Preservative Food Additives and Cancer Incidence in the NutriNet-Santé Cohort

Abstract Background Experimental studies suggested negative impacts of some preservative food additives via mechanisms involving advanced glycation end products and mutagenic and potentially carcinogenic activities, but human data are lacking. This study aimed to investigate for the first time the associations between exposures to a wide range of preservative food additives and cancer incidence in a large population-based cohort. Methods Participants (n = 105,260; 78.7% women; mean age=42.0y SD = 14.5) from the French NutriNet-Santé prospective cohort (2009-2023) completed repeated 24h dietary records (mean=21 SD = 18), including industrial food brands. Cumulative time-dependent exposure to food additives was evaluated using multiple composition databases and ad hoc laboratory assays in food matrices. Associations between exposure to preservatives (3 categories: sex-specific tertiles or non-exposed/lower/higher exposed participants separated by the sex-specific median) and cancer incidence were characterised using proportional hazards Cox models adjusted for potential confounders. Results 4226 incident cancer cases were diagnosed (mean follow-up=7.57y; SD = 4.56) (incl. 1208 breast, 508 prostate, and 352 colorectal cancers). Higher intakes of the following additives were associated with higher cancer incidence: potassium sorbate with overall (Hazard Ratio (HR)cat3vs.1= 1.14[1.04-1.24]) and breast (1.26[1.07-1.49]) cancers; potassium metabisulphite with overall (1.11[1.03-1.20]), and breast (1.20[1.04-1.38]) cancers; sodium nitrite with prostate cancer (1.32[1.02-1.70]); potassium nitrate with overall (1.13[1.05-1.23]), and breast (1.22[1.05-1.41]) cancers; acetic acid with overall cancer (1.12[1.01-1.25]); and sodium erythorbate with overall (1.12[1.04-1.22]), and breast (1.21[1.04-1.41]) cancers. Conclusions This large prospective cohort revealed multiple positive associations between exposure to widely used preservatives and higher cancer incidence (overall, breast, prostate). Key messages • Six widely used food additive preservatives from industrial foods were associated with higher cancer incidence (overall, breast, prostate) in the NutriNet-Santé cohort (n = 105,260). • If confirmed, these new data could lead to a re-evaluation of the safety of these food additives by European and international public health agencies to improve consumer protection.