Exposure to food additive mixtures and type 2 diabetes risk in the NutriNet-Santé cohort

Abstract Background So far, the safety evaluation of food additives has been performed substance by substance, while in real life, millions of individuals are exposed to mixtures of food additives daily. According to preliminary experimental data, some of these chemicals, alone and/or in synergy are suspected to impact metabolic health. The objective of this study was to investigate for the first time the associations between exposure to mixtures of food additives and type 2 diabetes (T2D) risk in a large prospective cohort of French adults. Methods Participants (n = 108,783, 79.2% women, mean age=42.4 years, SD = 14.6) from the NutriNet-Santé cohort (2009-2024) completed repeated 24h-dietary records, detailing industrial product brands. Additive exposure was assessed using composition databases and laboratory assays. Five mixtures of additives were identified through non-negative matrix factorisation (NMF). Associations between these mixtures and the risk of T2D were characterised using multivariable proportional hazards Cox models adjusted for known risk factors. Findings 1115 participants were identified with T2D during follow-up. Two additive mixtures were associated with increased T2D risk. The first mixture included higher exposure to modified starches E14xx, pectins E440, guar gum E412, carrageenan E407, and polyphosphates E452 (HRper 1SD increment=1.11 [1.05-1.18]), p < 0.0001). The second mixture comprised citric acid E330, sodium citrates E331, phosphoric acid E338, sulphite ammonia caramel E150d, acesulfame-K E950, aspartame E951, sucralose E955 and arabic gum E414 (HR1SD=1.13 [1.08-1.18]), p < 0.0001). Interpretation This large prospective cohort study revealed direct associations between T2D risk and exposure to two food additive mixtures. Molecular epidemiology and experimental studies will be necessary to depict underlying mechanisms and potential cocktail effects. Key messages • Consumed together, widely used food additives may contribute to T2D aetiology, shedding light on the detrimental impact of highly processed foods on metabolic health. • This study highlights positives associations between T2D risk and exposure to two food additive mixtures.