Food additive mixtures and risk of cardiovascular and hypertension in the NutriNet-Santé cohort

Abstract Background Modern diets expose individuals to mixtures of food additives. Emerging experimental and epidemiological data suggest that certain additive combinations may produce synergistic harmful effects. This study investigated associations between food additive mixtures in the NutriNet-Santé cohort and the incidence of hypertension and cardiovascular disease (CVD), including cerebrovascular (CVA) and coronary heart disease (CHD). Methods Among 110,021 French adults (mean age 43.7 ± 14.3 years; 79.2 % women) without CVD or hypertension at baseline, each completed at least two 24-hour dietary recalls capturing commercial brands of industrial foods. Additive intakes were quantified via food composition databases and laboratory analyses in food matrixes. Non-Negative Matrix Factorization identified food additive mixtures. Associations between cumulative, time-varying categorical exposures and incident CVD and hypertension were estimated with multivariable Cox models adjusted for confounders. Results Over a median follow-up of 7.91 years, 5,544, 2,450, 1,142 and 1,308 participants developed hypertension, CVD, CVA and CHD, respectively. Mixture 1 (sodium carbonates, diphosphates, glycerol, ammonium carbonates) was associated with hypertension (HR = 1.15 [1.07-1.23]), CVA (1.06 [1.01-1.12]) and CHD (1.05 [0.98-1.13]); Mixture 2 (modified starches, pectin, guar gum, carrageenan) with hypertension (1.13 [1.05-1.21]), CVD (1.10 [1.04-1.15]) and CHD (1.14 [1.07-1.22]); Mixture 3 (magnesium carbonates, riboflavin, α-tocopherol, ammonium carbonates) with CVA (1.06 [1.01-1.11]); and Mixtures 4 (ammonium & sodium carbonates, diphosphates, α-tocopherol) and 5 (citric acid, sodium citrates, phosphoric acid, acesulfame-K) each with hypertension (1.17 [1.10-1.26] and 1.18 [1.10-1.26]). Conclusions New epidemiological data show that mixtures of food additives may harm cardiometabolic health, implying regulations should assess combined exposures instead of single additives. Key messages • Food additive mixtures may adversely impact cardiometabolic health, suggesting a need to reconsider regulatory practices focused on individual additives. • Further research is essential to understand the mechanisms linking additive mixtures to health outcomes.