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.

Adherence to the ultra-processed dietary pattern and risk of depressive outcomes: Findings from the NutriNet Brasil cohort study and an updated systematic review and meta-analysis.

BACKGROUND & AIMS: We aimed to analyze the prospective association between adherence to the ultra-processed dietary pattern and risk of depressive outcomes using original data from the NutriNet Brasil cohort and via a systematic review and meta-analysis of observational studies that have investigated the same association. METHODS: In our original research analysis, we used data from 15,960 adults (≥18 y) participating in the NutriNet Brasil cohort study, free of depression or depressive symptoms during the baseline (77.5% women, 45.8 ± 13.0 y). The mean dietary share of ultra-processed foods (%Kcal/d), calculated from two baseline 24-h dietary recalls, was used to measure the adherence to the ultra-processed dietary pattern. New cases of depressive symptoms were assessed using the Patient Health Questionnaire-9 over the follow-up period (mean: 18.3 months). Cox proportional hazards models were used for the main analyses. In our systematic review and meta-analysis, we incorporated effect estimates from six prospective cohort studies that have examined the same association, including ours. RESULTS: In the adjusted model, each 10% increase in the dietary share of ultra-processed foods was associated with a 10% increase in the hazard of incident cases of depressive symptoms (HR:1.10; 95%CI: 1.07-1.14). This association was slightly attenuated in the models including potential mediators. In our meta-analysis of six prospective studies, high versus low exposure to ultra-processed foods was associated with a summary hazard ratio of depressive outcomes of 1.32; 95%CI: 1.19-1.46; I2: 71%. CONCLUSION: A higher adherence to the ultra-processed dietary pattern was associated with a higher risk of developing depressive outcomes in the NutriNet Brasil cohort and in the meta-analysis.

How far can reformulation participate in improving the nutritional quality of diets at population level? A modelling study using real food market data in France.

BACKGROUND: Food reformulation is promoted as a tool to improve the nutritional quality of population diets. However, the potential impact of industry-wide reformulation on dietary intake has been investigated minimally. OBJECTIVES: The aim was to estimate the impact on the French population nutrient intakes of industry-wide reformulation towards healthier products using the updated nutrient profiling system underpinning the front-of-pack nutrition label Nutri-Score (uNS-NPS). METHODS: Dietary data were retrieved from the Nutrinet-Santé cohort at baseline (N=100 418), providing detailed information regarding participants' food choices (N>3000 generic food items). Each individual food from 24 hours dietary record was matched with French food market data from OpenFoodFacts database (N=119 073 products). Three scenarios were constructed using nutrient content of currently existing food products: (1) all products available (baseline situation); (2) only existing products of better nutritional quality were available as potential substitutes and (3) only existing products of poorer quality were available. The assessment of the nutritional quality was based on the uNS-NPS score. Finally, dietary intakes were calculated for each scenario after random attribution of healthier/less healthy products as dietary choices. Monte-Carlo iterations (n=300) were conducted to generate uncertainty intervals. RESULTS: After simulation of reformulation using scenario 2, reduction in daily intake in comparison with the baseline situation was observed for energy (-55 kcal/day, -2.9%), saturated fat (-2.4g/day, -7.6%), sugar (-4.8g/day, -5.3%) and salt (-0.54g/day, -8.3%) and increase was observed for fibre (+1.0g/day, +4.9%). Improvements in diet quality were observed regardless of the overall quality of diet. The most important contributors to diet improvement were the followings: (1) sugars: sugary products, sweet bakery products and dairy products; (2) saturated fat: sweet bakery products, dairy products and prepared dishes and (3) salt: bread, prepared dishes, vegetable preparations and soups. CONCLUSION: Widespread reformulation of food offer appeared to be an opportunity for improving nutritional status at population level in France.

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.

Ultra-processed food exposure and adverse health outcomes: umbrella review of epidemiological meta-analyses.

OBJECTIVE: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. DESIGN: Systematic umbrella review of existing meta-analyses. DATA SOURCES: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manual searches of reference lists from 2009 to June 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews and meta-analyses of cohort, case-control, and/or cross sectional study designs. To evaluate the credibility of evidence, pre-specified evidence classification criteria were applied, graded as convincing ("class I"), highly suggestive ("class II"), suggestive ("class III"), weak ("class IV"), or no evidence ("class V"). The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework, categorised as "high," "moderate," "low," or "very low" quality. RESULTS: The search identified 45 unique pooled analyses, including 13 dose-response associations and 32 non-dose-response associations (n=9 888 373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health parameters spanning mortality, cancer, and mental, respiratory, cardiovascular, gastrointestinal, and metabolic health outcomes. Based on the pre-specified evidence classification criteria, convincing evidence (class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease related mortality (risk ratio 1.50, 95% confidence interval 1.37 to 1.63; GRADE=very low) and type 2 diabetes (dose-response risk ratio 1.12, 1.11 to 1.13; moderate), as well as higher risks of prevalent anxiety outcomes (odds ratio 1.48, 1.37 to 1.59; low) and combined common mental disorder outcomes (odds ratio 1.53, 1.43 to 1.63; low). Highly suggestive (class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all cause mortality (risk ratio 1.21, 1.15 to 1.27; low), heart disease related mortality (hazard ratio 1.66, 1.51 to 1.84; low), type 2 diabetes (odds ratio 1.40, 1.23 to 1.59; very low), and depressive outcomes (hazard ratio 1.22, 1.16 to 1.28; low), together with higher risks of prevalent adverse sleep related outcomes (odds ratio 1.41, 1.24 to 1.61; low), wheezing (risk ratio 1.40, 1.27 to 1.55; low), and obesity (odds ratio 1.55, 1.36 to 1.77; low). Of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (class III-IV) and 13 were graded as no evidence (class V). Overall, using the GRADE framework, 22 pooled analyses were rated as low quality, with 19 rated as very low quality and four rated as moderate quality. CONCLUSIONS: Greater exposure to ultra-processed food was associated with a higher risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to develop and evaluate the effectiveness of using population based and public health measures to target and reduce dietary exposure to ultra-processed foods for improved human health. They also inform and provide support for urgent mechanistic research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023412732.

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.

Consistency of the Initial and Updated Version of the Nutri-Score with Food-Based Dietary Guidelines: A French Perspective.

BACKGROUND: To help consumers to make healthier food choices, 7 European countries have implemented the front-of-pack nutrition label Nutri-Score. The algorithm was updated in 2022-2023 by the Nutri-Score European scientific committee, based on the current scientific knowledge. OBJECTIVES: The aim of this study was to investigate the consistency of the newly internationally developed algorithm with the French food-based dietary guidelines (FBDG) and compare the respective performances of the initial and updated algorithm. METHODS: Three complementary French food composition databases were used to access extensive coverage of the food supply in France (n = 46,752): the Oqali, OpenFoodFacts, and CIQUAL databases. Based on the French FBDG, a list of 41 criteria was defined by which the consistency between French FBDG and the Nutri-Score was assessed (eg, consumption of fresh vegetables is promoted in FBDG, thus the Nutri-Score should rate favorably such products). RESULTS: Of all criteria, the initial algorithm met 63% (26/41) of them, whereas the revised algorithm met 85% (35/41) of them. Improvements achieved by the updated version of the Nutri-Score in alignment with the FBDG were particularly observed for high-fat products (ie, fatty fish, nuts, and seeds), sweet products (ie, ice creams and sweet spreads), salty products (ie, savory snacks and salted nuts), dairy beverages, and beverages with artificial sweeteners. CONCLUSIONS: The Nutri-Score's updated nutrient profiling system appears to rate foods more consistently regarding the French dietary guidelines and improved the currently existing system. This work supports the implementation of the updated nutrient profiling system underlying Nutri-Score.

Complementarity between the updated version of the front-of-pack nutrition label Nutri-Score and the food-processing NOVA classification.

OBJECTIVE: To compare the initial and the updated versions of the front-of-pack label Nutri-Score (related to the nutritional content) with the NOVA classification (related to the degree of food processing) at the food level. DESIGN: Using the OpenFoodFacts database - 129,950 food products - we assessed the complementarity between the Nutri-Score (initial and updated) with the NOVA classification through a correspondence analysis. Contingency tables between the two classification systems were used. SETTINGS: The food offer in France. PARTICIPANTS: Not applicable. RESULTS: With both versions (i.e. initial and updated) of the Nutri-Score, the majority of ultra-processed products received medium to poor Nutri-Score ratings (between 77·9 % and 87·5 % of ultra-processed products depending on the version of the algorithm). Overall, the update of the Nutri-Score algorithm led to a reduction in the number of products rated A and B and an increase in the number of products rated D or E for all NOVA categories, with unprocessed foods being the least impacted (-3·8 percentage points (-5·2 %) rated A or B and +1·3 percentage points (+12·9 %) rated D or E) and ultra-processed foods the most impacted (-9·8 percentage points (-43·4 %) rated A or B and +7·8 percentage points (+14·1 %) rated D or E). Among ultra-processed foods rated favourably with the initial Nutri-Score, artificially sweetened beverages, sweetened plant-based drinks and bread products were the most penalised categories by the revision of Nutri-Score while low-sugar flavoured waters, fruit and legume preparations were the least affected. CONCLUSION: These results indicate that the update of the Nutri-Score reinforces its coherence with the NOVA classification, even though both systems measure two distinct health dimensions at the food level.

Dietary circadian rhythms and cardiovascular disease risk in the prospective NutriNet-Santé cohort.

Daily eating/fasting cycles synchronise circadian peripheral clocks, involved in the regulation of the cardiovascular system. However, the associations of daily meal and fasting timing with cardiovascular disease (CVD) incidence remain unclear. We used data from 103,389 adults in the NutriNet-Santé study. Meal timing and number of eating occasions were estimated from repeated 24 h dietary records. We built multivariable Cox proportional-hazards models to examine their association with the risk of CVD, coronary heart disease and cerebrovascular disease. In this study, having a later first meal (later than 9AM compared to earlier than 8AM) and last meal of the day (later than 9PM compared to earlier than 8PM) was associated with a higher risk of cardiovascular outcomes, especially among women. Our results suggest a potential benefit of adopting earlier eating timing patterns, and coupling a longer nighttime fasting period with an early last meal, rather than breakfast skipping, in CVD prevention.

Association of SARS-CoV-2 infection with physical activity domains and types.

Lockdown imposed in the early phase of the SARS-CoV-2 outbreak represented a specific setting where activity was restricted but still possible. The aim was to investigate the cross-sectional associations between physical activity (PA) and SARS-CoV-2 infection in a French population-based cohort. Participants completed a PA questionnaire. PA was classified into: (i) total PA; (ii) aerobic PA by intensity; (iii) strengthening PA; (iv) PA by domain and type; and (vii) by location. Sedentary time was also recorded. Seroprevalence of anti-SARS-CoV-2 antibodies was assessed. Multivariable logistic regression models controlling for sociodemographic, lifestyle, anthropometric data, health status, and adherence to recommended protective anti-SARS-CoV-2 behaviours were computed. From 22,165 participants included, 21,074 (95.1%) and 1091 (4.9%) had a negative and positive ELISA-S test result, respectively. Total PA, vigorous PA, leisure-time PA, household PA, outdoor PA and indoor PA were all associated with lower probability of SARS-CoV-2 infection. Observations made in such a setting shed light on PA possibilities in a context of restricted mobility, where the health benefits of PA should not be overlooked. Along with already well-established benefits of PA for non-communicable disease prevention, these findings provide additional evidence for policies promoting all types of PA as a lever for population health.

Food additive emulsifiers and risk of cardiovascular disease in the NutriNet-Santé cohort: prospective cohort study.

OBJECTIVE: To assess the associations between exposure to food additive emulsifiers and risk of cardiovascular disease (CVD). DESIGN: Prospective cohort study. SETTING: French NutriNet-Santé study, 2009-21. PARTICIPANTS: 95 442 adults (>18 years) without prevalent CVD who completed at least three 24 hour dietary records during the first two years of follow-up. MAIN OUTCOME MEASURES: Associations between intake of food additive emulsifiers (continuous (mg/day)) and risk of CVD, coronary heart disease, and cerebrovascular disease characterised using multivariable proportional hazard Cox models to compute hazard ratios for each additional standard deviation (SD) of emulsifier intake, along with 95% confidence intervals. RESULTS: Mean age was 43.1 (SD 14.5) years, and 79.0% (n=75 390) of participants were women. During follow-up (median 7.4 years), 1995 incident CVD, 1044 coronary heart disease, and 974 cerebrovascular disease events were diagnosed. Higher intake of celluloses (E460-E468) was found to be positively associated with higher risks of CVD (hazard ratio for an increase of 1 standard deviation 1.05, 95% confidence interval 1.02 to 1.09, P=0.003) and coronary heart disease (1.07, 1.02 to 1.12, P=0.004). Specifically, higher cellulose E460 intake was linked to higher risks of CVD (1.05, 1.01 to 1.09, P=0.007) and coronary heart disease (1.07, 1.02 to 1.12, P=0.005), and higher intake of carboxymethylcellulose (E466) was associated with higher risks of CVD (1.03, 1.01 to 1.05, P=0.004) and coronary heart disease (1.04, 1.02 to 1.06, P=0.001). Additionally, higher intakes of monoglycerides and diglycerides of fatty acids (E471 and E472) were associated with higher risks of all outcomes. Among these emulsifiers, lactic ester of monoglycerides and diglycerides of fatty acids (E472b) was associated with higher risks of CVD (1.06, 1.02 to 1.10, P=0.002) and cerebrovascular disease (1.11, 1.06 to 1.16, P<0.001), and citric acid ester of monoglycerides and diglycerides of fatty acids (E472c) was associated with higher risks of CVD (1.04, 1.02 to 1.07, P=0.004) and coronary heart disease (1.06, 1.03 to 1.09, P<0.001). High intake of trisodium phosphate (E339) was associated with an increased risk of coronary heart disease (1.06, 1.00 to 1.12, P=0.03). Sensitivity analyses showed consistent associations. CONCLUSION: This study found positive associations between risk of CVD and intake of five individual and two groups of food additive emulsifiers widely used in industrial foods. TRIAL REGISTRATION: ClinicalTrials.gov NCT03335644.

Nova diet quality scores and risk of weight gain in the NutriNet-Brasil cohort study.

OBJECTIVE: To assess the prospective association of two diet quality scores based on the Nova food classification with BMI gain. DESIGN: The NutriNet-Brasil cohort is an ongoing web-based prospective study with continuous recruitment of participants aged ≥ 18 years since January 2020. A short 24-h dietary recall screener including 'yes/no' questions about the consumption of whole plant foods (WPF) and ultra-processed foods (UPF) was completed by participants at baseline. The Nova-WPF and the Nova-UPF scores were computed by adding up positive responses regarding the consumption of thirty-three varieties of WPF and twenty-three varieties of UPF, respectively. Participants reported their height at baseline and their weight at both baseline and after approximately 15 months of follow-up. A 15-month BMI (kg/m2) increase of ≥5 % was coded as BMI gain. SETTING: Brazil. PARTICIPANTS: 9551 participants from the NutriNet-Brasil cohort. RESULTS: Increasing quintiles of the Nova-UPF score were linearly associated with higher risk of BMI gain (relative risk Q5/Q1 = 1·34; 95 % CI 1·15, 1·56), whereas increasing quintiles of the Nova-WPF score were linearly associated with lower risk (relative risk Q5/Q1 = 0·80; 95 % CI 0·69, 0·94). We identified a moderate inverse correlation between the two scores (-0·33) and a partial mediating effect of the alternative score: 15 % for the total effect of the Nova-UPF score and 25 % for the total effect of the Nova-WPF score. CONCLUSIONS: The Nova-UPF and Nova-WPF scores are independently associated with mid-term BMI gain further justifying their use in diet quality monitoring systems.

Effect of a new graphically modified Nutri-Score on the objective understanding of foods' nutrient profile and ultraprocessing: a randomised controlled trial.

Introduction: When considering health-related impacts of foods, nutrient profile and (ultra)processing are two complementary dimensions. The Nutri-Score informs on the nutrient profile dimension. Recently, mounting evidence linked ultraprocessed food consumption to various adverse health outcomes, independently of their nutrient profile. To inform consumers about each of these health-related dimensions of food, we tested, in a randomised controlled trial, if a graphically modified version 'Nutri-Score V.2.0', including a black 'ultraprocessed' banner, would improve the capacity of consumers to rank products according to their nutrient profile and to detect those ultra-processed, compared with a no-label situation. Methods: 21 159 participants included in the NutriNet-Santé web-cohort were randomly assigned to a control arm (no front-of-pack label) or an experimental arm (Nutri-Score 2.0) and were presented an online questionnaire with three sets of food products (cookies, breakfast cereals and ready-to-eat meals) to rank according to nutrient profile and to identify ultraprocessed foods. The primary outcome was objective understanding of nutrient profile and ultraprocessing, represented by a score of correct answers. Secondary outcomes were purchasing intentions and the healthiest-perceived product. Multinomial logistic regressions were performed. Results: The Nutri-Score V.2.0 increased the objective understanding of both the nutrient profile dimension (OR highest vs lowest score category=29.0 (23.4-35.9), p<0.001) and the ultraprocessing dimension (OR=174.3 (151.4-200.5), p<0.001). Trends were similar for cookies, breakfast cereals and ready-to-eat meals. The Nutri-Score V.2.0 had a positive effect on purchasing intentions and on the products perceived as the healthiest. Conclusion: This randomised controlled trial demonstrates the interest of a front-of-pack label combining the Nutri-Score (informing on the nutrient profile dimension) with an additional graphic mention, indicating when the food is ultraprocessed, compared with a no-label situation. Our results show that a combined label enabled participants to independently understand these two complementary dimensions of foods. Trial registration number: NCT05610930.

Artificial Sweeteners and Risk of Type 2 Diabetes in the Prospective NutriNet-Santé Cohort.

OBJECTIVE: To study the relationships between artificial sweeteners, accounting for all dietary sources (total and by type of artificial sweetener) and risk of type 2 diabetes (T2D), in a large-scale prospective cohort. RESEARCH DESIGN AND METHODS: The analyses included 105,588 participants from the web-based NutriNet-Santé study (France, 2009-2022; mean age 42.5 ± 14.6 years, 79.2% women). Repeated 24-h dietary records, including brands and commercial names of industrial products, merged with qualitative and quantitative food additive composition data, enabled artificial sweetener intakes to be accurately assessed from all dietary sources. Associations between artificial sweeteners (total, aspartame, acesulfame potassium [K], and sucralose) and T2D were investigated using Cox proportional hazard models adjusted for potential confounders, including weight variation during follow-up. RESULTS: During a median follow-up of 9.1 years (946,650 person-years, 972 incident T2D), compared with nonconsumers, higher consumers of artificial sweeteners (i.e., above the sex-specific medians of 16.4 mg/day in men and 18.5 mg/day in women) had higher risks of developing T2D (hazard ratio [HR] 1.69; 95% CI 1.45-1.97; P-trend <0.001). Positive associations were also observed for individual artificial sweeteners: aspartame (HR 1.63 [95% CI 1.38-1.93], P-trend <0.001), acesulfame-K (HR 1.70 [1.42-2.04], P-trend <0.001), and sucralose (HR 1.34 [1.07-1.69], P-trend = 0.013). CONCLUSIONS: Potential for reverse causality cannot be eliminated; however, many sensitivity analyses were computed to limit this and other potential biases. These findings of positive associations between artificial sweetener intakes and increased T2D risk strengthen the evidence that these additives may not be safe sugar alternatives. This study provides important insights in the context of on-going reevaluation of artificial sweeteners by health authorities worldwide.

Associations of meal timing, number of eating occasions and night-time fasting duration with incidence of type 2 diabetes in the NutriNet-Santé cohort.

BACKGROUND: Food intake plays a pivotal role in regulating circadian rhythms, which modulate glucose and lipid homeostasis. However, studies investigating the association of meal timing and type 2 diabetes (T2D) incidence are lacking. The objective of this study was to investigate the longitudinal associations of meal timing, number of eating occasions and night-time fasting duration with incidence of T2D. METHODS: In total, 103 312 adults [79% women, mean age at baseline = 42.7 (SD = 14.6)] from the NutriNet-Santé cohort (2009-21) were included. Participants' meal timings and frequency were assessed using repeated 24-h dietary records and averaged from the first 2 years of follow-up (5.7 records/participant). Associations of meal timing, number of eating occasions and night-time fasting duration with incidence of T2D were assessed by using multivariable Cox proportional hazard models adjusted for known risk factors. RESULTS: During a median follow-up of 7.3 years, 963 new cases of T2D were ascertained. Compared with participants habitually having a first meal before 8AM, those eating after 9AM had a higher incidence of T2D (HR = 1.59, 95% CI 1.30-1.94). Time of last meal was not associated with T2D incidence. Each additional eating episode was associated with a lower incidence of T2D (HR = 0.95, 95% CI 0.90-0.99). Night-time fasting duration was not associated with T2D incidence, except in participants having breakfast before 8AM and fasting for >13 h overnight (HR = 0.47, 95% CI 0.27-0.82). CONCLUSIONS: In this large prospective study, a later first meal was associated with a higher incidence of T2D. If confirmed in other large-scale studies, an early breakfast should be considered in preventing T2D.

IGF-1 and Risk of Morbidity and Mortality From Cancer, Cardiovascular Diseases, and All Causes in EPIC-Heidelberg.

CONTEXT: The functional status of organs, such as the liver, involved in IGF-1 signaling pathways influences circulating levels of IGF-1 and hence its relationship to risk of chronic disease and mortality, yet this has received limited attention. OBJECTIVE: To examine the relationship between IGF-1 and risk of morbidity and mortality from cancer, cardiovascular diseases (CVD), and all causes, accounting for liver function. METHODS: This study was a case-cohort design nested within EPIC-Heidelberg. IGF-1 was measured in 7461 stored serum samples collected from 1994 to 1998. Median follow-up for incident mortality events was 17.5 years. The case-cohort included a subcohort of 1810 men and 1890 women, in addition to 1668 incident cases of cancer (623 breast, 577 prostate, 202 lung, and 268 colorectal), and 1428 cases of CVD (707 myocardial infarctions and 723 strokes) and 2441 cases of death. RESULTS: Higher IGF-1 levels showed direct associations with risks of breast (1.25; 95% CI [1.06-1.47]) and prostate (1.31; [1.09-1.57]) cancers. Restricted cubic splines plots and models including IGF-1 as quintiles revealed a U-shaped relationship between the biomarker and mortality. Participants with the lowest and the highest levels of IGF-1 experienced higher hazards of mortality from cancer, CVD, and all causes. The U-shaped form of the relationship persisted but was attenuated in analyses including only participants without any indications of liver dysfunction. CONCLUSION: This large population-based prospective study showed that both individuals with lowest and highest levels of circulating IGF-1 were at increased risk of deaths from cancer, CVD, and all causes. For individuals with low IGF-1, the excess risks of death were more pronounced among individuals with liver cancer and cirrhosis but were also present among individuals without elevated liver enzymes.

Food processing and cancer risk in Europe: results from the prospective EPIC cohort study.

BACKGROUND: Food processing has been hypothesised to play a role in cancer development; however, data from large-scale epidemiological studies are scarce. This study investigated the association between dietary intake according to amount of food processing and risk of cancer at 25 anatomical sites using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: This study used data from the prospective EPIC cohort study, which recruited participants between March 18, 1991, and July 2, 2001, from 23 centres in ten European countries. Participant eligibility within each cohort was based on geographical or administrative boundaries. Participants were excluded if they had a cancer diagnosis before recruitment, had missing information for the NOVA food processing classification, or were within the top and bottom 1% for ratio of energy intake to energy requirement. Validated dietary questionnaires were used to obtain information on food and drink consumption. Participants with cancer were identified using cancer registries or during follow-up from a combination of sources, including cancer and pathology centres, health insurance records, and active follow-up of participants. We performed a substitution analysis to assess the effect of replacing 10% of processed foods and ultra-processed foods with 10% of minimally processed foods on cancer risk at 25 anatomical sites using Cox proportional hazard models. FINDINGS: 521 324 participants were recruited into EPIC, and 450 111 were included in this analysis (318 686 [70·8%] participants were female individuals and 131 425 [29·2%] were male individuals). In a multivariate model adjusted for sex, smoking, education, physical activity, height, and diabetes, a substitution of 10% of processed foods with an equal amount of minimally processed foods was associated with reduced risk of overall cancer (hazard ratio 0·96, 95% CI 0·95-0·97), head and neck cancers (0·80, 0·75-0·85), oesophageal squamous cell carcinoma (0·57, 0·51-0·64), colon cancer (0·88, 0·85-0·92), rectal cancer (0·90, 0·85-0·94), hepatocellular carcinoma (0·77, 0·68-0·87), and postmenopausal breast cancer (0·93, 0·90-0·97). The substitution of 10% of ultra-processed foods with 10% of minimally processed foods was associated with a reduced risk of head and neck cancers (0·80, 0·74-0·88), colon cancer (0·93, 0·89-0·97), and hepatocellular carcinoma (0·73, 0·62-0·86). Most of these associations remained significant when models were additionally adjusted for BMI, alcohol and dietary intake, and quality. INTERPRETATION: This study suggests that the replacement of processed and ultra-processed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types. FUNDING: Cancer Research UK, l'Institut National du Cancer, and World Cancer Research Fund International.

ABO blood types and SARS-CoV-2 infection assessed using seroprevalence data in a large population-based sample: the SAPRIS-SERO multi-cohort study.

ABO blood type has been reported as a potential factor influencing SARS-CoV-2 infection, but so far mostly in studies that involved small samples, selected population and/or used PCR test results. In contrast our study aimed to assess the association between ABO blood types and SARS-CoV-2 infection using seroprevalence data (independent of whether or not individuals had symptoms or sought for testing) in a large population-based sample. Our study included 67,340 French participants to the SAPRIS-SERO multi-cohort project. Anti-SARS-CoV-2 antibodies were detected using ELISA (targeting the proteins spike (S) and nucleocapsid (NP)) and seroneutralisation (SN) tests on dried blood spots collected in May-November 2020. Non-O individuals (and especially types A and AB) were more likely to bear anti SARS-CoV-2 antibodies (ELISA-S, 2964 positive cases: ORnon-Ovs.O = 1.09[1.01-1.17], ORAvs.O = 1.08[1.00-1.17]; ELISA-S/ELISA-NP/SN, 678 triple positive cases: ORnon-Ovs.O = 1.19 [1.02-1.39], ORAvs.O = 1.19[1.01-1.41], ORABvs.O = 1.43[1.01-2.03]). Hence, our results provided additional insights into the dynamic of SARS-CoV-2 infection, highlighting a higher susceptibility of infection for individuals of blood types A and AB and a lesser risk for blood type O.