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Dietary exposure to nitrites and nitrates in association with type 2 diabetes risk: Results from the NutriNet-Santé population-based cohort study.
Srour, B, Chazelas, E, Druesne-Pecollo, N, Esseddik, Y, de Edelenyi, FS, Agaësse, C, De Sa, A, Lutchia, R, Debras, C, Sellem, L, et al
PLoS medicine. 2023;(1):e1004149
Abstract
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).
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Soft Drink and Juice Consumption and Renal Cell Carcinoma Incidence and Mortality in the European Prospective Investigation into Cancer and Nutrition.
Heath, AK, Clasen, JL, Jayanth, NP, Jenab, M, Tjønneland, A, Petersen, KEN, Overvad, K, Srour, B, Katzke, V, Bergmann, MM, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2021;(6):1270-1274
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BACKGROUND Renal cell carcinoma (RCC) accounts for more than 80% of kidney cancers in adults, and obesity is a known risk factor. Regular consumption of sweetened beverages has been linked to obesity and several chronic diseases, including some types of cancer. It is uncertain whether soft drink and juice consumption is associated with risk of RCC. We investigated the associations of soft drink and juice consumption with RCC incidence and mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS A total of 389,220 EPIC participants with median age of 52 years at recruitment (1991-2000) were included. Cox regression yielded adjusted HRs and 95% confidence intervals (CI) for RCC incidence and mortality in relation to intakes of juices and total, sugar-sweetened, and artificially sweetened soft drinks. RESULTS A total of 888 incident RCCs and 356 RCC deaths were identified. In models including adjustment for body mass index and energy intake, there was no higher risk of incident RCC associated with consumption of juices (HR per 100 g/day increment = 1.03; 95% CI, 0.97-1.09), total soft drinks (HR = 1.01; 95% CI, 0.98-1.05), sugar-sweetened soft drinks (HR = 0.99; 95% CI, 0.94-1.05), or artificially sweetened soft drinks (HR = 1.02; 95% CI, 0.96-1.08). In these fully adjusted models, none of the beverages was associated with RCC mortality (HR, 95% CI per 100 g/day increment 1.06, 0.97-1.16; 1.03, 0.98-1.09; 0.97, 0.89-1.07; and 1.06, 0.99-1.14, respectively). CONCLUSIONS Consumption of juices or soft drinks was not associated with RCC incidence or mortality after adjusting for obesity. IMPACT Soft drink and juice intakes are unlikely to play an independent role in RCC development or mortality.
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Dietary Patterns, Ultra-processed Food, and the Risk of Inflammatory Bowel Diseases in the NutriNet-Santé Cohort.
Vasseur, P, Dugelay, E, Benamouzig, R, Savoye, G, Lan, A, Srour, B, Hercberg, S, Touvier, M, Hugot, JP, Julia, C, et al
Inflammatory bowel diseases. 2021;(1):65-73
Abstract
BACKGROUND The incidence of inflammatory bowel diseases (IBDs) tended to increase for several decades. Diet is suspected to be a major determinant of the occurrence of these diseases. This prospective study aimed to assess the associations among occurrence of IBD, dietary patterns, and ultra-processed food in the French NutriNet-Santé cohort. METHODS Participants of the NutriNet-Santé cohort who completed at least three 24-hour dietary records were included. Incident IBD cases were identified from 3 questionnaires and confirmed by phone or email interview. Major dietary patterns (DPs) were computed using a principal component analysis (PCA) based on 29 food groups' consumption, whereas proportions of ultra-processed foods (UPFs) were obtained using the NOVA classification. Multivariable Poisson models were performed to evaluate associations among DP quintiles, UPF proportion (UPFp) in the diet, and incident IBD. RESULTS A total of 105,832 participants were included, contributing 238,924 person-years in a mean follow-up of 2.3 ± 2.2 years. Among them, 75 participants reported an incident IBD. Three major DPs were retained: "healthy," "traditional," and "western." No significant association was found for DPs and UPFp after adjustments for covariates. CONCLUSIONS In this study, neither DPs nor UPF proportion in the diet were significantly associated with the risk of incident IBD after adjustments for covariates. Further studies are needed to investigate the long-term association between diet and IBD.
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Ultraprocessed Food Consumption and Risk of Type 2 Diabetes Among Participants of the NutriNet-Santé Prospective Cohort.
Srour, B, Fezeu, LK, Kesse-Guyot, E, Allès, B, Debras, C, Druesne-Pecollo, N, Chazelas, E, Deschasaux, M, Hercberg, S, Galan, P, et al
JAMA internal medicine. 2020;(2):283-291
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IMPORTANCE Ultraprocessed foods (UPF) are widespread in Western diets. Their consumption has been associated in recent prospective studies with increased risks of all-cause mortality and chronic diseases such as cancer, cardiovascular diseases, hypertension, and dyslipidemia; however, data regarding diabetes are lacking. OBJECTIVE To assess the associations between consumption of UPF and risk of type 2 diabetes (T2D). DESIGN, SETTING, AND PARTICIPANTS In this population-based prospective cohort study, 104 707 participants aged 18 years or older from the French NutriNet-Santé cohort (2009-2019) were included. Dietary intake data were collected using repeated 24-hour dietary records (5.7 per participant on average), designed to register participants' usual consumption for more than 3500 different food items. These were categorized according to their degree of processing by the NOVA classification system. MAIN OUTCOMES AND MEASURES Associations between UPF consumption 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). RESULTS A total of 104 707 participants (21 800 [20.8%] men and 82 907 [79.2%] women) were included. Mean (SD) baseline age of participants was 42.7 (14.5) years. Absolute T2D rates in the lowest and highest UPF consumers were 113 and 166 per 100 000 person-years, respectively. Consumption of UPF was associated with a higher risk of T2D (multi-adjusted hazard ratio [HR] for an absolute increment of 10 in the percentage of UPF in the diet, 1.15; 95% CI, 1.06-1.25; median follow-up, 6.0 years; 582 252 person-years; 821 incident cases). These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet, for other metabolic comorbidities (HR, 1.13; 95% CI, 1.03-1.23), and for weight change (HR, 1.13; 95% CI, 1.01-1.27). The absolute amount of UPF consumption (grams per day) was consistently associated with T2D risk, even when adjusting for unprocessed or minimally processed food intake (HR for a 100 g/d increase, 1.05; 95% CI, 1.02-1.08). CONCLUSIONS AND RELEVANCE In this large observational prospective study, a higher proportion of UPF in the diet was associated with a higher risk of T2D. Even though these results need to be confirmed in other populations and settings, they provide evidence to support efforts by public health authorities to recommend limiting UPF consumption. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03335644.
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Sugary drink consumption and risk of cancer: results from NutriNet-Santé prospective cohort.
Chazelas, E, Srour, B, Desmetz, E, Kesse-Guyot, E, Julia, C, Deschamps, V, Druesne-Pecollo, N, Galan, P, Hercberg, S, Latino-Martel, P, et al
BMJ (Clinical research ed.). 2019;:l2408
Abstract
OBJECTIVE To assess the associations between the consumption of sugary drinks (such as sugar sweetened beverages and 100% fruit juices), artificially sweetened beverages, and the risk of cancer. DESIGN Population based prospective cohort study. SETTING AND PARTICIPANTS Overall, 101 257 participants aged 18 and over (mean age 42.2, SD 14.4; median follow-up time 5.1 years) from the French NutriNet-Santé cohort (2009-2017) were included. Consumptions of sugary drinks and artificially sweetened beverages were assessed by using repeated 24 hour dietary records, which were designed to register participants' usual consumption for 3300 different food and beverage items. MAIN OUTCOME MEASURES Prospective associations between beverage consumption and the risk of overall, breast, prostate, and colorectal cancer were assessed by multi-adjusted Fine and Gray hazard models, accounting for competing risks. Subdistribution hazard ratios were computed. RESULTS The consumption of sugary drinks was significantly associated with the risk of overall cancer (n=2193 cases, subdistribution hazard ratio for a 100mL/d increase 1.18, 95% confidence interval 1.10 to 1.27, P<0.0001) and breast cancer (693, 1.22, 1.07 to 1.39, P=0.004). The consumption of artificially sweetened beverages was not associated with the risk of cancer. In specific subanalyses, the consumption of 100% fruit juice was significantly associated with the risk of overall cancer (2193, 1.12, 1.03 to 1.23, P=0.007). CONCLUSIONS In this large prospective study, the consumption of sugary drinks was positively associated with the risk of overall cancer and breast cancer. 100% fruit juices were also positively associated with the risk of overall cancer. These results need replication in other large scale prospective studies. They suggest that sugary drinks, which are widely consumed in Western countries, might represent a modifiable risk factor for cancer prevention. STUDY REGISTRATION ClinicalTrials.gov NCT03335644.
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Association Between Ultraprocessed Food Consumption and Risk of Mortality Among Middle-aged Adults in France.
Schnabel, L, Kesse-Guyot, E, Allès, B, Touvier, M, Srour, B, Hercberg, S, Buscail, C, Julia, C
JAMA internal medicine. 2019;(4):490-498
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IMPORTANCE Growing evidence indicates that higher intake of ultraprocessed foods is associated with higher incidence of noncommunicable diseases. However, to date, the association between ultraprocessed foods consumption and mortality risk has never been investigated. OBJECTIVE To assess the association between ultraprocessed foods consumption and all-cause mortality risk. DESIGN, SETTING, AND PARTICIPANTS This observational prospective cohort study selected adults, 45 years or older, from the French NutriNet-Santé Study, an ongoing cohort study that launched on May 11, 2009, and performed a follow-up through December 15, 2017 (a median of 7.1 years). Participants were selected if they completed at least 1 set of 3 web-based 24-hour dietary records during their first 2 years of follow-up. Self-reported data were collected at baseline, including sociodemographic, lifestyle, physical activity, weight and height, and anthropometrics. EXPOSURES The ultraprocessed foods group (from the NOVA food classification system), characterized as ready-to-eat or -heat formulations made mostly from ingredients usually combined with additives. Proportion (in weight) of ultraprocessed foods in the diet was computed for each participant. MAIN OUTCOMES AND MEASURES The association between proportion of ultraprocessed foods and overall mortality was the main outcome. Mean dietary intakes from all of the 24-hour dietary records available during the first 2 years of follow-up were calculated and considered as the baseline usual food-and-drink intakes. Mortality was assessed using CépiDC, the French national registry of specific mortality causes. Hazard ratios (HRs) and 95% CIs were determined for all-cause mortality, using multivariable Cox proportional hazards regression models, with age as the underlying time metric. RESULTS A total of 44 551 participants were included, of whom 32 549 (73.1%) were women, with a mean (SD) age at baseline of 56.7 (7.5) years. Ultraprocessed foods accounted for a mean (SD) proportion of 14.4% (7.6%) of the weight of total food consumed, corresponding to a mean (SD) proportion of 29.1% (10.9%) of total energy intake. Ultraprocessed foods consumption was associated with younger age (45-64 years, mean [SE] proportion of food in weight, 14.50% [0.04%]; P < .001), lower income (<€1200/mo, 15.58% [0.11%]; P < .001), lower educational level (no diploma or primary school, 15.50% [0.16%]; P < .001), living alone (15.02% [0.07%]; P < .001), higher body mass index (calculated as weight in kilograms divided by height in meters squared; ≥30, 15.98% [0.11%]; P < .001), and lower physical activity level (15.56% [0.08%]; P < .001). A total of 602 deaths (1.4%) occurred during follow-up. After adjustment for a range of confounding factors, an increase in the proportion of ultraprocessed foods consumed was associated with a higher risk of all-cause mortality (HR per 10% increment, 1.14; 95% CI, 1.04-1.27; P = .008). CONCLUSIONS AND RELEVANCE An increase in ultraprocessed foods consumption appears to be associated with an overall higher mortality risk among this adult population; further prospective studies are needed to confirm these findings and to disentangle the various mechanisms by which ultraprocessed foods may affect health.
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Ultra-processed food intake and risk of cardiovascular disease: prospective cohort study (NutriNet-Santé).
Srour, B, Fezeu, LK, Kesse-Guyot, E, Allès, B, Méjean, C, Andrianasolo, RM, Chazelas, E, Deschasaux, M, Hercberg, S, Galan, P, et al
BMJ (Clinical research ed.). 2019;:l1451
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OBJECTIVE To assess the prospective associations between consumption of ultra-processed foods and risk of cardiovascular diseases. DESIGN Population based cohort study. SETTING NutriNet-Santé cohort, France 2009-18. PARTICIPANTS 105 159 participants aged at least 18 years. Dietary intakes were collected using repeated 24 hour dietary records (5.7 for each participant on average), designed to register participants' usual consumption of 3300 food items. These foods were categorised using the NOVA classification according to degree of processing. MAIN OUTCOME MEASURES Associations between intake of ultra-processed food and overall risk of cardiovascular, coronary heart, and cerebrovascular diseases assessed by multivariable Cox proportional hazard models adjusted for known risk factors. RESULTS During a median follow-up of 5.2 years, intake of ultra-processed food was associated with a higher risk of overall cardiovascular disease (1409 cases; hazard ratio for an absolute increment of 10 in the percentage of ultra-processed foods in the diet 1.12 (95% confidence interval 1.05 to 1.20); P<0.001, 518 208 person years, incidence rates in high consumers of ultra-processed foods (fourth quarter) 277 per 100 000 person years, and in low consumers (first quarter) 242 per 100 000 person years), coronary heart disease risk (665 cases; hazard ratio 1.13 (1.02 to 1.24); P=0.02, 520 319 person years, incidence rates 124 and 109 per 100 000 person years, in the high and low consumers, respectively), and cerebrovascular disease risk (829 cases; hazard ratio 1.11 (1.01 to 1.21); P=0.02, 520 023 person years, incidence rates 163 and 144 per 100 000 person years, in high and low consumers, respectively). These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet (saturated fatty acids, sodium and sugar intakes, dietary fibre, or a healthy dietary pattern derived by principal component analysis) and after a large range of sensitivity analyses. CONCLUSIONS In this large observational prospective study, higher consumption of ultra-processed foods was associated with higher risks of cardiovascular, coronary heart, and cerebrovascular diseases. These results need to be confirmed in other populations and settings, and causality remains to be established. Various factors in processing, such as nutritional composition of the final product, additives, contact materials, and neoformed contaminants might play a role in these associations, and further studies are needed to understand better the relative contributions. Meanwhile, public health authorities in several countries have recently started to promote unprocessed or minimally processed foods and to recommend limiting the consumption of ultra-processed foods. STUDY REGISTRATION ClinicalTrials.gov NCT03335644.
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Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study.
Deschasaux, M, Huybrechts, I, Murphy, N, Julia, C, Hercberg, S, Srour, B, Kesse-Guyot, E, Latino-Martel, P, Biessy, C, Casagrande, C, et al
PLoS medicine. 2018;(9):e1002651
Abstract
BACKGROUND Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations. METHODS AND FINDINGS This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus Q1 = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out. CONCLUSIONS In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.
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Variations of physical activity and sedentary behavior between before and after cancer diagnosis: Results from the prospective population-based NutriNet-Santé cohort.
Fassier, P, Zelek, L, Partula, V, Srour, B, Bachmann, P, Touillaud, M, Druesne-Pecollo, N, Galan, P, Cohen, P, Hoarau, H, et al
Medicine. 2016;(40):e4629
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Physical activity (PA) but also reduced sedentary behavior may be associated with better prognosis and lower risk of recurrence in cancer patients. Our aim was to quantify the variations in PA and time spent sedentary between before and after diagnosis, relying on prospective data in French adults. We also investigated sociodemographic and lifestyle factors associated with these variations.Subjects (n = 942) were incident cancer cases diagnosed in the NutriNet-Santé cohort between 2009 and 2015. PA and sedentary behavior were prospectively collected with the 7-day short version of the IPAQ questionnaire every year since subjects' inclusion (i.e., an average of 2 year before diagnosis). All PA and sitting time points before and after diagnosis was compared by mixed model. Factors associated with decrease in PA and increase in sitting time were investigated using logistic regressions.Overall and vigorous PA decreased after diagnosis (P = 0.006, -32.8 ± 36.8 MET-hour/week on average, in those who decreased their overall PA and P = 0.005, -21.1 ± 36.8 MET-hour/week for vigorous PA, respectively), especially in prostate (-39.5 ± 36.3 MET-hour/week) and skin (-35.9 ± 38 MET-hour/week) cancers, in men (-40.8 ± 46.3MET-hour/week), and in those professionally inactive (-34.2 ± 37.1 MET-hour/week) (all P < 0.05). Patients with higher PA level before diagnosis were more likely to decrease their PA (odds ratio [OR]: 4.67 [3.21-6.81], P < 0.0001). Overweight patients more likely to decrease moderate PA (OR: 1.45 [1.11-1.89], P = 0.006) and walking (OR: 1.30 [1.10-1.70], P = 0.04). Sitting time increased (P = 0.02, +2.44 ± 2.43 hour/day on average, in those who increased their sitting time), especially in women (+2.48 ± 2.48 hour/day), older patients (+2.48 ± 2.57 hour/day), and those professionally inactive (2.41 ± 2.40 hour/day) (all P < 0.05). Patients less sedentary before diagnosis were more likely to increase their sitting time (OR: 3.29 [2.45-4.42], P < 0.0001).This large prospective study suggests that cancer diagnosis is a key period for change in PA and sedentary behavior. It provides insights to target the subgroups of patients who are at higher risk of decreasing PA and increasing sedentary behavior after cancer diagnosis.