Food additive emulsifiers and the risk of type 2 diabetes: analysis of data from the NutriNet-Santé prospective cohort study.

BACKGROUND: Experimental studies have suggested potential detrimental effects of emulsifiers on gut microbiota, inflammation, and metabolic perturbations. We aimed to investigate the associations between exposures to food additive emulsifiers and the risk of type 2 diabetes in a large prospective cohort of French adults. METHODS: We analysed data from 104 139 adults enrolled in the French NutriNet-Santé prospective cohort study from May 1, 2009, to April 26, 2023; 82 456 (79·2%) were female and the mean age was 42·7 years (SD 14·5). Dietary intakes were assessed with three 24 h dietary records collected over three non-consecutive days, every 6 months. Exposure to additive emulsifiers was evaluated through multiple food composition databases and ad-hoc laboratory assays. Associations between cumulative time-dependent exposures to food additive emulsifiers and the risk of type 2 diabetes were characterised with multivariable proportional hazards Cox models adjusted for known risk factors. The NutriNet-Santé study is registered at ClinicalTrials.gov (NCT03335644). FINDINGS: Of 104 139 participants, 1056 were diagnosed with type 2 diabetes during follow-up (mean follow-up duration 6·8 years [SD 3·7]). Intakes of the following emulsifiers were associated with an increased risk of type 2 diabetes: total carrageenans (hazard ratio [HR] 1·03 [95% CI 1·01-1·05] per increment of 100 mg per day, p<0·0001), carrageenans gum (E407; HR 1·03 [1·01-1·05] per increment of 100 mg per day, p<0·0001), tripotassium phosphate (E340; HR 1·15 [1·02-1·31] per increment of 500 mg per day, p=0·023), acetyl tartaric acid esters of monoglycerides and diglycerides of fatty acids (E472e; HR 1·04 [1·00-1·08] per increment of 100 mg per day, p=0·042), sodium citrate (E331; HR 1·04 [1·01-1·07] per increment of 500 mg per day, p=0·0080), guar gum (E412; HR 1·11 [1·06-1·17] per increment of 500 mg per day, p<0·0001), gum arabic (E414; HR 1·03 [1·01-1·05] per increment of 1000 mg per day, p=0·013), and xanthan gum (E415, HR 1·08 [1·02-1·14] per increment of 500 mg per day, p=0·013). INTERPRETATION: We found direct associations between the risk of type 2 diabetes and exposures to various food additive emulsifiers widely used in industrial foods, in a large prospective cohort of French adults. Further research is needed to prompt re-evaluation of regulations governing the use of additive emulsifiers in the food industry for better consumer protection. FUNDING: European Research Council, French National Cancer Institute, French Ministry of Health, IdEx Université de Paris, and Bettencourt-Schueller Foundation.

Food additive emulsifiers and risk of cardiovascular disease in the NutriNet-Santé cohort: prospective cohort study.

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. TRIAL REGISTRATION: ClinicalTrials.gov NCT03335644.

Relationship between Sucrose Taste Detection Thresholds and Preferences in Children, Adolescents, and Adults.

To address gaps in knowledge, our objectives were to (1) to determine whether there are age-related changes in sweet taste detection thresholds, as has been observed for sweet taste preferences, and (2) determine whether detection thresholds and taste preferences were significantly related to each other from childhood to adulthood. We combined data from studies that used the same validated psychophysical techniques to measure sucrose taste detection threshold and the most preferred sucrose concentration in children (n = 108), adolescents (n = 172), and adults (n = 205). There were significant effects of age group on both sucrose detection thresholds (p < 0.001) and most preferred sucrose concentration (p < 0.001). While children had higher sucrose detection thresholds than adolescents, who in turn tended to have higher detection thresholds than adults, both children and adolescent most preferred sucrose concentrations were higher than that of adults (all p < 0.05). Among each age group, and when combined, the lowest sucrose concentration detected was not significantly correlated with the most preferred sucrose concentration (all p > 0.18). These data provide further evidence that age-related changes in sucrose taste preferences that occur during adolescence cannot be explained by changes in taste sensitivity and that these two dimensions of sweet taste undergo distinct developmental trajectories from childhood to adulthood.

Effects of Sucralose Ingestion versus Sucralose Taste on Metabolic Responses to an Oral Glucose Tolerance Test in Participants with Normal Weight and Obesity: A Randomized Crossover Trial.

Here, we tested the hypothesis that sucralose differentially affects metabolic responses to labeled oral glucose tolerance tests (OGTTs) in participants with normal weight and obesity. Participants (10 with normal weight and 11 with obesity) without diabetes underwent three dual-tracer OGTTs preceded, in a randomized order, by consuming sucralose or water, or by tasting and expectorating sucralose (e.g., sham-fed; sweetness control). Indices of ß-cell function and insulin sensitivity (SI) were estimated using oral minimal models of glucose, insulin, and C-peptide kinetics. Compared with water, sucralose ingested (but not sham-fed) resulted in a 30 ± 10% increased glucose area under the curve in both weight groups. In contrast, the insulin response to sucralose ingestion differed depending on the presence of obesity: decreased within 20-40 min of the OGTT in normal-weight participants but increased within 90-120 min in participants with obesity. Sham-fed sucralose similarly decreased insulin concentrations within 60 min of the OGTT in both weight groups. Sucralose ingested (but not sham-fed) increased SI in normal-weight participants by 52 ± 20% but did not affect SI in participants with obesity. Sucralose did not affect glucose rates of appearance or ß-cell function in either weight group. Our data underscore a physiological role for taste perception in postprandial glucose responses, suggesting sweeteners should be consumed in moderation.

Differences between Measured Total Nitrogen Losses in Spent Peritoneal Dialysate Effluent and Estimated Nitrogen Losses.

OBJECTIVE: Patients treated by peritoneal dialysis (PD) are at increased risk of muscle wasting, and clinical guidelines recommend assessing dietary intake, by calculating protein equivalent of nitrogen appearance (PNA) to assure protein sufficiency. The PNA equations were developed many years ago, and we wished to re-evaluate them by comparing estimated and measured peritoneal nitrogen losses. DESIGN AND METHODS: This is a cross-sectional observational cohort study. The study setting was an outpatient PD center of a university hospital and the study subjects included 67 patients undergoing PD, in which 61.2% were males, and the median age was 67.3 (53.2-79.4) years. The nitrogen content of 24-hour spent peritoneal dialysate by automated chemiluminescence analyzer was measured and compared with estimates of nitrogen losses based on dialysate urea loss using the Bergstrom, Randerson, and Blumenkrantz equations. RESULTS: Measured total dialysate nitrogen was more than urea nitrogen equivalent, 5.79 ± 4.07 versus 2.66 ± 1.67 g/day (P < .001). Each equation has an inflation factor to compensate for nonurea protein losses; however, measured nitrogen loss was 27.7 (15.5-59.6) g/day versus Bergstrom, 16.5 (9.8-27.1); Randerson, 16.4 (9.8-27.3); and Blumenkrantz, 12.9 (7.9-25.4) g/day, P < .001. The BlandAltman analysis demonstrated systematic bias with increasing underestimation by these equations with increasing measured nitrogen losses (r = 0.74, P < .001). CONCLUSION: Our findings demonstrate that at higher protein losses, the currently used predictive equations underestimate the amount lost. It is important to attempt to compensate the iatrogenic protein loss by recommending the appropriate intake of dietary protein to patients, in an attempt to minimize muscle wasting. This discrepancy may have arisen because of the characteristics of newer PD prescriptions and change in patient demographics. We propose a new equation PNA g/day = 0.31 × (urea loss mmol) + 7.17, which will require prospective validation in additional studies.

Protein Losses and Urea Nitrogen Underestimate Total Nitrogen Losses in Peritoneal Dialysis and Hemodialysis Patients.

OBJECTIVE: Muscle wasting is associated with increased mortality and is commonly reported in dialysis patients. Hemodialysis (HD) and peritoneal dialysis (PD) treatments lead to protein losses in effluent dialysate. We wished to determine whether changes in current dialysis practice had increased therapy-associated nitrogen losses. DESIGN: Cross-sectional cohort study. METHODS: Measurement of total protein, urea and total nitrogen in effluent dialysate from 24-hour collections from PD patients, and during haemodiafiltration (HDF) and haemodialysis (HD) sessions. SUBJECTS: One hundred eight adult dialysis patients. INTERVENTION: Peritoneal dialysis, high-flux haemodialysis and haemodiafiltration. MAIN OUTCOME MEASURE: Total nitrogen and protein losses. RESULTS: Dialysate protein losses were measured in 68 PD and 40 HD patients. Sessional losses of urea (13.9 [9.2-21.1] vs. 4.8 [2.8-7.8] g); protein (8.6 [7.2-11.1] vs. 6.7 [3.9-11.1] g); and nitrogen (11.5 [8.7-17.7] vs. 4.9 [2.6-9.5] g) were all greater for HD than PD, P < .001. Protein-derived nitrogen was 71.9 (54.4-110.4) g for HD and 30.8 (16.1-59.6) g for PD. Weekly protein losses were lower with HD 25.9 (21.5-33.4) versus 46.6 (27-77.6) g/week, but nitrogen losses were similar. We found no difference between high-flux HD and HDF: urea (13.5 [8.8-20.6] vs. 15.3 [10.5-25.5] g); protein (8.8 [7.3-12.2] vs. 7.6 [5.8-9.0] g); and total nitrogen (11.6 [8.3-17.3] vs. 10.8 [8.9-22.5] g). Urea nitrogen (UN) only accounted for 45.1 (38.3-51.0)% PD and 63.0 (55.3-62.4)% HD of total nitrogen losses. CONCLUSION: Although sessional losses of protein and UN were greater with HD, weekly losses were similar between modalities. We found no differences between HD and HDF. However, total nitrogen losses were much greater than the combination of protein and UN, suggesting greater nutritional losses with dialysis than previously reported.