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).
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.
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.
ClinicalTrials.gov NCT03335644.
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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
Prevention of chronic diseases has therefore been considered a public health challenge in the past decades 2. Besides physical activity, the nutritional quality of the diet is a major modifiable risk ...factor for weight management, with strong levels of evidence for protective factors (i.e., dietary fibre, Mediterranean diets) and risk factors (i.e., high energy density, free sugars, sugar sweetened drinks, and Western-type diets) 5,7. Another characteristic of UPFs is that they are obtained after sequences of several processes, such as high-temperature extrusion, moulding, and pre-frying, and include several food additives and industrial ingredients used to imitate or enhance sensory qualities of foods or to disguise unpalatable aspects of the final product; they are also often in contact with synthetic packaging materials for long periods 25. Consistently, several cross-sectional and ecological studies have substantiated a positive association between UPF consumption and obesity 23,35–39, but prospective studies are lacking, as only 2 of them—one in Spain 40 and one in Brazil 41—were conducted; both relied on dietary data from food frequency questionnaires (FFQs) and studied the contribution of UPF to energy intake and therefore did not account for low-calorie and artificially sweetened products. Several indicators of the nutritional quality of the diet were also computed based on average dietary intakes from baseline 24-hour dietary records and were used as covariates: daily nutrient intake (sugar, fibre, sodium, and saturated fatty acid SFA) calculated using the food composition database; consumptions of several food groups (fruit, vegetables, and sugary drinks); and healthy and Western dietary patterns, derived from Principal Component Analysis (see Method D in S1 Appendix).
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Food additives (e.g. artificial sweeteners, emulsifiers, dyes, etc.) are ingested by billions of individuals daily. Some concerning results, mainly derived from animal and/or cell-based experimental ...studies, have recently emerged suggesting potential detrimental effects of several widely consumed additives. Profiles of additive exposure as well as the potential long-term impact of multiple exposure on human health are poorly documented. This work aimed to estimate the usual intake of food additives among participants of the French NutriNet-Santé cohort and to identify and describe profiles of exposure (single substances and mixtures). Overall, 106,489 adults from the French NutriNet-Santé cohort study (2009-ongoing) were included. Consumption of 90 main food additives was evaluated using repeated 24 h dietary records including information on brands of commercial products. Qualitative information (as presence/absence) of each additive in food products was determined using 3 large-scale composition databases (OQALI, Open Food Facts, GNPD), accounting for the date of consumption of the product. Quantitative ingested doses were estimated using a combination of laboratory assays on food matrixes (n = 2677) and data from EFSA and JECFA. Exposure was estimated in mg per kg of body weight per day. Profiles of exposure to food additive mixtures were extracted using Non-negative Matrix Factorization (NMF) followed by k-means clustering as well as Graphical Lasso. Sociodemographic and dietary comparison of clusters of participants was performed by Chi-square tests or linear regressions. Data were weighted according to the national census. Forty-eight additives were consumed by more than 10% of the participants, with modified starches and citric acid consumed by more than 90%. The top 50 also included several food additives for which potential adverse health effects have been suggested by recent experimental studies: lecithins (86.6% consumers), mono- and diglycerides of fatty acids (78.1%), carrageenan (77.5%), sodium nitrite (73.9%), di-, tri- and polyphosphates (70.1%), potassium sorbate (65.8%), potassium metabisulphite (44.8%), acesulfame K (34.0%), cochineal (33.9%), potassium nitrate (31.6%), sulfite ammonia caramel (28.8%), bixin (19.5%), monosodium glutamate (15.1%) and sucralose (13.5%). We identified and described five clusters of participants more specifically exposed to five distinct additive mixtures and one additional cluster gathering participants with overall low additive exposure. Food additives, including several for which health concerns are currently debated, were widely consumed in this population-based study. Furthermore, main mixtures of additives were identified. Their health impact and potential cocktail effects should be explored in future epidemiological and experimental studies.
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More than 330 food additives (e.g. artificial sweeteners, emulsifiers, dyes) are authorized in Europe, with a great variability of use across food products.
The objective of this study was to ...investigate the distribution and co-occurrence of food additives in a large-scale database of foods and beverages available on the French market.
The open access crowdsourced Open Food Facts database (https://world.openfoodfacts.org/) was used to retrieve the composition of food and beverage products commonly marketed on the French market (n = 126,556), based on the ingredients list. Clustering of food additive variables was used in order to determine groups of additives frequently co-occurring in food products. The clusters were confirmed by network analysis, using the eLasso method.
Fifty-three-point eight percent of food products contained at least 1 food additive and 11.3% at least 5. Food categories most likely to contain food additives (in more than 85% of food items) were artificially sweetened beverages, ice creams, industrial sandwiches, biscuits and cakes. The most frequently used food additives were citric acid, lecithins and modified starches (>10,000 products each). Some food additives with suspected health effects also pertained to the top 50: sodium nitrite, potassium nitrate, carrageenan, monosodium glutamate, sulfite ammonia caramel, acesulfame K, sucralose, (di/tri/poly) phosphates, mono- and diglycerides of fatty acids, potassium sorbate, cochineal, potassium metabisulphite, sodium alginate, and bixin (>800 food products each). We identified 6 clusters of food additives frequently co-occurring in food products.
Food additives are widespread in industrial French products and some clusters of additives frequently co-occurring in food products were identified. These results pave the way to future etiological studies merging composition data to food consumption data to investigate their association with chronic disease risk, in particular potential 'cocktail effects'.
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AbstractObjectivesTo study the associations between artificial sweeteners from all dietary sources (beverages, but also table top sweeteners, dairy products, etc), overall and by molecule (aspartame, ...acesulfame potassium, and sucralose), and risk of cardiovascular diseases (overall, coronary heart disease, and cerebrovascular disease).DesignPopulation based prospective cohort study (2009-21).SettingFrance, primary prevention research.Participants103 388 participants of the web based NutriNet-Santé cohort (mean age 42.2±14.4, 79.8% female, 904 206 person years). Dietary intakes and consumption of artificial sweeteners were assessed by repeated 24 h dietary records, including brand names of industrial products.Main outcomes measuresAssociations between sweeteners (coded as a continuous variable, log10 transformed) and cardiovascular disease risk, assessed by multivariable adjusted Cox hazard models.ResultsTotal artificial sweetener intake was associated with increased risk of cardiovascular diseases (1502 events, hazard ratio 1.09, 95% confidence interval 1.01 to 1.18, P=0.03); absolute incidence rate in higher consumers (above the sex specific median) and non-consumers was 346 and 314 per 100 000 person years, respectively. Artificial sweeteners were more particularly associated with cerebrovascular disease risk (777 events, 1.18, 1.06 to 1.31, P=0.002; incidence rates 195 and 150 per 100 000 person years in higher and non-consumers, respectively). Aspartame intake was associated with increased risk of cerebrovascular events (1.17, 1.03 to 1.33, P=0.02; incidence rates 186 and 151 per 100 000 person years in higher and non-consumers, respectively), and acesulfame potassium and sucralose were associated with increased coronary heart disease risk (730 events; acesulfame potassium: 1.40, 1.06 to 1.84, P=0.02; incidence rates 167 and 164; sucralose: 1.31, 1.00 to 1.71, P=0.05; incidence rates 271 and 161).ConclusionsThe findings from this large scale prospective cohort study suggest a potential direct association between higher artificial sweetener consumption (especially aspartame, acesulfame potassium, and sucralose) and increased cardiovascular disease risk. Artificial sweeteners are present in thousands of food and beverage brands worldwide, however they remain a controversial topic and are currently being re-evaluated by the European Food Safety Authority, the World Health Organization, and other health agencies.Trial registrationClinicalTrials.gov NCT03335644
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.
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.
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.
ClinicalTrials.gov NCT03335644 (https://clinicaltrials.gov/ct2/show/NCT03335644).
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The present study aims to describe ultra-processed food (UPF) consumption in a representative sample of French adults and to evaluate the association between UPF consumption and socioeconomic ...characteristics and nutritional profile of the diet. This is a cross-sectional study using food consumption data from the Étude Nationale Nutrition Santé (ENNS), conducted with 2642 participants (18-74 years old), between February 2006 and March 2007 in France. Dietary data were collected through three 24-h dietary recalls. All food and beverages were classified according to the NOVA classification. The energy contribution of NOVA food groups to total energy intake was presented by categories of sociodemographic characteristics. Linear and logistic regression models were used to estimate the association between the percentage of UPF in the diet with nutritional indicators. The mean daily energy consumption of the adult French population was 2111 kcal, of which 31.1% came from UPF. This percentage was higher among younger individuals, and in the urban area, and lower among individuals with incomplete high school and individuals who were retired. The consumption of UPF was positively associated with the dietary energy density and the dietary contents of total carbohydrates, free sugar, and total and saturated fat, as well as with inadequate dietary energy density, saturated fat, free sugar, and fiber intakes.
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.
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.
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.
ClinicalTrials.gov NCT03335644.
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Background Nitrates and nitrites are used as food additives in processed meats. They are also commonly ingested from water and several foods. Several short-term clinical studies suggested beneficial ...effects of dietary nitrates on blood pressure, while deleterious effects on oxidative damage have been suggested in some experimental studies. However, there is a lack of evidence from longitudinal epidemiological studies linking foods and water-originated and additives-originated nitrites and nitrates, separately, to hypertension and cardiovascular diseases risk. We aimed to study these associations in a large population-based cohort. Methods and Results Overall, 106 288 adults from the French NutriNet-Santé cohort (2009-2022) were included. Associations between nitrites and nitrates intakes and hypertension and cardiovascular disease risks were assessed using multi-adjusted Cox proportional hazard models. During follow-up, 3810 incident cases of hypertension and 2075 cases of cardiovascular diseases were ascertained. Participants with higher intakes of additives-originated nitrites (sodium nitrite in particular European code e250) had a higher hypertension risk compared with nonconsumers (hazard ratio, 1.19 95% CI, 1.08-1.32,
=0.001, and 1.19 95% CI, 1.08-1.32,
=0.002), respectively. No association was detected between foods and water-originated nitrites, or nitrates with hypertension risk (all
values >0.3). We found no association between nitrites or nitrates and risks of cardiovascular diseases (all
values >0.2). Conclusions These results do not support a protective role of nitrites or nitrates in cardiovascular health. Instead, they suggest a positive association between nitrites from food additives and hypertension risk, which needs confirmation in other large-scale studies. These findings provide new evidence in the context of current discussions about updating regulations on the use of nitrites as food additives.
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