Food additive mixtures and hypertension and cardiovascular diseases incidence in the NutriNet-Santé prospective cohort

Abstract

Abstract Background Emerging experimental and epidemiological studies suggest that certain combinations of food additives may exert harmful effects that go beyond those observed for individual substances. This study aimed to investigate the associations between chronic exposure to food additive mixtures and the incidence of hypertension and cardiovascular disease (CVD), including cerebrovascular accident (CVA) and coronary heart disease (CHD), in the NutriNet-Santé cohort (2009–2024). Methods A total of 112,050 French adults (mean age: 42.8 years, SD: 14.6; 79.0% women) were included. Participants provided up to three 24-hour dietary records every six months, in which detailed information on the commercial brands of consumed industrial foods was collected. Dietary exposure to food additives was estimated using comprehensive food composition databases and ad-hoc laboratory analyses in food matrices. Real-life data-driven mixtures of food additives were identified through Non-Negative Matrix Factorisation. Associations between time-dependent exposures to these mixtures and hypertension or CVD were assessed with multi-adjusted Cox models, and expressed as hazard ratios with 95% confidence intervals. Results Over a median follow-up of 7.92 years, 5,543, 2,450, 1,142 and 1,308 participants developed hypertension, CVD, CVA and CHD, respectively. Mixture 1 (mainly correlated with sodium carbonates, diphosphates, glycerol, ammonium carbonates) was associated with higher incidence of hypertension (HR tertile 3vs1 =1.14 [1.07–1.22]) and CVD (1.12 [1.00–1.24]); Mixture 2 (modified starches, pectin, guar gum, carrageenan) was associated with hypertension (1.12 [1.05–1.19]), CVD (1.18 [1.07–1.31]), and CHD (1.26 [1.10–1.45]); Mixture 4 (ammonium & sodium carbonates, diphosphates, α-tocopherol) was associated with higher incidence of hypertension (1.12 [1.05–1.19]), CVD (1.13 [1.02–1.26]), and CHD (1.16 [1.01–1.34]). Finally, Mixture 5 (citric acid, sodium citrates, phosphoric acid, acesulfame-K) was associated with an increased incidence of hypertension (1.19 [1.11–1.28]). No association was detected for Mixture 3 (magnesium carbonates, riboflavin, alpha-tocopherol, ammonium carbonates). Exploratory analyses revealed several interactions between emblematic additives composing mixtures, suggesting potential synergistic or antagonistic effects. Conclusions This study suggests a potential impact of food additive mixtures on cardiovascular and cerebrovascular health. Research is needed to explore underlying mechanisms. These findings call for mixture consideration in safety evaluations and support the recommendation of limiting unnecessary additives. Trial Registration This study is registered at ClinicalTrials.gov (NCT03335644, registered on November 2, 2017).