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.

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).

Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study.

BACKGROUND: Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive. METHODS: We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method. RESULTS: Of 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HRQ5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HRQ5vs.Q1:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HRQ5vs.Q1:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HRQ5vs.Q1:1.11, 95%CI:0.94, 1.31), heme (HRQ5vs.Q1:0.95; 95%CI:0.84, 1.07) or non-heme iron (HRQ5vs.Q1:1.03, 95%CI:0.88, 1.20). Substitution of heme with non-heme iron demonstrated lower CRC risk in men (HR:0.94; 95%CI: 0.89, 0.99). CONCLUSIONS: Our findings suggest potential sex-specific CRC risk associations for higher iron consumption that may differ by dietary sources.

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.

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.

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.

Diet-wide association study of 92 foods and nutrients and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study.

It is unclear whether diet, and in particular certain foods or nutrients, are associated with lung cancer risk. We assessed associations of 92 dietary factors with lung cancer risk in 327 790 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) per SD higher intake/day of each food/nutrient. Correction for multiple comparisons was performed using the false discovery rate and identified associations were evaluated in the Netherlands Cohort Study (NLCS). In EPIC, 2420 incident lung cancer cases were identified during a median of 15 years of follow-up. Higher intakes of fibre (HR per 1 SD higher intake/day = 0.91, 95% CI 0.87-0.96), fruit (HR = 0.91, 95% CI 0.86-0.96) and vitamin C (HR = 0.91, 95% CI 0.86-0.96) were associated with a lower risk of lung cancer, whereas offal (HR = 1.08, 95% CI 1.03-1.14), retinol (HR = 1.06, 95% CI 1.03-1.10) and beer/cider (HR = 1.04, 95% CI 1.02-1.07) intakes were positively associated with lung cancer risk. Associations did not differ by sex and there was less evidence for associations among never smokers. None of the six associations with overall lung cancer risk identified in EPIC were replicated in the NLCS (2861 cases), however in analyses of histological subtypes, inverse associations of fruit and vitamin C with squamous cell carcinoma were replicated in the NLCS. Overall, there is little evidence that intakes of specific foods and nutrients play a major role in primary lung cancer risk, but fruit and vitamin C intakes seem to be inversely associated with squamous cell lung cancer.

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.

A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC.

BACKGROUND & AIMS: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. METHODS: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. RESULTS: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04-1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04-1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93-0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90-0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90-0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92-0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93-0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons. CONCLUSIONS: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.

Associations between Resilience and Food Intake Are Mediated by Emotional Eating in the NutriNet-Santé Study.

BACKGROUND: Resilience, the ability to bounce back or recover from stress, has been associated with several health-related behaviors. However, data on food intake and emotional eating are lacking. OBJECTIVES: The objective of this cross-sectional study was to analyze the associations between resilience and diet quality and ultraprocessed food (UPF) and food group consumption, and to assess whether emotional eating was a mediator of these associations. METHODS: In 2017, 17,840 participants (73.5% female, mean age = 55.4 ± 14.0 y) of the NutriNet-Santé study completed the Brief Resilience Scale, the revised 21-item Three-Factor Eating Questionnaire, and ≥3 self-administered 24-h dietary records. Diet quality was assessed with the modified French National Nutrition and Health Program Guideline Score. Foods and beverages consumed were categorized according to their degree of processing by the NOVA classification. We assessed the association between resilience and emotional eating using linear regression models. We also assessed the mediating role of emotional eating in the associations between resilience and diet quality, energy intake, and UPF and food group consumption, controlling for sociodemographic characteristics. RESULTS: In our study, resilience was negatively associated with emotional eating (P < 0.0001). More resilient participants had greater overall diet quality, greater intakes of seafood, whole-grain foods, fats, unsalted oleaginous fruits, and alcoholic beverages, and lower intakes of UPFs, starchy foods, dairy desserts, sugary fatty products, and sugar and confectionery (all P < 0.05). Emotional eating was a mediator of the inverse associations between resilience and intake of energy, UPFs, dairy desserts, sugary fatty products, and of the positive associations between resilience and alcoholic beverages (all P < 0.05), with a 20-70% mediation. CONCLUSIONS: Our findings showed that resilience was associated with an overall better diet quality in the NutriNet-Santé population-based study. These associations were partially explained by emotional eating. These findings suggest that resilience should be considered in the promotion of healthy dietary habits.The study is registered at clinicaltrials.gov as #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.

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.

Ageing-related markers and risks of cancer and cardiovascular disease: a prospective study in the EPIC-Heidelberg cohort.

Biological age is an important risk factor for chronic diseases. We examined the associations between five markers of unhealthy ageing; Growth Differentiation Factor-15 (GDF-15), N-terminal pro-brain natriuretic peptide (NT-proBNP), glycated hemoglobin A1c (HbA1C), C-Reactive Protein (CRP) and cystatin-C; with risks of cancer and cardiovascular disease (CVD). We used a case-cohort design embedded in the EPIC-Heidelberg cohort, including a subcohort of 3792 participants along with 4867 incident cases of cancer and CVD. Hazard ratios (HRs) were computed and the strongest associations were used to build weighted multi-marker combinations, and their associations with cancer and CVD risks were tested. After adjusting for common confounders, we observed direct associations of GDF-15 with lung cancer risk, NT-proBNP with breast, prostate and colorectal cancers, HbA1C with lung, colorectal, and breast cancer risks, and CRP with lung and colorectal cancer risks. An inverse association was observed for GDF-15 and prostate cancer risk. We also found direct associations of all 5 markers with myocardial infarction (MI) risk, and of GDF-15, NT-proBNP, CRP and cystatin-C with stroke risk. A combination of the independently-associated markers showed a moderately strong association with the risks of cancer and CVD (HRQ4-Q1 ranged from 1.78[1.36, 2.34] for breast cancer, when combining NT-proBNP and HbA1C, to 2.87[2.15, 3.83] for MI when combining NT-proBNP, HbA1C, CRP and cystatin-C). This analysis suggests that combinations of biomarkers related to unhealthy ageing show strong associations with cancer risk, and corroborates published evidence on CVD risk. If confirmed in other studies, using these biomarkers could be useful for the identification of individuals at higher risk of age-related diseases.

Serum markers of biological ageing provide long-term prediction of life expectancy-a longitudinal analysis in middle-aged and older German adults.

BACKGROUND: lifestyle behaviours and chronic co-morbidities are leading risk factors for premature mortality and collectively predict wide variability in individual life expectancy (LE). We investigated whether a pre-selected panel of five serum markers of biological ageing could improve predicting the long-term mortality risk and LE in middle-aged and older women and men. METHODS: we conducted a case-cohort study (n = 5,789 among which there were 2,571 deaths) within the European Prospective Investigation into Cancer-Heidelberg cohort, a population cohort of middle-aged and older individuals, followed over a median duration of 18 years. Gompertz models were used to compute multi-adjusted associations of growth differentiation factor-15, N-terminal pro-brain natriuretic peptide, glycated haemoglobin A1c, C-reactive protein and cystatin-C with mortality risk. Areas under estimated Gompertz survival curves were used to estimate the LE of individuals using a model with lifestyle-related risk factors only (smoking history, body mass index, waist circumference, alcohol, physical inactivity, diabetes and hypertension), or with lifestyle factors plus the ageing-related markers. RESULTS: a model including only lifestyle-related factors predicted a LE difference of 16.8 [95% confidence interval: 15.9; 19.1] years in men and 9.87 [9.20; 13.1] years in women aged ≥60 years by comparing individuals in the highest versus the lowest quintiles of estimated mortality risk. Including the ageing-related biomarkers in the model increased these differences up to 22.7 [22.3; 26.9] years in men and 14.00 [12.9; 18.2] years in women. CONCLUSIONS: serum markers of ageing are potentially strong predictors for long-term mortality risk in a general population sample of older and middle-aged individuals and may help to identify individuals at higher risk of premature death, who could benefit from interventions to prevent further ageing-related health declines.

Dietary intake of advanced glycation endproducts and risk of hepatobiliary cancers: A multinational cohort study.

Advanced glycation endproducts (AGEs) may contribute to liver carcinogenesis because of their proinflammatory and prooxidative properties. Diet is a major source of AGEs, but there is sparse human evidence on the role of AGEs intake in liver cancer etiology. We examined the association between dietary AGEs and the risk of hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition prospective cohort (n = 450 111). Dietary intake of three AGEs, Nε -[carboxymethyl]lysine (CML), Nε -[1-carboxyethyl]lysine (CEL) and Nδ -[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), was estimated using country-specific dietary questionnaires linked to an AGEs database. Cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations between dietary AGEs and risk of hepatocellular carcinoma (HCC), gallbladder and biliary tract cancers were estimated using multivariable Cox proportional hazard regression. After a median follow-up time of 14.9 years, 255 cases of HCC, 100 cases of gallbladder cancer and 173 biliary tract cancers were ascertained. Higher intakes of dietary AGEs were inversely associated with the risk of HCC (per 1 SD increment, HR-CML  = 0.87, 95% CI: 0.76-0.99, HR-CEL  = 0.84, 95% CI: 0.74-0.96 and HR-MH-G1  = 0.84, 95% CI: 0.74-0.97). In contrast, positive associations were observed with risk of gallbladder cancer (per 1 SD, HR-CML  = 1.28, 95% CI: 1.05-1.56, HR-CEL  = 1.17; 95% CI: 0.96-1.40, HR-MH-G1  = 1.27, 95% CI: 1.06-1.54). No associations were observed for cancers of the intra and extrahepatic bile ducts. Our findings suggest that higher intakes of dietary AGEs are inversely associated with the risk of HCC and positively associated with the risk of gallbladder cancer.

Food biodiversity and total and cause-specific mortality in 9 European countries: An analysis of a prospective cohort study.

BACKGROUND: Food biodiversity, encompassing the variety of plants, animals, and other organisms consumed as food and drink, has intrinsic potential to underpin diverse, nutritious diets and improve Earth system resilience. Dietary species richness (DSR), which is recommended as a crosscutting measure of food biodiversity, has been positively associated with the micronutrient adequacy of diets in women and young children in low- and middle-income countries (LMICs). However, the relationships between DSR and major health outcomes have yet to be assessed in any population. METHODS AND FINDINGS: We examined the associations between DSR and subsequent total and cause-specific mortality among 451,390 adults enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study (1992 to 2014, median follow-up: 17 years), free of cancer, diabetes, heart attack, or stroke at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires (DQs). DSR of an individual's yearly diet was calculated based on the absolute number of unique biological species in each (composite) food and drink. Associations were assessed by fitting multivariable-adjusted Cox proportional hazards regression models. In the EPIC cohort, 2 crops (common wheat and potato) and 2 animal species (cow and pig) accounted for approximately 45% of self-reported total dietary energy intake [median (P10-P90): 68 (40 to 83) species consumed per year]. Overall, higher DSR was inversely associated with all-cause mortality rate. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing total mortality in the second, third, fourth, and fifth (highest) quintiles (Qs) of DSR to the first (lowest) Q indicate significant inverse associations, after stratification by sex, age, and study center and adjustment for smoking status, educational level, marital status, physical activity, alcohol intake, and total energy intake, Mediterranean diet score, red and processed meat intake, and fiber intake [HR (95% CI): 0.91 (0.88 to 0.94), 0.80 (0.76 to 0.83), 0.69 (0.66 to 0.72), and 0.63 (0.59 to 0.66), respectively; PWald < 0.001 for trend]. Absolute death rates among participants in the highest and lowest fifth of DSR were 65.4 and 69.3 cases/10,000 person-years, respectively. Significant inverse associations were also observed between DSR and deaths due to cancer, heart disease, digestive disease, and respiratory disease. An important study limitation is that our findings were based on an observational cohort using self-reported dietary data obtained through single baseline food frequency questionnaires (FFQs); thus, exposure misclassification and residual confounding cannot be ruled out. CONCLUSIONS: In this large Pan-European cohort, higher DSR was inversely associated with total and cause-specific mortality, independent of sociodemographic, lifestyle, and other known dietary risk factors. Our findings support the potential of food (species) biodiversity as a guiding principle of sustainable dietary recommendations and food-based dietary guidelines.

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

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