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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 .

AbstractObjectiveTo investigate the association between intake of food additive preservatives and cancer incidence in a large prospective cohort.DesignProspective cohort.SettingFrench NutriNet-Santé cohort, 2009-23.Participants105 260 participants (≥15 years) without prevalent cancer who completed at least two 24 hour dietary records at baseline.Main outcome measuresCumulative time dependent intake of preservatives, including those in industrial food brands, assessed using repeated 24 hour dietary records and evaluated through multiple composition databases and ad hoc laboratory assays in food products for the most frequently consumed additive-food pairs. Associations between intake of three categories of preservatives (defined as sex specific thirds if preservative was consumed by at least a third of participants, otherwise defined as non-consumers and lower or higher consumers separated by the sex specific median) and cancer incidence were characterised using multivariable proportional hazards Cox models adjusted for potential confounders.ResultsMean age of participants was 42.0 years (standard deviation (SD 14.5) years), and 78.7% were women. 4226 participants received a diagnosis of incident cancer (mean follow-up 7.57 (SD 4.56) years), comprising 1208 breast, 508 prostate, 352 colorectal, and 2158 other cancers). Higher intakes of several preservatives were associated with higher cancer incidence: total non-antioxidants with overall cancer (hazard ratio for higher v non-consumers or lower consumers 1.16 (95% confidence interval (CI) 1.07 to 1.26); absolute risk of cancer at age 60 years, respectively, 13.3%, 12.1%) and breast cancer (1.22 (1.05 to 1.41); 5.7%, 4.8%); total sorbates, specifically potassium sorbate, with overall cancer (1.14 (1.04 to 1.24); 13.4%, 11.8%) and breast cancer (1.26 (1.07 to 1.49); 5.7%, 4.6%); total sulfites with overall cancer (1.12 (1.02 to 1.24); 13.4%, 11.9%); potassium metabisulfite with overall cancer (1.11 (1.03 to 1.20); 13.5%, 12.0%) and breast cancer (1.20 (1.04 to 1.38); 5.7%, 4.9%); sodium nitrite with prostate cancer (1.32 (1.02 to 1.70); 4.2%, 3.4%); potassium nitrate with overall cancer (1.13 (1.05 to 1.23); 14.0%, 12.0%) and breast cancer (1.22 (1.05 to 1.41); 5.9%, 4.8%); total acetates with overall cancer (1.15 (1.06 to 1.25); 14.3%, 12.2%) and breast cancer (1.25 (1.07 to 1.45); 6.1%, 4.9%); acetic acid with overall cancer (1.12 (1.01 to 1.25); 14.4%, 12.4%); and sodium erythorbate with overall cancer (1.12 (1.04 to 1.22); 13.5%, 11.9%) and breast cancer (1.21 (1.04 to 1.41); 5.7%, 4.8%). 11 of the 17 individually studied preservatives were not associated with cancer incidence.ConclusionMultiple positive associations between intake of preservatives widely used in industrial foods and higher cancer incidence (overall, breast, and prostate) were observed in this large prospective cohort. Epidemiology based on health effect biomarkers and experimental research are needed to gain insight into outcome pathways. If confirmed, these new data call for the re-evaluation of regulations governing the food industry’s use of these additives, to improve consumer protection. In the meantime, the findings support recommendations for consumers to favour freshly made, minimally processed foods.Trial registrationClinicalTrials.gov NCT03335644.

Mixtures of food additives are daily consumed worldwide by billions of people. So far, safety assessments have been performed substance by substance due to lack of data on the effect of multiexposure to combinations of additives. Our objective was to identify most common food additive mixtures, and investigate their associations with type 2 diabetes incidence in a large prospective cohort. Participants (n = 108,643, mean follow-up =  7.7 years (standard deviation (SD) =  4.6), age =  42.5 years (SD =  14.6), 79.2% women) were adults from the French NutriNet-Santé cohort (2009-2023). Dietary intakes were assessed using repeated 24h-dietary records, including industrial food brands. Exposure to food additives was evaluated through multiple food composition databases and laboratory assays. Mixtures were identified through nonnegative matrix factorization (NMF), and associations with type 2 diabetes incidence were assessed using Cox models adjusted for potential socio-demographic, anthropometric, lifestyle and dietary confounders. A total of 1,131 participants were diagnosed with type 2 diabetes. Two out of the five identified food additive mixtures were associated with higher type 2 diabetes incidence: the first mixture included modified starches, pectin, guar gum, carrageenan, polyphosphates, potassium sorbates, curcumin, and xanthan gum (hazard ratio (HR)per an increment of 1SD of the NMF mixture score = 1.08 [1.02, 1.15], p = 0.006), and the other mixture included citric acid, sodium citrates, phosphoric acid, sulphite ammonia caramel, acesulfame-K, aspartame, sucralose, arabic gum, malic acid, carnauba wax, paprika extract, anthocyanins, guar gum, and pectin (HR = 1.13 [1.08,1.18], p < 0.001). No association was detected for the three remaining mixtures: HR =  0.98 [0.91, 1.06], p = 0.67; HR =  1.02 [0.94, 1.10], p = 0.68; and HR =  0.99 [0.92, 1.07], p = 0.78. Several synergistic and antagonist interactions between food additives were detected in exploratory analyses. Residual confounding as well as exposure or outcome misclassifications cannot be entirely ruled out and causality cannot be established based on this single observational study. This study revealed positive associations between exposure to two widely consumed food additive mixtures and higher type 2 diabetes incidence. Further experimental research is needed to depict underlying mechanisms, including potential synergistic/antagonist effects. These findings suggest that a combination of food additives may be of interest to consider in safety assessments, and they support public health recommendations to limit nonessential additives. The NutriNet-Santé cohort is registered at clinicaltrials.gov (NCT03335644). https://clinicaltrials.gov/study/NCT03335644.

Experimental studies suggested potential adverse effects of preservative food additives, but epidemiological data are lacking. We aim to investigate associations between exposure to these compounds and type 2 diabetes incidence in the NutriNet-Santé prospective cohort (n = 108,723; 79.2%women; mean age=42.5 (SD = 14.6); France, 2009-2023). Dietary intakes are assessed using repeated 24h-dietary records. Exposure is evaluated through multiple composition databases and ad-hoc laboratory assays in food matrices. Associations between cumulative exposures to preservatives and diabetes incidence are characterised using multi-adjusted Cox models. The sum of total preservatives encompasses 58 substances. Among those, 17 are consumed by at least 10% of the study population and thus individually investigated. Thirteen (12 after multiple test correction) widely used individual preservatives are associated with higher diabetes incidence (n=1131cases): potassium sorbate, potassium metabisulfite, sodium nitrite, acetic, citric and phosphoric acids, sodium acetates, calcium propionate, sodium ascorbate, alpha-tocopherol, sodium erythorbate, and rosemary extracts. These findings call for their safety re-evaluation and support recommendations to favour fresh and minimally processed foods without superfluous additives. Trial registration: The NutriNet-Santé cohort is registered at clinicaltrials.gov (NCT03335644). Exposure to twelve widely used preservative food additives are associated with a higher incidence of type 2 diabetes in the French NutriNet-Santé cohort of 108,723 adults, supporting recommendations to favour fresh and minimally processed foods

BackgroundEmulsifiers 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 findingsThis 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.ConclusionsIn 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 registrationClinicalTrials.gov NCT03335644.

Objective: To assess the associations between exposure to food additive emulsifiers and risk of cardiovascular disease (CVD).Design: Prospective cohort study.Setting: French NutriNet-Santé study, 2009-21.Participants: 95 442 adults (>18 years) without prevalent CVD who completed at least three 24 hour dietary records during the first two years of follow-up.Main outcome measures: Associations between intake of food additive emulsifiers (continuous (mg/day)) and risk of CVD, coronary heart disease, and cerebrovascular disease characterised using multivariable proportional hazard Cox models to compute hazard ratios for each additional standard deviation (SD) of emulsifier intake, along with 95% confidence intervals.Results: Mean age was 43.1 (SD 14.5) years, and 79.0% (n=75 390) of participants were women. During follow-up (median 7.4 years), 1995 incident CVD, 1044 coronary heart disease, and 974 cerebrovascular disease events were diagnosed. Higher intake of celluloses (E460-E468) was found to be positively associated with higher risks of CVD (hazard ratio for an increase of 1 standard deviation 1.05, 95% confidence interval 1.02 to 1.09, P=0.003) and coronary heart disease (1.07, 1.02 to 1.12, P=0.004). Specifically, higher cellulose E460 intake was linked to higher risks of CVD (1.05, 1.01 to 1.09, P=0.007) and coronary heart disease (1.07, 1.02 to 1.12, P=0.005), and higher intake of carboxymethylcellulose (E466) was associated with higher risks of CVD (1.03, 1.01 to 1.05, P=0.004) and coronary heart disease (1.04, 1.02 to 1.06, P=0.001). Additionally, higher intakes of monoglycerides and diglycerides of fatty acids (E471 and E472) were associated with higher risks of all outcomes. Among these emulsifiers, lactic ester of monoglycerides and diglycerides of fatty acids (E472b) was associated with higher risks of CVD (1.06, 1.02 to 1.10, P=0.002) and cerebrovascular disease (1.11, 1.06 to 1.16, P<0.001), and citric acid ester of monoglycerides and diglycerides of fatty acids (E472c) was associated with higher risks of CVD (1.04, 1.02 to 1.07, P=0.004) and coronary heart disease (1.06, 1.03 to 1.09, P<0.001). High intake of trisodium phosphate (E339) was associated with an increased risk of coronary heart disease (1.06, 1.00 to 1.12, P=0.03). Sensitivity analyses showed consistent associations.Conclusion: This study found positive associations between risk of CVD and intake of five individual and two groups of food additive emulsifiers widely used in industrial foods.

Due in part to recent progress in root genetics and genomics, increasing attention is being devoted to root system architecture (RSA) for the improvement of drought tolerance. The focus is generally set on deep roots, expected to improve access to soil water resources during water deficit episodes. Surprisingly, our quantitative understanding of the role of RSA in the uptake of soil water remains extremely limited, which is mainly due to the inherent complexity of the soil–plant continuum. Evidently, there is a need for plant biologists and hydrologists to develop together their understanding of water movement in the soil–plant system. Using recent quantitative models coupling the hydraulic behaviour of soil and roots in an explicit 3D framework, this paper illustrates that the contribution of RSA to root water uptake is hardly separable from the hydraulic properties of the roots and of the soil. It is also argued that the traditional view that either the plant or the soil should be dominating the patterns of water extraction is not generally appropriate for crops growing with a sub-optimal water supply. Hopefully, in silico experiments using this type of model will help explore how water fluxes driven by soil and plant processes affect soil water availability and uptake throughout a growth cycle and will embed the study of RSA within the domains of root hydraulic architecture and sub-surface hydrology.

As water often limits crop production, a more complete understanding of plant water capture and transport is necessary. Here, we developed MECHA, a mathematical model that computes the flow of water across the root at the scale of walls, membranes, and plasmodesmata of individual cells, and used it to test hypotheses related to root water transport in maize (Zea mays). The model uses detailed root anatomical descriptions and a minimal set of experimental cell properties, including the conductivity of plasma membranes, cell walls, and plasmodesmata, which yield quantitative and scale-consistent estimations of water pathways and root radial hydraulic conductivity (k r). MECHA revealed that the mainstream hydraulic theories derived independently at the cell and root segment scales are compatible only if osmotic potentials within the apoplastic domains are uniform. The results suggested that the convection-diffusion of apoplastic solutes explained most of the offset between estimated k r in pressure clamp and osmotic experiments, while the contribution of water-filled intercellular spaces was limited. Furthermore, sensitivity analyses quantified the relative impact of cortex and endodermis cell conductivity of plasma membranes on root k r and suggested that only the latter contributed substantially to k r due to the composite nature of water flow across roots. The explicit root hydraulic anatomy framework brings insights into contradictory interpretations of experiments from the literature and suggests experiments to efficiently address questions pertaining to root water relations. Its scale consistency opens avenues for cross-scale communication in the world of root hydraulics.

Over the last decade, investigations on root water uptake have evolved toward a deeper integration of the soil and roots compartment properties, with the goal of improving our understanding of water acquisition from drying soils. This evolution parallels the increasing attention of agronomists to suboptimal crop production environments. Recent results have led to the description of root system architectures that might contribute to deep-water extraction or to water-saving strategies. In addition, the manipulation of root hydraulic properties would provide further opportunities to improve water uptake. However, modeling studies highlight the role of soil hydraulics in the control of water uptake in drying soil and call for integrative soil-plant system approaches.