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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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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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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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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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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.
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Prospective association between organic food consumption and the risk of type 2 diabetes: findings from the NutriNet-Santé cohort study.
Kesse-Guyot, E, Rebouillat, P, Payrastre, L, Allès, B, Fezeu, LK, Druesne-Pecollo, N, Srour, B, Bao, W, Touvier, M, Galan, P, et al
The international journal of behavioral nutrition and physical activity. 2020;17(1):136
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The prevalence of type 2 diabetes (T2D) has significantly increased over recent decades, concomitantly to the obesity epidemic. Among the emergent risk factors, exposure to environmental contaminants including pesticides is of major concern. In fact, a recent European Food Safety Authority report indicated that 44% of conventional crop-based food contained at least one quantifiable pesticide residue, vs 6.5% in organic-labelled foods (OF). The aims of this study were (a) to investigate the prospective association between OF consumption and the risk of T2D, and (b) to estimate the mediation effect by the potential healthiness of a plant-based diet. This study is prospective cohort study based on the data from the web-based NutriNet-Santé study with an analysis sample of 33,256 participants. Results indicate an inverse association between organic plant-based food consumption and T2D risk especially in women. The association persisted after accounting for potential confounding effects of various factors, including lifestyles, dietary patterns and adiposity. Authors conclude that further studies are needed to replicate these findings for confirmation purposes and to elucidate underlying mechanisms.
Abstract
BACKGROUND Organic food (OF) consumption has substantially increased in high income countries, mostly driven by environmental concerns and health beliefs. Lower exposure to synthetic pesticides has been systematically documented among consumers of organic products compared to non-consumers. While experimental studies suggest that pesticides currently used in food production may be associated with type 2 diabetes (T2D), no well-conducted prospective studies have investigated the potential association between consumption of organic products and the risk of T2D, controlling for potential confounding factors. The objective of this prospective study was to estimate the association between OF consumption and the risk of T2D. METHODS A total of 33,256 participants (76% women, mean (SD) age: 53 years (14)) of the French NutriNet-Santé prospective cohort study who completed the organic food frequency questionnaire were included (2014-2019). The proportion of OF in the diet (as weight without drinking water) was computed. The associations between the proportion of OF in the diet (as 5% increment and as quintiles) and the risk of T2D were estimated using multivariable Hazard Ratio (HR) and 95% confidence interval (95% CI) derived from proportional hazards models adjusted for confounders (sociodemographic, anthropometric, lifestyle, medical and nutritional factors). RESULTS During follow-up (mean = 4.05 y, SD = 1.03 y, 134,990 person-years), 293 incident cases of T2D were identified. After adjustment for confounders including lifestyle (physical activity, smoking status, alcohol consumption) and nutritional quality of the diet assessed by the adherence to the French food-based dietary guidelines, OF consumption was associated with a lower risk of T2D. Participants with the highest quintile of OF consumption, compared with those with the lowest quintile, had 35% lower risk of T2D (95% CI = 0.43-0.97). Each increment of 5% in the proportion of OF in the diet was associated with 3% lower risk of T2D (HR 0.97, 95% CI = 0.95-0.99). CONCLUSIONS In this large prospective cohort study, OF consumption was inversely associated with the risk of T2D. Further experimental and prospective studies should be conducted to confirm these observations. CLINICAL TRIAL REGISTRY The study was registered at ClinicalTrials.gov ( NCT03335644 ).
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Ultraprocessed Food Consumption and Risk of Type 2 Diabetes Among Participants of the NutriNet-Santé Prospective Cohort.
Srour, B, Fezeu, LK, Kesse-Guyot, E, Allès, B, Debras, C, Druesne-Pecollo, N, Chazelas, E, Deschasaux, M, Hercberg, S, Galan, P, et al
JAMA internal medicine. 2020;(2):283-291
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IMPORTANCE Ultraprocessed foods (UPF) are widespread in Western diets. Their consumption has been associated in recent prospective studies with increased risks of all-cause mortality and chronic diseases such as cancer, cardiovascular diseases, hypertension, and dyslipidemia; however, data regarding diabetes are lacking. OBJECTIVE To assess the associations between consumption of UPF and risk of type 2 diabetes (T2D). DESIGN, SETTING, AND PARTICIPANTS In this population-based prospective cohort study, 104 707 participants aged 18 years or older from the French NutriNet-Santé cohort (2009-2019) were included. Dietary intake data were collected using repeated 24-hour dietary records (5.7 per participant on average), designed to register participants' usual consumption for more than 3500 different food items. These were categorized according to their degree of processing by the NOVA classification system. MAIN OUTCOMES AND MEASURES Associations between UPF consumption and risk of T2D were assessed using cause-specific multivariable Cox proportional hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors). RESULTS A total of 104 707 participants (21 800 [20.8%] men and 82 907 [79.2%] women) were included. Mean (SD) baseline age of participants was 42.7 (14.5) years. Absolute T2D rates in the lowest and highest UPF consumers were 113 and 166 per 100 000 person-years, respectively. Consumption of UPF was associated with a higher risk of T2D (multi-adjusted hazard ratio [HR] for an absolute increment of 10 in the percentage of UPF in the diet, 1.15; 95% CI, 1.06-1.25; median follow-up, 6.0 years; 582 252 person-years; 821 incident cases). These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet, for other metabolic comorbidities (HR, 1.13; 95% CI, 1.03-1.23), and for weight change (HR, 1.13; 95% CI, 1.01-1.27). The absolute amount of UPF consumption (grams per day) was consistently associated with T2D risk, even when adjusting for unprocessed or minimally processed food intake (HR for a 100 g/d increase, 1.05; 95% CI, 1.02-1.08). CONCLUSIONS AND RELEVANCE In this large observational prospective study, a higher proportion of UPF in the diet was associated with a higher risk of T2D. Even though these results need to be confirmed in other populations and settings, they provide evidence to support efforts by public health authorities to recommend limiting UPF consumption. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03335644.
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Association between sustainable dietary patterns and body weight, overweight, and obesity risk in the NutriNet-Santé prospective cohort.
Seconda, L, Egnell, M, Julia, C, Touvier, M, Hercberg, S, Pointereau, P, Lairon, D, Allès, B, Kesse-Guyot, E
The American journal of clinical nutrition. 2020;(1):138-149
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BACKGROUND Improving the sustainability of current food systems may prevent future public health, environmental, and social concerns. OBJECTIVE Our objective was to investigate the associations between sustainable dietary patterns, assessed using the Sustainable Diet Index (SDI), and the risk of obesity, overweight, and weight gain in French adults, with a prospective design. METHODS In 2014, the SDI was computed among 15,626 participants of the NutriNet-Santé study (of whom 76% were women) using data collected within the BioNutriNet project. The SDI ranges from 4 (lowest sustainability) to 20 points and includes 4 subindexes representing the 4 pillars of a sustainable diet. Longitudinal data of weight and height were collected yearly from 2014 to 2018. We used mixed models to estimate the associations between sex-specific quintiles (Qs) of the SDI and weight change and Cox proportional hazard models with different levels of adjustments to assess the association between sex-specific Qs of the SDI and risk of obesity and overweight (mean follow-up time: 2.8 y). RESULTS At baseline, a higher percentage of participants with overweight was observed in the first SDI Q, reflecting the lowest sustainable dietary patterns (Q1), than in Q5 (29.83% compared with 12.71%). Compared with Q5, a slight increase (at the population level) of almost 160 g/y was observed in Q1, whereas weight remained relatively stable among participants in other Qs. In total, 281 incident cases of obesity and 777 cases of overweight were identified during the follow-up. Participants in Q1 had a higher risk of obesity and overweight than participants in Q5 (HR comparing Q1 with Q5: 4.03; 95% CI: 2.42, 6.10; P-trend < 0.001; and HR comparing Q1 with Q5: 1.49; 95% CI: 1.13, 1.95; P-trend < 0.001, respectively). CONCLUSIONS The findings support a potential protective role for more sustainable diets to prevent the risk of weight gain, overweight, and obesity.This trial was registered at clinicaltrials.gov as NCT03335644.
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Ultra-processed food intake and risk of cardiovascular disease: prospective cohort study (NutriNet-Santé).
Srour, B, Fezeu, LK, Kesse-Guyot, E, Allès, B, Méjean, C, Andrianasolo, RM, Chazelas, E, Deschasaux, M, Hercberg, S, Galan, P, et al
BMJ (Clinical research ed.). 2019;:l1451
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OBJECTIVE To assess the prospective associations between consumption of ultra-processed foods and risk of cardiovascular diseases. DESIGN Population based cohort study. SETTING NutriNet-Santé cohort, France 2009-18. PARTICIPANTS 105 159 participants aged at least 18 years. Dietary intakes were collected using repeated 24 hour dietary records (5.7 for each participant on average), designed to register participants' usual consumption of 3300 food items. These foods were categorised using the NOVA classification according to degree of processing. MAIN OUTCOME MEASURES Associations between intake of ultra-processed food and overall risk of cardiovascular, coronary heart, and cerebrovascular diseases assessed by multivariable Cox proportional hazard models adjusted for known risk factors. RESULTS During a median follow-up of 5.2 years, intake of ultra-processed food was associated with a higher risk of overall cardiovascular disease (1409 cases; hazard ratio for an absolute increment of 10 in the percentage of ultra-processed foods in the diet 1.12 (95% confidence interval 1.05 to 1.20); P<0.001, 518 208 person years, incidence rates in high consumers of ultra-processed foods (fourth quarter) 277 per 100 000 person years, and in low consumers (first quarter) 242 per 100 000 person years), coronary heart disease risk (665 cases; hazard ratio 1.13 (1.02 to 1.24); P=0.02, 520 319 person years, incidence rates 124 and 109 per 100 000 person years, in the high and low consumers, respectively), and cerebrovascular disease risk (829 cases; hazard ratio 1.11 (1.01 to 1.21); P=0.02, 520 023 person years, incidence rates 163 and 144 per 100 000 person years, in high and low consumers, respectively). These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet (saturated fatty acids, sodium and sugar intakes, dietary fibre, or a healthy dietary pattern derived by principal component analysis) and after a large range of sensitivity analyses. CONCLUSIONS In this large observational prospective study, higher consumption of ultra-processed foods was associated with higher risks of cardiovascular, coronary heart, and cerebrovascular diseases. These results need to be confirmed in other populations and settings, and causality remains to be established. Various factors in processing, such as nutritional composition of the final product, additives, contact materials, and neoformed contaminants might play a role in these associations, and further studies are needed to understand better the relative contributions. Meanwhile, public health authorities in several countries have recently started to promote unprocessed or minimally processed foods and to recommend limiting the consumption of ultra-processed foods. STUDY REGISTRATION ClinicalTrials.gov NCT03335644.