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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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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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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
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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.
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International evidence for the effectiveness of the front-of-package nutrition label called Nutri-Score.
Andreeva, VA, Egnell, M, Touvier, M, Galan, P, Julia, C, Hercberg, S
Central European journal of public health. 2021;(1):76-79
Abstract
OBJECTIVES Front-of-package nutrition labels are intended to easily convey to consumers comprehensible information about the nutritional composition of pre-packaged food and are thus a tool in the combat against the growing prevalence of nutrition-related disorders, such as obesity, type 2 diabetes, cardiovascular disease, and some types of cancer. The objective of the present narrative review was first to describe Nutri-Score and then to synthesize some of the international scientific evidence for its effectiveness. Guided by scientific data and collective expertise, France formally adopted labelling of pre-packaged food with the 5-colour Nutri-Score label in October 2017 and that move was later followed by Belgium, Spain, Germany, Switzerland, the Netherlands, and Luxembourg. METHODS This article synthesizes evidence from several countries regarding the effectiveness of Nutri-Score and the associated individual-level diet quality index in terms of attitude/behaviour- and health-related outcomes. It also addresses criticism levied at the label. RESULTS The effectiveness of Nutri-Score has been demonstrated in terms of consumer ability to correctly classify food according to its nutritional quality, the nutritional quality of actual and intended food purchases, and portion size choices. In addition, consumption of foods that are less favourably rated on the Nutri-Score scale has been prospectively associated with chronic disease risk (cancer, cardiovascular disease, metabolic syndrome, etc.). CONCLUSION The adoption and implementation of a uniform front-of-package label such as the scientifically validated Nutri-Score on pre-packaged foods/beverages across Europe could be beneficial to consumers at the point of purchase and could help reduce the incidence of diet-related chronic diseases by means of improvement in diet quality.
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The impact of the Nutri-Score front-of-pack nutrition label on purchasing intentions of unprocessed and processed foods: post-hoc analyses from three randomized controlled trials.
Egnell, M, Galan, P, Fialon, M, Touvier, M, Péneau, S, Kesse-Guyot, E, Hercberg, S, Julia, C
The international journal of behavioral nutrition and physical activity. 2021;18(1):38
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Plain language summary
In order to prevent nutrition-related chronic diseases, Front-of-Pack nutrition Labels (FoPL) have been identified as efficient tools to encourage consumers towards healthier food choices and to promote food reformulation. The aim of this study was to investigate the impact of the Nutri-Score, compared to the current labelling situation in France (i.e., Reference Intakes (RIs) or no label), on food purchasing intentions. This study is a post-hoc analysis of three randomised controlled studies in three specific populations; students (N = 1866), low-income individuals (N = 336) and subjects suffering from cardiometabolic diseases (N = 1180). Results show that overall, participants (students, low-income individuals and subjects suffering from cardiometabolic diseases) simulating purchases with the Nutri-Score affixed on pre-packed foods were more likely to have higher proportions of unpacked products (especially unprocessed fruits and meat) in their shopping cart. Furthermore, Nutri-Score influenced the type of food purchased; less ultra-processed foods which have been found to be often of lower nutritional quality. Authors conclude that Nutri-Score may have a positive impact on food purchases which would discourage the purchase of pre-packed processed products.
Abstract
BACKGROUND The Nutri-Score summary graded front-of-pack nutrition label has been identified as an efficient tool to increase the nutritional quality of pre-packed food purchases. However, no study has been conducted to investigate the effect of the Nutri-Score on the shopping cart composition, considering the type of foods. The present paper aims to investigate the effect of the Nutri-Score on the type of food purchases, in terms of the relative contribution of unpacked and pre-packed foods, or the processing degree of foods. METHODS Between September 2016 and April 2017, three consecutive randomized controlled trials were conducted in three specific populations - students (N = 1866), low-income individuals (N = 336) and subjects suffering from cardiometabolic diseases (N = 1180) - to investigate the effect of the Nutri-Score on purchasing intentions compared to the Reference Intakes and no label. Using these combined data, the proportion of unpacked products in the shopping carts, as well as the distribution of products across food categories taking into account the degree of processing (NOVA classification) were assessed by trials arm. RESULTS The shopping carts of participants simulating purchases with the Nutri-Score affixed on pre-packed foods contained higher proportion of unpacked products - especially raw fruits and meats, i.e. with no FoPL -, compared to participants purchasing with no label (difference of 5.93 percentage points [3.88-7.99], p-value< 0.0001) or with the Reference Intakes (difference of 5.27[3.25-7.29], p-value< 0.0001). This higher proportion was partly explained by fewer purchases of pre-packed processed and ultra-processed products overall in the Nutri-Score group. CONCLUSIONS These findings provide new insights on the positive effect of the Nutri-Score, which appears to decrease purchases in processed products resulting in higher proportions of unprocessed and unpacked foods, in line with public health recommendations.
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Organic food consumption and gluten-free diet, is there a link? Results in French adults without coeliac disease.
Perrin, L, Allès, B, Julia, C, Hercberg, S, Touvier, M, Lairon, D, Baudry, J, Kesse-Guyot, E
The British journal of nutrition. 2021;125(9):1067-1078
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The gluten-free diet (GFD) is a medical response for people with coeliac disease, a systemic autoimmune disorder for which GFD is the only available effective treatment. The aim of this study was to compare the consumption of organic products (as a whole and by food group) in individuals (partially or totally) avoiding gluten or not, and their places of food purchases of organic food. Results indicate a positive association between gluten avoidance and contribution of organic food to the diet. A gradient was also observed with total avoiders consuming more of organic food than partial avoiders. This contribution was higher for all types of products, except milk and dairy products. Furthermore, the results appear consistent with the motives reported by individuals avoiding gluten. Authors conclude that their findings underline a strong positive correlation between gluten avoidance and organic food consumption.
Abstract
The rising popular belief that gluten is unhealthy has led to growth in gluten avoidance in people without coeliac disease. Little information is available on their dietary profiles and their dietary behaviours. Our aim was to compare the consumption of organic foods between gluten avoiders and non-avoiders, and their places of food purchase. We described their sociodemographic and dietary profiles. The study population included participants of the NutriNet-Santé cohort who completed both a food exclusion questionnaire and an organic semi-quantitative FFQ (n 23 468). Food intake and organic food consumption ratios were compared using multivariable adjusted ANCOVA models. Associations between gluten avoidance and organic food consumption as well as places of food purchase were investigated with multivariable logistic regression. Participants avoiding gluten were more likely to be women and had a healthier dietary profile. Organic food consumption was higher among gluten avoiders (48·50 % of total diet for total avoiders, 17·38 % for non-avoiders). After adjustments for confounders, organic food consumption and purchase in organic stores were positively associated with gluten avoidance: adjusted OR (aOR)Q5 v.Q1 organic food = 4·95; 95 % CI 3·70, 6·63 and aORorganic stores v.supermarkets = 1·82; 95 % CI 1·42, 2·33 for total avoiders. Our study highlights that individuals avoiding gluten are high organic consumers and frequently purchase their foods in organic stores which propose an extended offer of gluten-free food. Further research is needed to determine the underlying common motivations and the temporality of the dietary behaviours of healthy people avoiding gluten.