriNet-Santé cohort were included. Asthma was defined by the asthma symptom score and asthma control by the asthma control test. Fibre intake (g/d) was categorised according to sex-specific quintiles. Multi-adjusted negative binomial regressions were used to evaluate the association between dietary fibre with the asthma symptom score and logistic regressions with asthma control. Participants were aged on average 54 years. After adjustment for confounders, higher intake of total, soluble, insoluble fibres from cereals, fruit and seeds were significantly negatively associated with the asthma symptom score both among women and men; OR for the highest quintile of total dietary fibre compared with the lowest quintile were 0·73 (95 % CI 0·67, 0·79) in women and 0·63 (95 % CI 0·55, 0·73) in men. We also found inverse significant associations between total, soluble and insoluble fibre with uncontrolled asthma; OR for participants in the highest quintile of total dietary fibre was 0·72 (95 % CI 0·55, 0·95) in women and 0·45 (95 % CI 0·26, 0·79) in men. Our results suggested that higher intake of dietary fibre, mostly insoluble fibre and fibre from cereals, was associated with fewer asthma symptoms and greater asthma control.

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.

Modifications in dietary and alcohol intakes between before and after cancer diagnosis: Results from the prospective population-based NutriNet-Santé cohort.

Postdiagnosis diet and alcohol consumption may be associated with cancer prognosis, recurrence and mortality. Our aim was to investigate food, nutrient and alcohol intake variations between before and after cancer diagnosis and their determinants in a prospective cohort. Subjects (n = 696) were incident cancer cases diagnosed in the NutriNet-Santé cohort between 2009 and 2016. Food, nutrient and alcohol intakes were prospectively collected using repeated nonconsecutive 24-hr dietary records since subjects' inclusion (i.e. an average of 2 y before diagnosis). Mean number of dietary records per subject was 5.9 before and 8.1 after diagnosis. All dietary data before and after diagnosis were compared by mixed models. Factors associated with the main dietary changes observed were also investigated using multivariable logistic regressions. We observed a decrease in intakes of vegetables (mean decrease in intake in patients who decreased their intake=-102.4 ± 79.8 g/d), dairy products (-93.9 ± 82.8 g/d), meat/offal (-35.5 ± 27.8/d), soy products (-85.8 ± 104.1 g/d), sweetened soft drinks (-77.9 ± 95.4 g/d), and alcoholic drinks (-92.9 ± 119.9 g/d), and an increase in broths (42.1 ± 34.9 g/d) and fats/sauces (18.0 ± 13.4 g/d). We observed a decrease in energy intake (-377.2 ± 243.5 kcal/d) and in intakes of alcohol (-7.6 ± 9.4 g/d) proteins (-17.4 ± 12.5 g/d), and several vitamins (p < 0.05) and micronutrients (p < 0.05). Conversely, lipid (19.4 ± 14.6 g/d), SFA (9.3 ± 7.0 g/d), MUFA (8.3 ± 6.3 g/d) and vitamin E (3.9 ± 3.3 mg/d) intakes increased after diagnosis. This large prospective study suggests that cancer diagnosis is a key period for nutritional changes. It highlights some healthy behaviors such as a decrease in alcohol and sweetened drink consumption, but also less favorable trends, such as a decrease in vegetable consumption and in many vitamin and mineral intakes. These results provide insights to identify and target recommendations to put forward for better nutritional care of cancer survivors.

Antioxidant intake from diet and supplements and risk of digestive cancers in middle-aged adults: results from the prospective NutriNet-Santé cohort.

Experimental studies suggest beneficial effects of antioxidants in digestive cancer prevention. However, epidemiological results are contrasting and few studies quantitatively assessed supplemental intake. This study aimed at investigating the associations between antioxidant intakes (dietary, supplemental and total) and digestive cancer risk. This prospective study included 38 812 middle-aged subjects (≥45 years) from the NutriNet-Santé cohort (2009-2016). Dietary data were collected using repeated 24 h records. A specific questionnaire assessed dietary supplement use over a 12-month period. A composition database of about 8000 dietary supplements was developed. Associations between continuous and sex-specific quartiles of vitamins C and E, ß-carotene and Se intakes and digestive cancer risk were characterised using multivariable Cox proportional hazard models. A total of 167 incident digestive cancers (120 colorectal, twenty-six pancreatic, nine oesophagus, seven stomach and five liver) were diagnosed during follow-up investigation. Dietary (hazard ratios (HR)Q4 v. Q1=0·56; 95 % CI 0·34, 0·91, P trend=0·01) and total (HRQ4 v. Q1=0·51; 95 % CI 0·30, 0·84, P trend=0·008) vitamin C intakes, dietary (HRQ4 v. Q1=0·56; 95 % CI 0·34, 0·92, P trend=0·005) and total (HRQ4 v. Q1=0·58; 95 % CI 0·36, 0·94, P trend=0·003) vitamin E intakes, and dietary (HRfor an increment of 10 µg/d=0·92; 95 % CI 0·85, 1·00, P=0·04) and total (HRfor an increment of 10 µg/d=0·92; 95 % CI 0·86, 0·99, P=0·03) Se intakes were associated with a decreased digestive cancer risk. Statistically significant interactions were observed between dietary and total Se intakes and alcohol consumption as well as between total vitamin E intake and smoking status. This prospective cohort study with quantitative assessment of supplemental intakes suggests a potential protective effect of several antioxidants (vitamins C and E and Se) on digestive cancer risk, and a modulation of some of these relationships by alcohol consumption and smoking status.

Sex-specific associations of different anthropometric indices with acute and chronic insomnia.

Background: Sleep disorders, including insomnia, are risk factors for weight gain. However, few epidemiological studies have investigated the association of anthropometric markers with insomnia as an outcome. Methods: In this observational, cross-sectional study, we assessed the association of 3 different anthropometric indices with acute and chronic insomnia. We used data from 13 389 French adults (mean age= 51.9 ± 13.1 years; 70.3% women) enrolled in the NutriNet-Santé-Biobank cohort. Body weight, height, waist and hip circumference were measured once during a clinic visit (2011-14). Body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were the main predictors. Acute (past 8 days) and chronic (≥3 months) insomnia were assessed in 2014 via a self-report questionnaire. We fit multivariable logistic regression models providing odds ratios (OR) and 95% confidence intervals (CI). Results: Overweight (25.0 ≤ BMI < 30.0 kg/m2) and general obesity (BMI ≥ 30.0 kg/m2) appeared to have an inverse association with acute insomnia only among men (overweight: OR= 0.80, 95% CI: 0.70, 0.92; obesity: OR= 0.78, 95% CI: 0.63, 0.98). Obesity assessed by BMI and WHR appeared to be positively associated with chronic insomnia only among women (BMI: OR= 1.23, 95% CI: 1.04, 1.45; WHR: OR= 2.24, 95% CI: 1.07, 4.72). WC did not display any significant associations in either sex. Conclusions: These cross-sectional results revealed sex-specific associations of overweight/obesity with different types of insomnia, and merit confirmation longitudinally with objectively assessed sleep parameters. Nonetheless, the findings reinforce the critical importance of joint health behaviour promotion.