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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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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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Dietary pesticide exposure and non-communicable diseases and mortality: a systematic review of prospective studies among adults.
Baudry, J, Rebouillat, P, Samieri, C, Berlivet, J, Kesse-Guyot, E
Environmental health : a global access science source. 2023;(1):76
Abstract
BACKGROUND Research on the effect of pesticide exposure on health has been largely focused on occupational settings. Few reviews have synthesized the associations between dietary pesticide exposure and health outcomes in non-occupationally exposed adults. OBJECTIVE We aim to summarize the evidence regarding dietary pesticide exposure and non-communicable diseases (NCD) in adults, using a systematic review of prospective studies. METHODS Electronic and manual searches were performed until July 2023. The inclusion criteria were the following: 1) adults aged ≥ 18years, 2) (non)-randomized trials, prospective cohort studies, 3) dietary exposure to pesticides. A bias analysis was carried out using the Nutrition Evidence Systematic Review guidelines based on the Cochrane ROBINS-I. RESULTS A total of 52 studies were retrieved and 6 studies that met the above criteria were included. Studies were conducted either in France or in the United States. The studies investigated the risk of cancer (n = 3), diabetes (n = 1), cardiovascular diseases (n = 1), and mortality (n = 1). The quality of the studies varied with overall grades derived from the bias analysis ranging from low to moderate bias. The level of evidence was estimated as low for the risk of cancer while the grading was not assignable for other outcomes, as only one study per outcome was available. CONCLUSIONS Although further research is warranted to examine more in depth the relationships between low-dose chronic exposure to pesticides through diet and NCD outcomes in non-occupationally-exposed adults, studies suggest a possible role of exposure to dietary pesticide on health. Standardized methodological guidelines should also be proposed to allow for comparison across studies.
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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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Abstract
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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Impact of the Nutri-Score front-of-pack nutrition label on purchasing intentions of individuals with chronic diseases: results of a randomised trial.
Egnell, M, Boutron, I, Péneau, S, Ducrot, P, Touvier, M, Galan, P, Fezeu, L, Porcher, R, Ravaud, P, Hercberg, S, et al
BMJ open. 2022;(8):e058139
Abstract
OBJECTIVE To our knowledge, the effect of front-of-pack nutrition labels such as the Nutri-Score on food purchases has never been assessed among individuals suffering from nutrition-related chronic diseases specifically, while dietary modifications are generally part of their care. This study aimed to investigate the effect of the Nutri-Score on the nutritional quality of purchasing intentions among adults suffering from a cardiometabolic disease, compared with no label and the Reference Intakes (RIs), a label already implemented by some food manufacturers in France. SETTING Secondary prevention-mainland France. PARTICIPANTS 2431 eligible participants were randomly assigned and 1180 participants (65.5% women, mean age 65.0±7.1 years) completed the shopping task and were included in the analyses. INTERVENTION A three-arm randomised controlled trial using an experimental online supermarket was conducted in 2017. Participants with cardiometabolic diseases were invited to simulate food purchases with the Nutri-Score, the RIs or no label. PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome was the nutritional quality of the shopping cart, estimated using the French-modified Food Standard Agency Nutrient Profiling System (FSAm-NPS), and secondary outcomes included the nutrient content of purchases. RESULTS The mean (SD) FSAm-NPS score was significantly lower in the Nutri-Score arm (1.29 (3.61) points), reflecting a higher overall nutritional quality of purchasing intentions, compared with the RIs (1.86 (3.23) points) and no label (1.92 (2.90) points) arms (p=0.01). Moreover, the Nutri-Score led to significantly lower content in calories and saturated fatty acids compared with the two other arms. These differences resulted from participants avoiding some packaged products (sweets, dairy and starches) and purchasing larger amounts of fresh fruit and meat. CONCLUSIONS The Nutri-Score exhibited a significant higher nutritional quality of purchasing intentions, encouraging healthier food choices among individuals suffering from cardiometabolic chronic diseases. TRIAL REGISTRATION NUMBER NCT02769455.
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Ultra-processed foods and cancer risk: from global food systems to individual exposures and mechanisms.
Kliemann, N, Al Nahas, A, Vamos, EP, Touvier, M, Kesse-Guyot, E, Gunter, MJ, Millett, C, Huybrechts, I
British journal of cancer. 2022;(1):14-20
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Abstract
Ultra-processed foods (UPFs) have become increasingly dominant globally, contributing to as much as 60% of total daily energy intake in some settings. Epidemiological evidence suggests this worldwide shift in food processing may partly be responsible for the global obesity epidemic and chronic disease burden. However, prospective studies examining the association between UPF consumption and cancer outcomes are limited. Available evidence suggests that UPFs may increase cancer risk via their obesogenic properties as well as through exposure to potentially carcinogenic compounds such as certain food additives and neoformed processing contaminants. We identify priority areas for future research and policy implications, including improved understanding of the potential dual harms of UPFs on the environment and cancer risk. The prevention of cancers related to the consumption of UPFs could be tackled using different strategies, including behaviour change interventions among consumers as well as bolder public health policies needed to improve food environments.
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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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Comment on Muzzioli et al. Are Front-of-Pack Labels a Health Policy Tool? Nutrients 2022, 14, 771.
Aguenaou, H, Babio, N, Deschasaux-Tanguy, M, Galan, P, Hercberg, S, Julia, C, Jones, A, Karpetas, G, Kelly, B, Kesse-Guyot, E, et al
Nutrients. 2022;(10)
Abstract
As scientists working and publishing in the field of front-of-pack nutrition labelling (FOPNL) for many years, we have read with interest and concern the narrative review regarding their effectiveness by Muzzioli et al. [...].
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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
Abstract
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.