Food additive emulsifiers and the risk of type 2 diabetes: analysis of data from the NutriNet-Santé prospective cohort study.

BACKGROUND: Experimental studies have suggested potential detrimental effects of emulsifiers on gut microbiota, inflammation, and metabolic perturbations. We aimed to investigate the associations between exposures to food additive emulsifiers and the risk of type 2 diabetes in a large prospective cohort of French adults. METHODS: We analysed data from 104 139 adults enrolled in the French NutriNet-Santé prospective cohort study from May 1, 2009, to April 26, 2023; 82 456 (79·2%) were female and the mean age was 42·7 years (SD 14·5). Dietary intakes were assessed with three 24 h dietary records collected over three non-consecutive days, every 6 months. Exposure to additive emulsifiers was evaluated through multiple food composition databases and ad-hoc laboratory assays. Associations between cumulative time-dependent exposures to food additive emulsifiers and the risk of type 2 diabetes were characterised with multivariable proportional hazards Cox models adjusted for known risk factors. The NutriNet-Santé study is registered at ClinicalTrials.gov (NCT03335644). FINDINGS: Of 104 139 participants, 1056 were diagnosed with type 2 diabetes during follow-up (mean follow-up duration 6·8 years [SD 3·7]). Intakes of the following emulsifiers were associated with an increased risk of type 2 diabetes: total carrageenans (hazard ratio [HR] 1·03 [95% CI 1·01-1·05] per increment of 100 mg per day, p<0·0001), carrageenans gum (E407; HR 1·03 [1·01-1·05] per increment of 100 mg per day, p<0·0001), tripotassium phosphate (E340; HR 1·15 [1·02-1·31] per increment of 500 mg per day, p=0·023), acetyl tartaric acid esters of monoglycerides and diglycerides of fatty acids (E472e; HR 1·04 [1·00-1·08] per increment of 100 mg per day, p=0·042), sodium citrate (E331; HR 1·04 [1·01-1·07] per increment of 500 mg per day, p=0·0080), guar gum (E412; HR 1·11 [1·06-1·17] per increment of 500 mg per day, p<0·0001), gum arabic (E414; HR 1·03 [1·01-1·05] per increment of 1000 mg per day, p=0·013), and xanthan gum (E415, HR 1·08 [1·02-1·14] per increment of 500 mg per day, p=0·013). INTERPRETATION: We found direct associations between the risk of type 2 diabetes and exposures to various food additive emulsifiers widely used in industrial foods, in a large prospective cohort of French adults. Further research is needed to prompt re-evaluation of regulations governing the use of additive emulsifiers in the food industry for better consumer protection. FUNDING: European Research Council, French National Cancer Institute, French Ministry of Health, IdEx Université de Paris, and Bettencourt-Schueller Foundation.

Co-occurrence of habit-forming risk behaviors and their socio-demographic, health status and lifestyle determinants: a population-based cross-sectional study.

BACKGROUND: Although habit-forming risk behaviors frequently co-occur, determinants of concurrent risk behaviors have rarely been investigated. The aim of the present study was to investigate socio-demographic, health status, and lifestyle determinants of single versus concurrent risk behaviors in general-population adults. METHODS: We analyzed data from 32,622 participants (74.5% female; mean age = 57.9 ± 14.2 years) of the NutriNet-Santé cohort who completed the Alcohol Use Disorders Identification Test, the 12-item Cigarette Dependence Scale, the modified Yale Food Addiction Scale 2.0, and the Internet Addiction Test in 2021-2022. Using established cutoffs, participants were first split into 2 groups (presence versus absence) for each risk variable (alcohol use disorders, nicotine dependence, food addiction, Internet addiction) and were then divided into 3 groups (no risk behavior, 1 risk behavior (reference), and ≥ 2 risk behaviors). The association between socio-demographic, health status, and lifestyle exposures and individual/concurrent risk behaviors were investigated with polytomous logistic regression. RESULTS: Younger age (Odds Ratio (OR) = 2.04; 95% Confidence Interval (CI: 1.62-2.56), current financial difficulties (OR = 1.29; CI: 1.08-1.54), self-perceived poor health (OR = 1.70; CI: 1.32-2.20), overall poor dietary quality (OR = 2.88; CI: 2.06-4.02), being underweight (OR = 1.46; CI: 1.05-2.04), having obesity (OR = 1.62; CI: 1.31-1.99), lack of affection during childhood (OR = 1.41; CI: 1.18-1.69), and a lifetime prevalence or medication use for a mental disorder (OR = 1.46; CI: 1.24-1.73) were positively associated with having ≥ 2 versus 1 risk behavior (all p < 0.05). The comparison of none versus 1 risk behavior revealed the same determinants in addition to having a higher education, being physically active at work, and being overweight. CONCLUSIONS: We investigated determinants of concurrent habit-forming risk behaviors among adults in a large, population-based study. The findings could serve as impetus for future research in this domain and ultimately help guide addiction prevention efforts.

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.

The association between ultra-processed food consumption and chronic insomnia in the NutriNet-Santé Study.

BACKGROUND: The consumption of ultra-processed foods (UPF) is on the rise worldwide, and it has been linked to numerous health conditions, such as diabetes, obesity, and cancer. Few studies have focused on the effect of UPF consumption on sleep health and even fewer on chronic insomnia. OBJECTIVE: This study investigated the association between UPF intake and chronic insomnia in a large population-based sample. DESIGN: This was a cross-sectional analysis using the NutriNet-Santé study data, an ongoing Web cohort in France. PARTICIPANTS/SETTING: Thirty-eight thousand five hundred seventy adult males and females who had completed a sleep questionnaire (2014) and at least two 24-hour dietary records were included in the analysis. MAIN OUTCOMES MEASURES: Chronic insomnia was defined according to established criteria. Categorization of food and beverages as UPF was based on the NOVA-Group 4 classification. STATISTICAL ANALYSES PERFORMED: The cross-sectional association between UPF intake and chronic insomnia was assessed using multivariable logistic regression. RESULTS: Among the 38,570 participants (mean age, 50.0 ±14.8 years, 77.0% female) included in the analysis, 19.4% had symptoms of chronic insomnia. On average, UPF represented 16% of the total amount (g/day) of the overall dietary intake. In the fully adjusted model, UPF consumption was associated with higher odds of chronic insomnia (odds ratio [OR] for an absolute 10% greater UPF intake in the diet = 1.06; 95% confidence interval [CI]: 1.02-1.09). Sex-specific OR for chronic insomnia for an absolute 10% greater UPF intake in the diet were 1.09 (1.01-1.18) among males and 1.05 (1.01-1.09) among females. CONCLUSIONS: This large epidemiological study revealed a statistically significant association between UPF intake and chronic insomnia, independent of sociodemographic, lifestyle, diet quality, and mental health status covariates. The findings provide insights for future longitudinal research as well as nutrition- and sleep-focused intervention and prevention programs.

Dietary index based on the Food Standards Agency nutrient profiling system and risk of Crohn's disease and ulcerative colitis.

BACKGROUND: Nutri-score is now widely available in food packages in Europe. AIM: To study the overall nutritional quality of the diet in relation to risks of Crohn's disease (CD) and ulcerative colitis (UC), in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort METHODS: We collected dietary data at baseline from validated food frequency questionnaires. We used a dietary index based on the UK Food Standards Agency modified nutrient profiling system (FSAm-NPS-DI) underlying the Nutri-Score label, to measure the nutritional quality of the diet. We estimated the association between FSAm-NPS-DI score, and CD and UC risks using Cox models stratified by centre, sex and age; and adjusted for smoking status, BMI, physical activity, energy intake, educational level and alcohol intake. RESULTS: We included 394,255 participants (68.1% women; mean age at recruitment 52.1 years). After a mean follow-up of 13.6 years, there were 184 incident cases of CD and 459 incident cases of UC. Risk of CD was higher in those with a lower nutritional quality, that is higher FSAm-NPS-DI Score (fourth vs. first quartile: aHR: 2.04, 95% CI: 1.24-3.36; p-trend: <0.01). Among items of the FSAm-NPS-DI Score, low intakes of dietary fibre and fruits/vegetables/legumes/nuts were associated with higher risk of CD. Nutritional quality was not associated with risk of UC (fourth vs. first quartile of the FSAm-NPS-DI Score: aHR: 0.91, 95% CI: 0.69-1.21; p-trend: 0.76). CONCLUSIONS: A diet with low nutritional quality as measured by the FSAm-NPS-DI Score is associated with a higher risk of CD but not UC.

Household Use of Green Cleaning Products, Disinfecting Wipes, and Asthma Control Among Adults.

BACKGROUND: The use of household disinfectants and cleaning products (HDCPs) may negatively impact asthma control, but studies remain scarce. Moreover, no study considered green products or wipes, increasingly used during home cleaning. OBJECTIVE: To assess the associations between the use of HDCPs, including disinfecting wipes and green products, and asthma control based on data from the French Web-based NutriNet-Santé cohort. METHODS: Using a standardized questionnaire (2018), we assessed asthma control (never asthma: reference; controlled: Asthma Control Test ≥ 20; uncontrolled: Asthma Control Test < 20) and the use of HDCPs, including 2 types of products (irritants and green products) and 2 application modes (sprays and disinfecting wipes). Cross-sectional associations of the frequency of weekly use of HDCPs at home with asthma control, adjusted for sex, age, smoking status, body mass index, and educational level were assessed by multinomial logistic regressions. RESULTS: Analyses were performed on 37,043 adults (mean age 47 y; 75% women; 62% with a weekly use of at least 1 HDCP). Strong associations were observed between weekly use of HDCPs and uncontrolled asthma. In particular, an almost daily use (4-7 d/wk) of irritants (odds ratio [OR] 2.81; 95% confidence interval [95% CI] 1.97-4.00) and green products (OR 2.40; 95% CI 1.70-3.39) as well as sprays (OR 2.69; 95% CI 1.97-3.68) and disinfecting wipes (OR 3.51; 95% CI 2.31-5.33) was associated with uncontrolled asthma. When not co-used with irritants and sprays, associations remained statistically significant for both disinfecting wipes and green products. CONCLUSIONS: Weekly use of HDCPs, including green products or wipes, was associated with uncontrolled asthma and should be considered by health practitioners in order to improve asthma control.

Is the number of ideal cardiovascular health metrics in midlife associated with lower risk of cancer? Evidence from 3 European prospective cohorts.

BACKGROUND: Primordial prevention may be a relevant strategy for the prevention of cancer. Given the commonality of risk factors and mechanisms between cancer and cardiovascular disease, we examined the associations between the number of ideal cardiovascular health metrics in midlife and incident cancer. METHODS: In 3 European cohorts (NutriNet-Santé and GAZEL, France; Whitehall II, United Kingdom), the number of ideal cardiovascular health metrics was determined at baseline (range 0-7). Follow-up for cancer events was until October 2020 (NutriNet-Santé), March 2017 (Whitehall II) and December 2015 (GAZEL). Cox regression was conducted in each cohort, and results were thereafter pooled using a random-effects model. RESULTS: Data were available on 39 718 participants. A total of 16 237 were from NutriNet-Santé (mean age 51.3 yr; 28% men), 9418 were from Whitehall II (mean age 44.8 yr; 68% men) and 14 063 were from GAZEL (mean age 45.2 yr; 75% men). The median follow-up was 8.1 years in NutriNet-Santé, 29.6 years in Whitehall II and 24.8 years in GAZEL, and yielded a total of 4889 cancer events. A greater number of ideal cardiovascular health metrics was associated with a lower overall cancer risk in each cohort, with an aggregate hazard ratio (HR) per 1 increment in number of ideal metrics of 0.91 (95% confidence interval [CI] 0.88-0.93). This association remained after removal of the smoking metric (aggregate HR per unit increment in number of ideal metrics: 0.94, 95% CI 0.90-0.97), and site-specific analysis demonstrated a significant association with lung cancer. INTERPRETATION: A greater number of ideal cardiovascular health metrics in midlife was associated with lower cancer risk, notably lung cancer. Primordial prevention of cardiovascular risk factors in midlife may be a complementary strategy to prevent the onset of cancer.

Person-centered and measured life's simple 7 cardiovascular health concordance and association with incident cardiovascular disease.

Person-centered cardiovascular health (CVH) may facilitate cardiovascular disease primordial prevention in low resources settings. The study aims to assess the validity of person-centered CVH compared to gold standard measured CVH by examining the concordance between person-centered vs. measured CVH together with their respective association with incident cardiovascular disease events (CVD). Life's Simple 7 (LS7) CVH metrics, including non-smoking, Body Mass Index, diet, physical activity, blood glycemia, blood pressure, and blood cholesterol were collected from 19,473 adults participating in the e-cohort NutriNet-Santé study from 2011 to 2014 and were followed until September 2020. Clinical examinations and blood analyses defined the measured biological metrics, while diagnoses, medication, or treatment for type 2 diabetes, hypertension, and hypercholesterolemia defined person-centered biological metrics. Declared behavioral metrics were common for both measured and person-centered CVH. The study included 18,714 CVD-free participants (mean age 51 years, 73% women), among whom 16.52% and 38.75% had 5-7 ideal LS7 metrics according to measured and person-centered CVH, respectively. Weighted concordance of person-centered and measured CVH was 0.87 [0.86; 0.88]. Over median follow-up of 8.05 years, 749 CVD events occurred. There was a 7% (HR 0.93 [0.88; 0.99]) and 13% (HR 0.87 [0.83; 0.92]) risk reduction of CVD risk by additional measured and person-centered ideal metrics, respectively. In conclusion, person-centered CVH may represent a reliable alternative to measured CVH.

Urinary Metabolome Analysis Reveals Potential Microbiota Alteration and Electrophilic Burden Induced by High Red Meat Diet: Results from the French NutriNet-Santé Cohort and an In Vivo Intervention Study in Rats.

SCOPE: High red and processed meat consumption is associated with several adverse outcomes such as colorectal cancer and overall global mortality. However, the underlying mechanisms remain debated and need to be elucidated. METHODS AND RESULTS: Urinary untargeted Liquid Chromatography-Mass Spectrometry (LC-MS) metabolomics data from 240 subjects from the French cohort NutriNet-Santé are analyzed. Individuals are matched and divided into three groups according to their consumption of red and processed meat: high red and processed meat consumers, non-red and processed meat consumers, and at random group. Results are supported by a preclinical experiment where rats are fed either a high red meat or a control diet. Microbiota derived metabolites, in particular indoxyl sulfate and cinnamoylglycine, are found impacted by the high red meat diet in both studies, suggesting a modification of microbiota by the high red/processed meat diet. Rat microbiota sequencing analysis strengthens this observation. Although not evidenced in the human study, rat mercapturic acid profile concomitantly reveals an increased lipid peroxidation induced by high red meat diet. CONCLUSION: Novel microbiota metabolites are identified as red meat consumption potential biomarkers, suggesting a deleterious effect, which could partly explain the adverse effects associated with high red and processed meat consumption.

The ability of five different front-of-pack labels to assist Australian consumers to identify healthy versus unhealthy foods.

OBJECTIVE: The aim of this study was to assess the relative ability of different interpretive front-of-pack food labels to alert consumers to both healthier and unhealthier options to inform their food choices. METHODS: One thousand Australians completed an online experiment where they rated the nutritional quality of sets of fictional products pre- and post-randomisation to one of five front-of-pack labels: Health Star Rating, Multiple Traffic Lights, Nutri-Score, Reference Intakes and Warning Label. Two sample z-tests were used to assess the ability of each label to facilitate the correct identification of the least and most healthy product options. RESULTS: The Nutri-Score was superior in assisting respondents to identify both the healthiest and unhealthiest options. The Health Star Rating ranked second for both outcomes, followed by the Multiple Traffic Lights. CONCLUSIONS: Results reinforce the role of interpretive front-of-pack labels in assisting consumers to understand the nutritional quality of food products and suggest spectrum labels may provide superior utility in assisting consumers to identify both the most and least nutritious products from among available product options. IMPLICATIONS FOR PUBLIC HEALTH: The strongest performance of a highly interpretive front-of-pack label (Nutri-Score) featuring colour in a summary indicator suggests potential strategies for enhancing the performance of the Health Star Rating.

Periodontitis assessed with a new screening tool and oral health-related quality of life: cross-sectional findings among general-population adults.

INTRODUCTION: Periodontitis, as a chronic, multifactorial inflammatory disease, has complex relationships with other diseases and ultimately with well-being. The aim of this cross-sectional study was to investigate the association between self-report periodontitis, as measured with the recently developed and validated modified Periodontal Screening Score (mPESS), and oral health-related quality of life (OHRQol) in a large population-based sample derived from the French NutriNet-Santé e-cohort. METHODS: The sample was composed of 32,714 adults (75.5% women) with a mean age of 48.8 ± 13.9 years. Periodontitis was assessed based on age, smoking, and oral health status data obtained in 2011-2012, which allowed calculating the mPESS. An mPESS ≥ 5 was used to identify individuals at risk of severe periodontitis (main exposure). OHRQoL was measured with the Oral Health Impact Profile (OHIP-14) (main outcome) and the total score was dichotomized for analysis. Multivariable logistic regression analyses, considering physical health status, dietary and lifestyle confounding variables, were performed. RESULTS: Overall, 6407 participants (19.6%) were at a high risk of severe periodontitis. A total of 7383 participants (22.6%) presented a relatively poor OHRQoL (OHIP-14 > 8, highest quartile). In the multivariable model, each of the following variables was independently and significantly associated with lower OHRQoL: older age (50-64 years), female sex, obesity, snacking between meals, frequent consumption of soft drinks and sweets/chocolate, risk of severe periodontitis, and having < 20 natural teeth were significantly. An mPESS ≥ 5 showed the highest odds for relatively poor OHRQoL (OR = 3.45; 95% CI 3.21-3.72). CONCLUSION: The results support the association between periodontitis and OHRQoL in non-clinical samples. The use of mPESS could be tested in future prevention programs aiming at improving OHRQoL.

Behavioural risk patterns in adolescents with excess weight participating in the PRALIMAP-INÈS trial.

OBJECTIVE: To investigate clustering of risk behaviours in adolescents with excess weight. DESIGN: Cross-sectional analysis of baseline data from the PRALIMAP-INÈS trial. Information on food frequency consumption (fruit, vegetables, sugary products and beverages), physical activity, sedentary behaviour (week and weekend days), smoking and alcohol consumption (current frequency and intoxication episodes) and socio-demographic data was collected using self-reported questionnaires. Behavioural risk factors were entered as categorical variables in a two-step clustering procedure: multiple correspondence analysis followed by hierarchical clustering. Associations between cluster membership and socio-demographic variables were investigated using multivariable multinomial logistic regression. SETTING: French PRALIMAP-INÈS trial. PARTICIPANTS: Adolescents with excess weight. RESULTS: A total of 1391 participants (13-18 years old, 58·2 % female) were included in the analysis, which resulted in the identification of four groups of participants, including, respectively, 543 (39·0 %), 373 (26·8 %), 246 (17·7 %) and 229 (16·5 %) participants. Clusters 1 and 4 showed associations of rather healthy behaviours (high physical activity and low consumption of sugary products; high consumption of fruit and vegetables, respectively), while clusters 2 and 3 showed associations of rather unhealthy behaviours (high sedentary behaviour and low consumption of fruit and vegetables; smoking and alcohol consumption, respectively). Both social status and family structure were associated with cluster membership. CONCLUSIONS: Risk behaviour patterns in adolescents with excess weight were clustered in both healthier and less healthy ways, with a complex interplay with socio-demographic factors.

Occupational Exposures to Irritants and Sensitizers, Asthma and Asthma Control in the Nutrinet-Santé Cohort.

BACKGROUND: The role of chronic occupational exposures to irritants in asthma remains not well-defined. Few studies have examined their associations with asthma and its control. OBJECTIVE: To study the associations of occupational exposures with asthma and its control, with specific interest for irritants, including disinfectants and cleaning products (DCPs) and solvents. METHODS: Analyses included 4,469 adults (3,792 with neither asthma nor respiratory symptoms, 677 with current asthma; 75.9% women, mean age 54 years) of a case-control study (2018) from the French NutriNet-Santé cohort. Current asthma was defined by ever asthma with symptoms, medication or asthma attacks in the past 12 months, adult-onset asthma by age at first asthma attack older than 16 years, and uncontrolled asthma was defined by an Asthma Control Test score less than 20. Ever/current exposures were assessed with the Occupational Asthma-specific Job Exposure Matrix. Associations were evaluated by multinomial logistic regressions adjusted for sex, age, smoking status, and body mass index. RESULTS: Ever exposures to sensitizers (high molecular weight [HMW]: OR 1.53, 95% CI 1.18-2.00; and low molecular weight [LMW]: OR 1.42; 95% CI 1.09-1.87), irritants (OR 1.32; 95% CI 1.03-1.68), and DCPs (OR 1.43; 95% CI 1.10-1.85) were associated with current adult-onset asthma. Significant associations between ever exposures and uncontrolled adult-onset asthma were observed for high molecular weight (OR 2.69; 95% CI 1.52-4.78) and low molecular weight (OR 2.27; 95% CI 1.24-4.37) sensitizers, irritants (OR 2.32; 95% CI 1.36-3.95), and DCPs (OR 2.59; 95% CI 1.48-4.54). Results were similar for current exposures, with higher ORs. No association was observed with solvents. CONCLUSIONS: Occupational exposures to both sensitizers and irritants were associated with current adult-onset asthma and uncontrolled asthma. Irritant and sensitizing agents should be carefully considered in asthma management.

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.

Association between adherence to the EAT-Lancet diet and risk of cancer and cardiovascular outcomes in the prospective NutriNet-Santé cohort.

BACKGROUND: The EAT-Lancet commission proposed, in 2019, a planetary, healthy, and universal dietary pattern. However, this diet has rarely been studied in relation to various health outcomes. OBJECTIVES: We aimed to prospectively estimate the association between the EAT-Lancet diet and cancer and cardiovascular disease (CVD) risk. METHODS: The study was conducted in participants of the NutriNet-Santé cohort (2009-2021). The endpoints were the incident outcomes (cancer and CVDs and mortality from these diseases), combined and separately. Adherence to the EAT-Lancet diet was estimated using the EAT-Lancet Diet Index (ELD-I) modeled as quintiles (Qs). Multivariable Cox proportional hazard models were used to estimate HRs and 95% CIs, adjusted for potential confounders and moderators. RESULTS: A total of 62,382 subjects were included; 2475 cases of cancer and 786 cases of cardiovascular events occurred during a median follow-up of 8.1 y. The sample was 76% female, the mean ± SD age at inclusion was 51.0 ± 10.2 y. The ELD-I ranged from -162 to 332 points with a mean ± SD score of 45.4 ± 25.6 points. In multivariable models, no significant association between the EAT-Lancet diet and the risk of cancer and CVD combined, and separately, was observed. Alcohol consumption was an effect modifier of the association. A significant association was observed among low drinkers (HRQ5vs.Q1: 0.86; 95% CI: 0.73, 1.02; P-trend = 0.02). A higher ELD-I was significantly associated with a lower risk of overall cancer only among females (HRQ5vs.Q1: 0.89; 95% CI: 0.75, 1.05; P-trend = 0.03). Both associations were largely attenuated by BMI. CONCLUSIONS: Contrary to our hypothesis, our results documented significant associations between adherence to the EAT-Lancet diet and incidence of cancer only in some subgroups, and no association with CVD.This trial was registered at clinicaltrials.gov as 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.

Nitrites and nitrates from food additives and natural sources and cancer risk: results from the NutriNet-Santé cohort.

BACKGROUND: Nitrates and nitrites occur naturally in water and soil. They are also used as food additives (preservatives) in processed meats. They could play a role in the carcinogenicity of processed meat. The objective was to investigate the relationship between nitrate and nitrite intakes (natural food, water and food additive sources) and cancer risk in a large prospective cohort with detailed dietary assessment. METHODS: Overall, 101    056 adults from the French NutriNet-Santé cohort (2009-ongoing, median follow-up 6.7 years) were included. Nitrites/nitrates exposure was evaluated using repeated 24-h dietary records, linked to a comprehensive composition database and accounting for commercial names/brands of industrial products. Associations with cancer risk were assessed using multi-adjusted Cox hazard models. RESULTS: In total, 3311 incident cancer cases were diagnosed. Compared with non-consumers, high consumers of food additive nitrates had higher breast cancer risk [hazard ratio (HR) = 1.24 (95% CI 1.03-1.48), P = 0.02], more specifically for potassium nitrate. High consumers of food additive nitrites had higher prostate cancer risk [HR = 1.58 (1.14-2.18), P = 0.008], specifically for sodium nitrite. Although similar HRs were observed for colorectal cancer for additive nitrites [HR = 1.22 (0.85-1.75)] and nitrates [HR = 1.26 (0.90-1.76)], no association was detected, maybe due to limited statistical power for this cancer location. No association was observed for natural sources. CONCLUSION: Food additive nitrates and nitrites were positively associated with breast and prostate cancer risks, respectively. Although these results need confirmation in other large-scale prospective studies, they provide new insights in a context of lively debate around the ban of these additives from the food industry.

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.