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Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohort.
Sellem, L, Srour, B, Javaux, G, Chazelas, E, Chassaing, B, Viennois, E, Debras, C, Druesne-Pecollo, N, Esseddik, Y, Szabo de Edelenyi, F, et al
PLoS medicine. 2024;(2):e1004338
Abstract
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.
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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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ABO blood types and SARS-CoV-2 infection assessed using seroprevalence data in a large population-based sample: the SAPRIS-SERO multi-cohort study.
Deschasaux-Tanguy, M, Szabo de Edelenyi, F, Druesne-Pecollo, N, Esseddik, Y, Allègre, J, Srour, B, Galan, P, Hercberg, S, Severi, G, Zins, M, et al
Scientific reports. 2023;(1):4775
Abstract
ABO blood type has been reported as a potential factor influencing SARS-CoV-2 infection, but so far mostly in studies that involved small samples, selected population and/or used PCR test results. In contrast our study aimed to assess the association between ABO blood types and SARS-CoV-2 infection using seroprevalence data (independent of whether or not individuals had symptoms or sought for testing) in a large population-based sample. Our study included 67,340 French participants to the SAPRIS-SERO multi-cohort project. Anti-SARS-CoV-2 antibodies were detected using ELISA (targeting the proteins spike (S) and nucleocapsid (NP)) and seroneutralisation (SN) tests on dried blood spots collected in May-November 2020. Non-O individuals (and especially types A and AB) were more likely to bear anti SARS-CoV-2 antibodies (ELISA-S, 2964 positive cases: ORnon-Ovs.O = 1.09[1.01-1.17], ORAvs.O = 1.08[1.00-1.17]; ELISA-S/ELISA-NP/SN, 678 triple positive cases: ORnon-Ovs.O = 1.19 [1.02-1.39], ORAvs.O = 1.19[1.01-1.41], ORABvs.O = 1.43[1.01-2.03]). Hence, our results provided additional insights into the dynamic of SARS-CoV-2 infection, highlighting a higher susceptibility of infection for individuals of blood types A and AB and a lesser risk for blood type O.
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Dietary circadian rhythms and cardiovascular disease risk in the prospective NutriNet-Santé cohort.
Palomar-Cros, A, Andreeva, VA, Fezeu, LK, Julia, C, Bellicha, A, Kesse-Guyot, E, Hercberg, S, Romaguera, D, Kogevinas, M, Touvier, M, et al
Nature communications. 2023;(1):7899
Abstract
Daily eating/fasting cycles synchronise circadian peripheral clocks, involved in the regulation of the cardiovascular system. However, the associations of daily meal and fasting timing with cardiovascular disease (CVD) incidence remain unclear. We used data from 103,389 adults in the NutriNet-Santé study. Meal timing and number of eating occasions were estimated from repeated 24 h dietary records. We built multivariable Cox proportional-hazards models to examine their association with the risk of CVD, coronary heart disease and cerebrovascular disease. In this study, having a later first meal (later than 9AM compared to earlier than 8AM) and last meal of the day (later than 9PM compared to earlier than 8PM) was associated with a higher risk of cardiovascular outcomes, especially among women. Our results suggest a potential benefit of adopting earlier eating timing patterns, and coupling a longer nighttime fasting period with an early last meal, rather than breakfast skipping, in CVD prevention.
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Key Findings of the French BioNutriNet Project on Organic Food-Based Diets: Description, Determinants, and Relationships to Health and the Environment.
Kesse-Guyot, E, Lairon, D, Allès, B, Seconda, L, Rebouillat, P, Brunin, J, Vidal, R, Taupier-Letage, B, Galan, P, Amiot, MJ, et al
Advances in nutrition (Bethesda, Md.). 2022;(1):208-224
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Abstract
Few studies have investigated the relationships between organic food consumption, dietary patterns, monetary diet cost, health, and the environment. To address these issues, a consortium of French epidemiologists, nutritionists, economists, and toxicologists launched the BioNutriNet project in 2013. In 2014, an FFQ documented the usual organic and nonorganic (conventional) food consumption of approximately 35,000 NutriNet-Santé participants. Then, individual organic and conventional food intakes were merged with price, environmental, and pesticide residue data sets, which distinguished between conventional and organic farming methods. Many studies were conducted to characterize organic consumers and their environmental impacts (i.e., greenhouse gas emissions, energy demand, and land use) and organic food consumption impacts on health. We observed that organic consumers had diets that were healthier and richer in plant-based food than nonorganic consumers. Their diets were associated with higher monetary costs, lower environmental impacts, and reduced exposure to certain pesticide residues. Regular consumption of organic food was associated with reduced risks of obesity, type 2 diabetes, postmenopausal breast cancer, and lymphoma. Although several observations have been confirmed by several studies conducted in other countries, our results should be replicated in other cultural settings and coupled with experimental studies to be able to draw causal conclusions. Finally, the main finding of the BioNutriNet project is that while organic food consumption could be associated with positive externalities on human health and the environment, organic-based diets should be accompanied by dietary shifts toward plant-based diets to allow for better planetary and human health.
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Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study.
Debras, C, Chazelas, E, Srour, B, Druesne-Pecollo, N, Esseddik, Y, Szabo de Edelenyi, F, Agaësse, C, De Sa, A, Lutchia, R, Gigandet, S, et al
PLoS medicine. 2022;(3):e1003950
Abstract
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.
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Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAPs) and Cancer Risk in the Prospective NutriNet-Santé Cohort.
Debras, C, Chazelas, E, Srour, B, Julia, C, Schneider, É, Kesse-Guyot, E, Agaësse, C, Druesne-Pecollo, N, Andreeva, VA, Wendeu-Foyet, G, et al
The Journal of nutrition. 2022;(4):1059-1069
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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.
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Microbiome and metabolome features of the cardiometabolic disease spectrum.
Fromentin, S, Forslund, SK, Chechi, K, Aron-Wisnewsky, J, Chakaroun, R, Nielsen, T, Tremaroli, V, Ji, B, Prifti, E, Myridakis, A, et al
Nature medicine. 2022;(2):303-314
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Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages-acute coronary syndrome, chronic IHD and IHD with heart failure-and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.
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Association between adherence to the EAT-Lancet diet and risk of cancer and cardiovascular outcomes in the prospective NutriNet-Santé cohort.
Berthy, F, Brunin, J, Allès, B, Fezeu, LK, Touvier, M, Hercberg, S, Galan, P, Pointereau, P, Lairon, D, Baudry, J, et al
The American journal of clinical nutrition. 2022;(4):980-991
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BACKGROUND The EAT-Lancet commission proposed, in 2019, a planetary, healthy, and universal dietary pattern. However, this diet has rarely been studied in relation to various health outcomes. OBJECTIVES We aimed to prospectively estimate the association between the EAT-Lancet diet and cancer and cardiovascular disease (CVD) risk. METHODS The study was conducted in participants of the NutriNet-Santé cohort (2009-2021). The endpoints were the incident outcomes (cancer and CVDs and mortality from these diseases), combined and separately. Adherence to the EAT-Lancet diet was estimated using the EAT-Lancet Diet Index (ELD-I) modeled as quintiles (Qs). Multivariable Cox proportional hazard models were used to estimate HRs and 95% CIs, adjusted for potential confounders and moderators. RESULTS A total of 62,382 subjects were included; 2475 cases of cancer and 786 cases of cardiovascular events occurred during a median follow-up of 8.1 y. The sample was 76% female, the mean ± SD age at inclusion was 51.0 ± 10.2 y. The ELD-I ranged from -162 to 332 points with a mean ± SD score of 45.4 ± 25.6 points. In multivariable models, no significant association between the EAT-Lancet diet and the risk of cancer and CVD combined, and separately, was observed. Alcohol consumption was an effect modifier of the association. A significant association was observed among low drinkers (HRQ5vs.Q1: 0.86; 95% CI: 0.73, 1.02; P-trend = 0.02). A higher ELD-I was significantly associated with a lower risk of overall cancer only among females (HRQ5vs.Q1: 0.89; 95% CI: 0.75, 1.05; P-trend = 0.03). Both associations were largely attenuated by BMI. CONCLUSIONS Contrary to our hypothesis, our results documented significant associations between adherence to the EAT-Lancet diet and incidence of cancer only in some subgroups, and no association with CVD.This trial was registered at clinicaltrials.gov as NCT03335644.
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Nitrites, Nitrates, and Cardiovascular Outcomes: Are We Living "La Vie en Rose" With Pink Processed Meats?
Srour, B, Chazelas, E, Fezeu, LK, Javaux, G, Pierre, F, Huybrechts, I, Hercberg, S, Deschasaux-Tanguy, M, Kesse-Guyot, E, Touvier, M
Journal of the American Heart Association. 2022;(24):e027627
Abstract
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.