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.

Early childcare and developmental delay risk at 3.5 years: Insights from the French ELFE cohort.

We tested the association between early childcare attendance in the first three years of life and child development at age 3.5 years in the French context, where early childcare is subsidized. In the ELFE (Étude Longitudinale Français depuis l'Enfance) birth cohort study set in metropolitan France, children's development was reported by parents at age 3.5 years (n = 11,033) via the Child Development Inventory (CDI) questionnaire. CDI scores were transformed into a development quotient (DQ), with a DQ < 90 corresponding to possible and a DQ < 85 corresponding to a probable developmental delay. Inverse probability weighted multivariable regression models were used to analyse whether early childcare in the first three years of life (centre-based, childminder, informal or parental care) was associated to development delay. Compared to children in exclusive parental care, those in centre-based childcare (CBC) or with a childminder prior to school entry were significantly less likely to experience possible (OR = 0.56, [95% CI = 0.51-0.61] for CBC and OR = 0.77, [95% CI = 0.72-0.83] for childminder attendance) and probable developmental delay (OR = 0.62, [0.58-0.67] for CBC and OR = 0.80 [0.76-0.83] for childminder). Informal childcare attendance was not significantly associated with children's possible nor probable developmental delay ((OR = 0.97, [0.84-1.12]) and (OR = 0.97, [0.82-1.15]), respectively). Conclusions: Overall, our findings add to the existing scientific literature, showing that in the French context, where childcare can start as early as 3 months of age, early childcare attendance can contribute to child's development. What's Known on This Subject: • Studies on early childcare attendance and child development have shown mixed results, associations with better psychomotor development mainly being observed in Nordic countries, while some studies in other countries such as the USA showed no or negative associations. What This Study Adds: • In a country with broad and subsidized access to childcare such as France, access to early childhood education can positively contribute to children's psychomotor development. However, we found that access to childcare does not appear to reduce social inequalities in children's psychomotor development.

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).

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.

Public perception of the tax on sweetened beverages in France.

OBJECTIVE: To assess in 2021 the acceptance and perception of the French tax on sweetened beverages, following its revision in 2018, and factors associated with a higher level of acceptance. DESIGN: A cross-sectional survey within the NutriNet-Santé cohort study. Participants were invited to complete a self-reported questionnaire in March 2021. Weighting was applied to the sample to allow inferences on the French population. Individual characteristics associated with support for the tax were investigated using logistic regression modelling. SETTINGS: NutriNet-Santé prospective cohort study. PARTICIPANTS: Adults engaged in the NutriNet-Santé cohort, aged 18 years or older (n 28 344), living in mainland France. RESULTS: Almost two-thirds (63·4 %) of the participants were aware of the existence of a tax on sweetened beverages, although less than a quarter had specific knowledge regarding its design and the 2018 revision. In turn, 64·7 % of participants expressed a favourable opinion towards the taxation scheme. This proportion was higher if tax revenues were used to finance health-related measures (respectively 68·8 % of favourable opinion if used to finance a reduction in prices of healthy products and 76·4 % if used to finance the healthcare system). Multivariable analyses showed that support towards the tax varied among subgroups of the population. Groups who tended to be less financially affected by the measure and those who perceived sugar-sweetened beverages as having detrimental effects were more likely to support the tax. CONCLUSION: The revised French sugar-sweetened beverage tax appeared to be favourably received and perceived by the public.

Anxiety is a potential effect modifier of the association between red and processed meat consumption and cancer risk: findings from the NutriNet-Santé cohort.

PURPOSE: Red and processed meats are recognized by the International Agency for Research on Cancer as probably carcinogenic and carcinogenic to humans, respectively. Heme iron has been proposed as a central factor responsible for this effect. Furthermore, anxiety affects the intestinal barrier function by increasing intestinal permeability. The objective of this work was to assess how anxiety modifies the association between red and processed meat consumption and cancer risk in the NutriNet-Santé prospective cohort (2009-2019). METHODS: Using multi-adjusted Cox models in a sample of 101,269 subjects, we studied the associations between the consumption of red and processed meat, the amount of heme iron coming from these meats and overall, colorectal, prostate, and breast cancer risks, overall and separately among participants with and without anxiety. RESULTS: An increase in red and processed meat consumption was associated with an increased risk of developing colorectal cancer in the total population (HR for an increase of 50 g/day = 1.18 (1.01-1.37), p = 0.03). After stratification on anxiety, the HR 50 g/day was 1.42 (1.03-1.94, p = 0.03) in anxious participants and 1.12 (0.94-1.33, p = 0.20) in other participants. Similar trends were observed for overall cancer risk. Analyses conducted with heme iron also provided similar results. CONCLUSIONS: Our results strengthen the existing body of evidence supporting that red and processed meat consumption and heme iron intake are associated with an increased risk of overall and more specifically colorectal cancer, and suggest that anxiety modifies these associations, with an increased risk in anxious participants.

Ultra-processed food intake in association with BMI change and risk of overweight and obesity: A prospective analysis of the French NutriNet-Santé cohort.

BACKGROUND: Ultra-processed food (UPF) consumption has increased drastically worldwide and already represents 50%-60% of total daily energy intake in several high-income countries. In the meantime, the prevalence of overweight and obesity has risen continuously during the last century. The objective of this study was to investigate the associations between UPF consumption and the risk of overweight and obesity, as well as change in body mass index (BMI), in a large French cohort. METHODS AND FINDINGS: A total of 110,260 adult participants (≥18 years old, mean baseline age = 43.1 [SD 14.6] years; 78.2% women) from the French prospective population-based NutriNet-Santé cohort (2009-2019) were included. Dietary intakes were collected at baseline using repeated and validated 24-hour dietary records linked to a food composition database that included >3,500 different food items, each categorized according to their degree of processing by the NOVA classification. Associations between the proportion of UPF in the diet and BMI change during follow-up were assessed using linear mixed models. Associations with risk of overweight and obesity were assessed using Cox proportional hazard models. After adjusting for age, sex, educational level, marital status, physical activity, smoking status, alcohol intake, number of 24-hour dietary records, and energy intake, we observed a positive association between UPF intake and gain in BMI (ß Time × UPF = 0.02 for an absolute increment of 10 in the percentage of UPF in the diet, P < 0.001). UPF intake was associated with a higher risk of overweight (n = 7,063 overweight participants; hazard ratio (HR) for an absolute increase of 10% of UPFs in the diet = 1.11, 95% CI: 1.08-1.14; P < 0.001) and obesity (n = 3,066 incident obese participants; HR10% = 1.09 (1.05-1.13); P < 0.001). These results remained statistically significant after adjustment for the nutritional quality of the diet and energy intake. Study limitations include possible selection bias, potential residual confounding due to the observational design, and a possible item misclassification according to the level of processing. Nonetheless, robustness was tested and verified using a large panel of sensitivity analyses. CONCLUSIONS: In this large observational prospective study, higher consumption of UPF was associated with gain in BMI and higher risks of overweight and obesity. Public health authorities in several countries recently started to recommend privileging unprocessed/minimally processed foods and limiting UPF consumption. TRIAL REGISTRATION: ClinicalTrials.gov NCT03335644 (https://clinicaltrials.gov/ct2/show/NCT03335644).

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.

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.

Nitrites, Nitrates, and Cardiovascular Outcomes: Are We Living "La Vie en Rose" With Pink Processed Meats?

Background Nitrates and nitrites are used as food additives in processed meats. They are also commonly ingested from water and several foods. Several short-term clinical studies suggested beneficial effects of dietary nitrates on blood pressure, while deleterious effects on oxidative damage have been suggested in some experimental studies. However, there is a lack of evidence from longitudinal epidemiological studies linking foods and water-originated and additives-originated nitrites and nitrates, separately, to hypertension and cardiovascular diseases risk. We aimed to study these associations in a large population-based cohort. Methods and Results Overall, 106 288 adults from the French NutriNet-Santé cohort (2009-2022) were included. Associations between nitrites and nitrates intakes and hypertension and cardiovascular disease risks were assessed using multi-adjusted Cox proportional hazard models. During follow-up, 3810 incident cases of hypertension and 2075 cases of cardiovascular diseases were ascertained. Participants with higher intakes of additives-originated nitrites (sodium nitrite in particular [European code e250]) had a higher hypertension risk compared with nonconsumers (hazard ratio, 1.19 [95% CI, 1.08-1.32], P=0.001, and 1.19 [95% CI, 1.08-1.32], P=0.002), respectively. No association was detected between foods and water-originated nitrites, or nitrates with hypertension risk (all P values >0.3). We found no association between nitrites or nitrates and risks of cardiovascular diseases (all P values >0.2). Conclusions These results do not support a protective role of nitrites or nitrates in cardiovascular health. Instead, they suggest a positive association between nitrites from food additives and hypertension risk, which needs confirmation in other large-scale studies. These findings provide new evidence in the context of current discussions about updating regulations on the use of nitrites as food additives.

Glycaemic index, glycaemic load and cancer risk: results from the prospective NutriNet-Santé cohort.

BACKGROUND: Evidence is accumulating that high dietary glycaemic index (GI) and glycaemic load (GL) are potential risk factors for several metabolic disorders (e.g. type-2 diabetes, cardiovascular diseases), but remains limited concerning cancer risk. Although, mechanistic data suggest that consuming high-GI foods may contribute to carcinogenesis through elevated blood glucose levels, insulin resistance or obesity-related mechanisms. Our objective was to study the associations between dietary GI/GL and cancer. METHODS: In total, 103 020 French adults (median age = 40.2 years) from the NutriNet-Santé cohort (2009-2020) with no cancer or diabetes at baseline were included (705 137 person-years, median follow-up time = 7.7 years). Repeated 24-h dietary records linked with a detailed food-composition table (>3500 food/beverage items). We computed the average dietary GI and GL at the individual level. Associations between GI, GL, contribution of low- and medium/high-GI foods to energy and carbohydrate intake and cancer risk (overall, breast, prostate and colorectal) were assessed using multivariable Cox proportional-hazard models. RESULTS: Higher dietary GL was associated with higher overall cancer risk [n = 3131 cases, hazard ratios (HRs) for sex-specific quintile 5 vs 1 = 1.25, 95% confidence interval (CI) = 1.03-1.52; Ptrend = 0.008] and specifically postmenopausal breast cancer (n = 924, HRQ5vs.Q1 = 1.64, 95% CI = 1.06-2.55; Ptrend = 0.03). A higher contribution of low-GI food/beverages to energy intake was associated with lower cancer risk whereas a higher contribution of medium/high-GI items to energy intake was positively associated with higher risk of overall, breast and postmenopausal breast cancers (Ptrend ≤ 0.02). CONCLUSIONS: These results support a possible impact of GI/GL on cancer risk. If confirmed in other populations and settings, dietary GI/GL could be considered as modifiable risk factors for primary cancer prevention. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03335644.

Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort.

OBJECTIVES: To study the associations between artificial sweeteners from all dietary sources (beverages, but also table top sweeteners, dairy products, etc), overall and by molecule (aspartame, acesulfame potassium, and sucralose), and risk of cardiovascular diseases (overall, coronary heart disease, and cerebrovascular disease). DESIGN: Population based prospective cohort study (2009-21). SETTING: France, primary prevention research. PARTICIPANTS: 103 388 participants of the web based NutriNet-Santé cohort (mean age 42.2±14.4, 79.8% female, 904 206 person years). Dietary intakes and consumption of artificial sweeteners were assessed by repeated 24 h dietary records, including brand names of industrial products. MAIN OUTCOMES MEASURES: Associations between sweeteners (coded as a continuous variable, log10 transformed) and cardiovascular disease risk, assessed by multivariable adjusted Cox hazard models. RESULTS: Total artificial sweetener intake was associated with increased risk of cardiovascular diseases (1502 events, hazard ratio 1.09, 95% confidence interval 1.01 to 1.18, P=0.03); absolute incidence rate in higher consumers (above the sex specific median) and non-consumers was 346 and 314 per 100 000 person years, respectively. Artificial sweeteners were more particularly associated with cerebrovascular disease risk (777 events, 1.18, 1.06 to 1.31, P=0.002; incidence rates 195 and 150 per 100 000 person years in higher and non-consumers, respectively). Aspartame intake was associated with increased risk of cerebrovascular events (1.17, 1.03 to 1.33, P=0.02; incidence rates 186 and 151 per 100 000 person years in higher and non-consumers, respectively), and acesulfame potassium and sucralose were associated with increased coronary heart disease risk (730 events; acesulfame potassium: 1.40, 1.06 to 1.84, P=0.02; incidence rates 167 and 164; sucralose: 1.31, 1.00 to 1.71, P=0.05; incidence rates 271 and 161). CONCLUSIONS: The findings from this large scale prospective cohort study suggest a potential direct association between higher artificial sweetener consumption (especially aspartame, acesulfame potassium, and sucralose) and increased cardiovascular disease risk. Artificial sweeteners are present in thousands of food and beverage brands worldwide, however they remain a controversial topic and are currently being re-evaluated by the European Food Safety Authority, the World Health Organization, and other health agencies. 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.

Ultra-processed food intake and eating disorders: Cross-sectional associations among French adults.

Background and aims: Data regarding the association between ultra-processed food (UPF) consumption and eating disorders (ED) are scarce. Our aim was to investigate whether UPF intake was associated with different ED types in a large population-based study. Methods: 43,993 participants (mean age = 51.0 years; 76.1% women) of the French NutriNet-Santé web-cohort who were screened for ED in 2014 via the Sick-Control-One stone-Fat-Food (SCOFF) questionnaire, were included in the analysis. The clinical algorithm Expali TM tool was used to identify four ED types: restrictive, bulimic, binge eating, and other (not otherwise specified). Mean dietary intake was evaluated from at least 2 self-administered 24-h dietary records (2013-2015); categorization of food as ultra-processed or not relied on the NOVA classification. The associations between UPF intake (as percent and reflecting mean daily UPF quantity (g/d) within the dietary intake, %UPF) and ED types were evaluated using polytomous logistic regression models. Results: 5,967 participants (13.6%) were categorized as likely ED (restrictive n = 444; bulimic n = 1,575; binge eating n = 3,124; other ED n = 824). The fully-adjusted analyses revealed a positive association between UPF intake and bulimic, binge eating, and other ED: ED risk (odds ratio, OR) for an absolute 10-percentage point incremental increase in %UPF intake were 1.08 (1.01-1.14; P = 0.02), 1.21 (1.16-1.26; P < 0.0001), and 1.11 (1.02-1.20; P = 0.02), respectively. No significant association was detected for restrictive ED. Discussion and Conclusion: This study revealed an association of UPF intake with different ED types among French adults. Future research is needed to elucidate the direction of the observed associations.

[Ultra-processed food : from research to guidelines]. / Aliments ultra-ransformés : de la recherche aux recommandations.

Ultra-processed food : from research to guidelinesduring the past decades, food systems have shifted towards an important increase in the degree of food processing and formulation. Ultra-processed foods are products that have undergone complex processing techniques ( physical, chemical, or biological ), having a possible Impact on food matrix, and often contain cosmetic food additives (emulsifiers, sweeteners, coloring agents…) and industrial substances derived from foods (maltodextrin, hydrogenated oils, modified starches…). Several characteristics of ultra-processed foods have triggered the scientific community to investigate their potential impact on long-term human health: a lower nutritional quality compared with unprocessed or minimally Processed foods, food additives for some of which possible adverse effects have been suggested in preclinical In vitro / in vivo studies, contaminants issued from processing techniques or packaging, and modifications in the food matrix and textures, leading to increased energy intake rate and overconsumption. Dozens of prospective Studies around the world have shown associations between the consumption of these products and higher risks of chronic diseases (e.g. Cancer, cardiovascular disease, type-2 diabetes, obesity) and mortality. Public health authorities in France and other countries now recommend limiting the consumption of these products. However, further research is needed to better understand the underlying mechanisms and pertinently guide regulating The use of certain substances and additives, and industrial reformulation processes.

Aliments ultra-transformés : de la recherche aux recommandations Au cours des dernières décennies, les systèmes alimen¬taires ont connu une augmentation importante du degré de transformation et de formulation des produits. Les aliments dits « ultratransformés ¼ ont subi d'intenses processus de transformation (biologique, chimique, phy¬sique), susceptibles d'impacter largement les matrices alimentaires, et contiennent généralement des additifs (colorants, exhausteurs de goût, édulcorants, émulsifiants, etc.) Ou d'autres ingrédients typiquement industriels (maltodextrine, huiles hydrogénées, etc.). Plusieurs de leurs caractéristiques ont incité les chercheurs à inves¬tiguer l'impact de leur consommation sur la santé : moindre qualité nutritionnelle en moyenne, présence d'additifs pour lesquels des études précliniques in vitro/in vivo ont suggéré certains effets nocifs, présence de contaminants issus des procédés de transformation ou des emballages, texture et propriétés sensorielles incitant à la surconsommation, etc. Ces dernières années, des dizaines d'études prospectives dans le monde ont obser¬vé des associations entre la consommation de ces pro¬duits et des risques plus élevés de maladies chroniques (cancer, maladies cardiovasculaires, diabète, obésité…) et la mortalité. En france et dans d'autres pays, les au¬torités de santé publique recommandent donc désormais de limiter leur consommation. Des travaux de recherche sont nécessaires afin de mieux comprendre les subs¬tances, procédés et mécanismes en jeu et d'orienter la réglementation sur l'usage de certains ingrédients, addi¬tifs ou pratiques de transformation.

Consumption of Ultra-Processed Food and Its Association with Sociodemographic Characteristics and Diet Quality in a Representative Sample of French Adults.

The present study aims to describe ultra-processed food (UPF) consumption in a representative sample of French adults and to evaluate the association between UPF consumption and socioeconomic characteristics and nutritional profile of the diet. This is a cross-sectional study using food consumption data from the Étude Nationale Nutrition Santé (ENNS), conducted with 2642 participants (18-74 years old), between February 2006 and March 2007 in France. Dietary data were collected through three 24-h dietary recalls. All food and beverages were classified according to the NOVA classification. The energy contribution of NOVA food groups to total energy intake was presented by categories of sociodemographic characteristics. Linear and logistic regression models were used to estimate the association between the percentage of UPF in the diet with nutritional indicators. The mean daily energy consumption of the adult French population was 2111 kcal, of which 31.1% came from UPF. This percentage was higher among younger individuals, and in the urban area, and lower among individuals with incomplete high school and individuals who were retired. The consumption of UPF was positively associated with the dietary energy density and the dietary contents of total carbohydrates, free sugar, and total and saturated fat, as well as with inadequate dietary energy density, saturated fat, free sugar, and fiber intakes.

Exposure to food additive mixtures in 106,000 French adults from the NutriNet-Santé cohort.

Food additives (e.g. artificial sweeteners, emulsifiers, dyes, etc.) are ingested by billions of individuals daily. Some concerning results, mainly derived from animal and/or cell-based experimental studies, have recently emerged suggesting potential detrimental effects of several widely consumed additives. Profiles of additive exposure as well as the potential long-term impact of multiple exposure on human health are poorly documented. This work aimed to estimate the usual intake of food additives among participants of the French NutriNet-Santé cohort and to identify and describe profiles of exposure (single substances and mixtures). Overall, 106,489 adults from the French NutriNet-Santé cohort study (2009-ongoing) were included. Consumption of 90 main food additives was evaluated using repeated 24 h dietary records including information on brands of commercial products. Qualitative information (as presence/absence) of each additive in food products was determined using 3 large-scale composition databases (OQALI, Open Food Facts, GNPD), accounting for the date of consumption of the product. Quantitative ingested doses were estimated using a combination of laboratory assays on food matrixes (n = 2677) and data from EFSA and JECFA. Exposure was estimated in mg per kg of body weight per day. Profiles of exposure to food additive mixtures were extracted using Non-negative Matrix Factorization (NMF) followed by k-means clustering as well as Graphical Lasso. Sociodemographic and dietary comparison of clusters of participants was performed by Chi-square tests or linear regressions. Data were weighted according to the national census. Forty-eight additives were consumed by more than 10% of the participants, with modified starches and citric acid consumed by more than 90%. The top 50 also included several food additives for which potential adverse health effects have been suggested by recent experimental studies: lecithins (86.6% consumers), mono- and diglycerides of fatty acids (78.1%), carrageenan (77.5%), sodium nitrite (73.9%), di-, tri- and polyphosphates (70.1%), potassium sorbate (65.8%), potassium metabisulphite (44.8%), acesulfame K (34.0%), cochineal (33.9%), potassium nitrate (31.6%), sulfite ammonia caramel (28.8%), bixin (19.5%), monosodium glutamate (15.1%) and sucralose (13.5%). We identified and described five clusters of participants more specifically exposed to five distinct additive mixtures and one additional cluster gathering participants with overall low additive exposure. Food additives, including several for which health concerns are currently debated, were widely consumed in this population-based study. Furthermore, main mixtures of additives were identified. Their health impact and potential cocktail effects should be explored in future epidemiological and experimental studies.