Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice.

ABSTRACT: Fostamatinib, a recently approved Syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here, 138 patients with ITP (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range [IQR], 56-80). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166). The median number of therapies before fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%), and IV immunoglobulins (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month before treatment initiation. Seventy-nine percent of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 × 109/L). Eighty-three patients (60.1%) received fostamatinib monotherapy, achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1 to 2; the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis, and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.

Statin therapy is associated with lower prevalence of gut microbiota dysbiosis.

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics.

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.

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.

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries.

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus.

A randomized controlled trial to test the effects of displaying the Nutri-Score in food advertising on consumer perceptions and intentions to purchase and consume.

BACKGROUND: Some research shows that advertising for high-fat, sugar, or salt (HFSS) products is contributing to a shift in consumer preferences toward products of poor nutritional quality, leading to unhealthy nutritional intakes that increase the risk of obesity and chronic diseases. A strategy of displaying simple and understandable nutritional information (like the front-of-pack nutrition label Nutri-Score) in food messages could be an aid to help guide consumers' choice towards healthier products. METHODS: A randomized controlled experiment was conducted on 27,085 participants randomly assigned to two experimental conditions or a control condition. In both experimental conditions (independent variable: advertising messages with vs. without the Nutri-Score), participants were exposed to advertisements for diversified food products with contrasting nutritional quality and belonging to nine different food categories. Participants were then asked questions about their perception, affective evaluation, and intentions to purchase and consume the products. In the control condition, they were not exposed to the advertisements. RESULTS: Overall, interaction effects between the two variables (1) the messages with vs. without the Nutri-Score and (2) the nutritional quality of products, were significant for all dependent variables, with effect sizes between large and medium. Overall, the better the products' nutritional quality, the more positive their perceptions, affective evaluations, and intentions to buy and consume them. When the Nutri-score was displayed in advertising messages (vs. when it was not), perceptions, affective evaluation, and behavioral intentions: (1) became more positive for products of good nutritional quality (Nutri-score A and B), (2) became more negative for products of poor nutritional quality (Nutri-score D and E), (3) changed little or not at all for products of intermediate nutritional quality (Nutri-Score C). CONCLUSIONS: This research is the first in the literature to demonstrate that displaying the Nutri-Score in advertising messages assists consumers in directing their choices towards healthier foods. Regulations mandating the display of the Nutri-Score in food advertising could be an effective public health measure.

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 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).

Respective contribution of ultra-processing and nutritional quality of foods to the overall diet quality: results from the NutriNet-Santé study.

BACKGROUND: Both the nutritional quality of the foods consumed (as nutrient composition) and their ultra-processed nature have been linked to health risks. However, the respective contribution of each of these correlated dimensions or their synergy to the overall diet quality has been rarely explored. OBJECTIVE: To identify the respective effects of the nutritional quality of the foods consumed, the ultra-processed nature of foods and their cross-effect contributing to the overall quality of the diet. DESIGN: Cross-sectional observational study. SETTING: Web-based French NutriNet-Santé cohort study. PARTICIPANTS: Participants in the NutriNet-Santé cohort study with at least three available 24 h records as baseline dietary data (N = 98 454 participants). MAIN OUTCOME MEASURES: The overall quality of the diet (qualified using the adherence to the 2017 French national nutrition and health dietary recommendations dietary score PNNS-GS2) was broken down into: (1) an effect of the nutritional quality of the foods consumed (qualified using the modified Foods Standards Agency nutrient profile model (underlying the Nutri-Score) dietary index FSAm-NPS DI); (2) an effect of the ultra-processed nature of the foods consumed (qualified using the proportion of ultra-processed foods consumed UPFp using the NOVA classification), and (3) a cross-effect of both dimensions. RESULTS: The overall effect from the 'nutritional quality of the foods consumed' (FSAm-NPS DI) was 1.10, corresponding to 26% of the total effect; the overall effect from ultra-processed foods consumption was 1.29, corresponding to 30% of the total effect; and cross-effect between nutritional quality of the foods consumed and ultra-processing was at 1.91, corresponding to 44% of total effects. CONCLUSIONS: Our study provides support to the postulate that nutritional quality and ultra-processing should be considered as two correlated but distinct and complementary dimensions of the diet.

Cross-sectional comparisons of dietary indexes underlying nutrition labels: nutri-score, Canadian 'high in' labels and Diabetes Canada Clinical Practices (DCCP).

PURPOSE: To assess the cross-sectional association between dietary indexes (DI) that underlie, respectively, the Nutri-score (NS), the proposed Canadian 'High In' Symbol (CHIL) and the Diabetes Canada Clinical Practice Guidelines (DCCP) with food consumption, nutrient intakes and metabolic markers. METHODS: 1836 adults (18-74 years) participating in the representative ESTEBAN study, conducted in mainland France in 2014-2016, were included in the analysis. Food consumption was assessed with three repeated 24 h dietary recalls. Anthropometric measurements and biomarkers of metabolic risk (cholesterol-total, LDL (Low Density Lipoprotein), HDL (High Density Lipoprotein)-triglycerides, glucose) were obtained through a clinical examination and fasting blood draw. The DI were assessed for their association with food consumption, dietary intakes and metabolic biomarkers as quintiles and continuous variables using multi-adjusted linear regression. Heathier diets were assigned to lower scores. RESULTS: Correlations between scores ranged from + 0.62 between CHIL-DI and NS-DI to + 0.75 between NS-DI and DCCP-DI. All DIs discriminated individuals according to the nutritional quality of their diets through food consumption and nutrient intakes (healthier diets were associated with lower intakes of energy, added sugars and saturated fat; and with higher intakes of fiber, vitamins and minerals). NS-DI was associated with blood glucose (adjusted mean in Q1 = 5 vs. Q5 = 5.46 mmol/dl, ptrend = 0.001) and DCCP-DI was associated with BMI (Q1 = 24.8 kg/m2 vs. Q5 = 25.8 kg/m2, ptrend = 0.025), while CHIL showed no significant association with any anthropometric measures or biomarkers. CONCLUSIONS: This study provides elements supporting the validity of the nutrient profiling systems underlying front-of-package nutrition labellings (FOPLs) to characterize the healthiness of diets.

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.

Comparative understanding and preference of Nutri-Score and NutrInform Battery in a sample of Spanish consumers.

BACKGROUND: Interpretive front-of-pack labels (FoPLs) are supported by World Health Organization as an important policy tool to promote healthy diets. At present, various FoPLs formats co-exist in the European Union (EU). However, as part of the Farm to Fork strategy published in 2020, the European Commission stated that it would propose a single mandatory FoPL. The aim of this study was to analyze Spanish consumers' preference and objective understanding of Nutri-Score and NutrInform, two FoPLs that are currently the subject of debate in the EU. METHODS: In a representative sample of 1026 Spanish adults (50% women, mean age ± SD = 46 ± 14 years), objective understanding was assessed by asking participants to identify the healthiest food products in three food categories (breakfast products, breakfast cereals and added fats). The preference dimensions were tested by asking participants about the perceived helpfulness of the FoPL in discriminating the nutritional quality of food products (subjective understanding) and their overall assessment of the FoPL's ease of use, informativeness, trust and liking (perception). RESULTS: In terms of objective understanding, Nutri-Score was significantly associated with an increase in consumers' ability to identify healthier food products across all food categories compared with NutrInform [OR (odds ratio) = 19.1 [14.2-25.7], P < 0.0001]. On the preference dimension, Nutri-Score was perceived as significantly easier to use and was more liked than NutrInform (standardized principal component analysis dimension, respectively, 0.32 ± 1.58 vs. -0.29 ± 1.66, P < 0.0001 and 0.080 ± 1.18 vs. -0.072 ± 1.17, P = 0.039). CONCLUSIONS: This study provides new evidence to support Nutri-Score in comparison with NutrInform in Spanish consumers, on both objective understanding and preference aspects.

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.

Dairy product consumption and risk of cancer: A short report from the NutriNet-Santé prospective cohort study.

The impact of dairy product consumption for long-term health remains unclear, in particular regarding their involvement in cancer etiology for frequent locations like breast or prostate. Besides, little is known about potentially different effects of dairy product subtypes. Our objective was therefore to evaluate the associations between dairy product consumption (total and subtypes) and cancer risk. A total of 101 279 participants from the French NutriNet-Santé cohort study were included (78.7% women; mean [SD] age = 42.2 [14.5] years). Dairy product consumption was assessed using validated web-based 24-hour dietary records. Multiadjusted Cox models were computed. After a median [interquartile range] follow-up time of 5.9 [2.7-8.3] years, we documented 2503 incident cancer cases (783 breast, 323 prostate and 182 colorectal cancers). Total dairy product consumption was not significantly associated with cancer. However, the consumption of "fromage blanc" (a French type of quark/cottage cheese) was associated with an increased risk of cancer overall (HR for 1 serving increment [95% CI] = 1.11 [1.01-1.21]; P-trend = .03) and of colorectal cancer (HR = 1.39 [1.09-1.77]; P-trend < .01). Besides, sugary dairy dessert consumption was directly associated with colorectal cancer risk (HR for 1 serving increment = 1.58 [1.01-2.46]; P-trend = .046]. No association was observed between the consumption of dairy products or sugary dairy desserts and the risk of prostate and breast cancers. In our study, the consumption of dairy products was not associated with the risk of overall, colorectal, breast or prostate cancers. The consumption of "fromage blanc" and sugary dairy desserts were associated to an increased risk of colorectal cancer, but this warrants further investigations.

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.

Are foods 'healthy' or 'healthier'? Front-of-pack labelling and the concept of healthiness applied to foods.

While food-based dietary guidelines have been widely disseminated for decades to improve nutritional knowledge in the population about healthy diets, more recent interventions such as front-of-pack labelling have made the differences between the two approaches apparent. While food-based dietary guidelines provide the overarching framework and benchmarks for a healthy diet, based on the current knowledge of the associations between various dietary components and health outcomes, front-of-pack labelling provides guidance to select a specific food, either within a food group or among similar foods belonging to various brands. Labelling foods as 'healthy' or 'unhealthy' raises multiple questions on the criteria used to define the terms and the implications of assigning an absolute healthiness value to an individual food in the context of complex diets. Gradual systems may provide more relative assessments and avoid dichotomisation. The present article presents the inherent differences and the complementarity of food-based dietary guidelines and food choice guidance in the context of food labelling.

Consumption of dairy products and CVD risk: results from the French prospective cohort NutriNet-Santé.

In France, dairy products contribute to dietary saturated fat intake, of which reduced consumption is often recommended for CVD prevention. Epidemiological evidence on the association between dairy consumption and CVD risk remains unclear, suggesting either null or inverse associations. This study aimed to investigate the associations between dairy consumption (overall and specific foods) and CVD risk in a large cohort of French adults. This prospective analysis included participants aged ≥18 years from the NutriNet-Santé cohort (2009-2019). Daily dietary intakes were collected using 24-h dietary records. Total dairy, milk, cheese, yogurts, fermented and reduced-fat dairy intakes were investigated. CVD cases (n 1952) included cerebrovascular disease (n 878 cases) and CHD (n 1219 cases). Multivariable Cox models were performed to investigate associations. This analysis included 104 805 French adults (mean age at baseline 42·8 (sd 14·6) years, mean follow-up 5·5 (sd 3·0) years, i.e. 579 155 person-years). There were no significant associations between dairy intakes and total CVD or CHD risks. However, the consumption of at least 160 g/d of fermented dairy (e.g. cheese and yogurts) was associated with a reduced risk of cerebrovascular diseases compared with intakes below 57 g/d (hazard ratio = 0·81 (95 % CI 0·66, 0·98), Ptrend = 0·01). Despite being a major dietary source of saturated fats, dairy consumption was not associated with CVD or CHD risks in this study. However, fermented dairy was associated with a lower cerebrovascular disease risk. Robust randomised controlled trials are needed to further assess the impact of consuming different dairy foods on CVD risk and potential underlying mechanisms.

A population-based study of macronutrient intake according to mental health status with a focus on pure and comorbid anxiety and eating disorders.

PURPOSE: Eating disorders (ED) and anxiety impact food choices. In addition, comorbid anxiety seems to increase ED symptoms and severity. However, the association between such comorbidity and dietary intake is unknown. This population-based, cross-sectional study aimed to assess macronutrient intake according to mental health status (i.e., no disorder, pure and comorbid anxiety and ED). METHODS: The study included N = 24,771 participants (74% female, mean age = 53.2 ± 13.7 years) in the NutriNet-Santé cohort, who completed once the trait subscale of the State-Trait Anxiety Inventory (STAI-T; high anxiety: ≥ 40 points) between 2013 and 2016 and the SCOFF questionnaire screening for ED in 2014. The Expali algorithm was applied to categorize ED (no ED; restrictive: RS; bulimic: BL; hyperphagic: HP; other ED). Participants were divided into ten groups by crossing their anxiety status (two groups: low or high) and their ED status (five groups). Macronutrient intakes were evaluated from ≥ 3 24-h dietary records. Analyses of covariance (ANCOVA) and Dunnett-Hsu tests (reference = no disorder) were performed. RESULTS: Significant differences in macronutrient intake were seen between the pure and comorbid forms, especially for RS and HP. Compared to the "no disorder" group, a significantly higher percentage of energy from carbohydrates, higher intakes of total carbohydrates, simple sugars, and plant-based protein, lower intakes of total fat, saturated and monounsaturated fatty acids, and cholesterol were observed in the comorbid anxiety + RS group, but not in the pure RS group. In contrast, significantly lower intakes of added sugar and plant-based protein, and a higher intake of cholesterol were observed in the pure HP group, but not in the comorbid anxiety + HP group. For BL and other ED, similar results were observed between the pure and comorbid forms. CONCLUSION: This large epidemiological study provided some support for differences in macronutrient intake between individuals with pure or comorbid anxiety and ED. Differences in intake were largely dependent on ED type. Future prospective studies and studies using clinically defined anxiety and ED are needed to elucidate causality as well as potential effect modification of the observed associations.