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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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Ultra-processed food exposure and adverse health outcomes: umbrella review of epidemiological meta-analyses.
Lane, MM, Gamage, E, Du, S, Ashtree, DN, McGuinness, AJ, Gauci, S, Baker, P, Lawrence, M, Rebholz, CM, Srour, B, et al
BMJ (Clinical research ed.). 2024;:e077310
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Abstract
OBJECTIVE To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. DESIGN Systematic umbrella review of existing meta-analyses. DATA SOURCES MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manual searches of reference lists from 2009 to June 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Systematic reviews and meta-analyses of cohort, case-control, and/or cross sectional study designs. To evaluate the credibility of evidence, pre-specified evidence classification criteria were applied, graded as convincing ("class I"), highly suggestive ("class II"), suggestive ("class III"), weak ("class IV"), or no evidence ("class V"). The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework, categorised as "high," "moderate," "low," or "very low" quality. RESULTS The search identified 45 unique pooled analyses, including 13 dose-response associations and 32 non-dose-response associations (n=9 888 373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health parameters spanning mortality, cancer, and mental, respiratory, cardiovascular, gastrointestinal, and metabolic health outcomes. Based on the pre-specified evidence classification criteria, convincing evidence (class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease related mortality (risk ratio 1.50, 95% confidence interval 1.37 to 1.63; GRADE=very low) and type 2 diabetes (dose-response risk ratio 1.12, 1.11 to 1.13; moderate), as well as higher risks of prevalent anxiety outcomes (odds ratio 1.48, 1.37 to 1.59; low) and combined common mental disorder outcomes (odds ratio 1.53, 1.43 to 1.63; low). Highly suggestive (class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all cause mortality (risk ratio 1.21, 1.15 to 1.27; low), heart disease related mortality (hazard ratio 1.66, 1.51 to 1.84; low), type 2 diabetes (odds ratio 1.40, 1.23 to 1.59; very low), and depressive outcomes (hazard ratio 1.22, 1.16 to 1.28; low), together with higher risks of prevalent adverse sleep related outcomes (odds ratio 1.41, 1.24 to 1.61; low), wheezing (risk ratio 1.40, 1.27 to 1.55; low), and obesity (odds ratio 1.55, 1.36 to 1.77; low). Of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (class III-IV) and 13 were graded as no evidence (class V). Overall, using the GRADE framework, 22 pooled analyses were rated as low quality, with 19 rated as very low quality and four rated as moderate quality. CONCLUSIONS Greater exposure to ultra-processed food was associated with a higher risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to develop and evaluate the effectiveness of using population based and public health measures to target and reduce dietary exposure to ultra-processed foods for improved human health. They also inform and provide support for urgent mechanistic research. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42023412732.
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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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Trust in sources of information on COVID-19 at the beginning of the pandemic's first wave and incident persistent symptoms in the population-based CONSTANCES cohort: A prospective study.
Matta, J, Wiernik, E, Robineau, O, Severi, G, Touvier, M, Gouraud, C, Ouazana-Vedrines, C, Pitron, V, Ranque, B, Hoertel, N, et al
Journal of psychosomatic research. 2023;:111326
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OBJECTIVE To examine the association between trust in different sources of information on COVID-19 at the beginning of the pandemic and the burden of incident persistent symptoms. METHODS This prospective study used data from the SAPRIS and SAPRIS-Sérologie surveys nested in the French CONSTANCES population-based cohort. Trust in different information sources was measured between April 6 and May 4, 2020. Persistent symptoms that emerged afterwards were self-reported between December 2020 and January 2021. The associated psychological burden was measured with the somatic symptom disorder B criteria scale (SSD-12). The analyses were adjusted for gender, age, education, income, self-rated health, SARS-CoV-2 serology tests, and self-reported COVID-19. RESULTS Among 20,985 participants [mean age (SD), 49.0 years (12.7); 50.2% women], those with higher trust in government/journalists at baseline had fewer incident persistent symptoms at follow-up (estimate (SE) for one IQR increase: -0.21 (0.03), p < 0.001). Participants with higher trust in government/journalists and medical doctors/scientists were less likely to have ≥1 symptom (odds ratio (95% confidence interval) for one IQR increase: 0.87 (0.82-0.91) and 0.91 (0.85-0.98), respectively). Among 3372 participants (16.1%) who reported ≥1 symptom, higher trust in government/journalists and medical doctors/scientists predicted lower SSD-12 scores (-0.39 (0.17), p = 0.02 and - 0.85 (0.24), p < 0.001, respectively), whereas higher trust in social media predicted higher scores in those with lower trust in government/journalists (0.90 (0.34), p = 0.008). These associations did not depend upon surrogate markers of infection with SARS-CoV-2. CONCLUSIONS Trust in information sources on COVID-19 may be associated with incident persistent symptoms and associated psychological burden, regardless of infection with SARS-CoV-2.
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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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Ultra-processed foods and human health: from epidemiological evidence to mechanistic insights.
Srour, B, Kordahi, MC, Bonazzi, E, Deschasaux-Tanguy, M, Touvier, M, Chassaing, B
The lancet. Gastroenterology & hepatology. 2022;(12):1128-1140
Abstract
Epidemiological studies have suggested a role for ultra-processed foods in numerous chronic inflammatory diseases such as inflammatory bowel diseases and metabolic syndrome. Preclinical and clinical studies are accumulating to better decipher the effects of various aspects of food processing and formulation on the aetiology of chronic, debilitating inflammatory diseases. In this Review, we provide an overview of the current data that highlight an association between ultra-processed food consumption and various chronic diseases, with a focus on epidemiological evidence and mechanistic insights involving the intestinal microbiota.
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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.