Diets have been shifting towards a dramatic increase in the consumption of ultra-processed foods (i.e. foods undergoing multiple physical, biological, and/or chemical processes and containing various food additives), while epidemiological evidence linking such consumption to adverse health outcomes is gradually accumulating as highlighted in more than 60 prospective studies worldwide. The NutriNet-Santé cohort in France was among the largest contributors to these results that emphasized the need of public health research on the topic. Food additives, substances added to foodstuffs for technological purposes (e.g. dyes, preservatives, emulsifiers, sweeteners), are a prime hypothesis to explain these results. Their use is widespread in industrially-processed foods, often containing a mixture of additives. As a result, millions of people daily ingest dozens of additives provided by multiple food products. While current evidence suggests that most additives found on the food market are likely to be neutral for health, concerning results of mainly in-vitro/in-vivo experimental studies have emerged regarding several compounds, used in hundreds of commonly consumed foods and beverages, such as TiO2, nitrates/nitrites, artificial sweeteners, phosphates, some emulsifiers, carrageenans, and glutamate, suggesting metabolic, gut microbiota and endocrine perturbations along with carcinogenic, inflammatory or oxidative stress effects. Despite the substantial work and collective expertise performed by health authorities to protect consumers against potential adverse effects of each substance in a given food product, their evaluation is based on the scientific evidence available to-date which is derived mainly from in-vitro and/or in-vivo toxicological studies and simulations of exposure in humans. Meanwhile, information regarding 1) the health impact of chronic and cumulative intake of food additives in humans, and 2) potential ‘cocktail’ effects (interactions) of multi-additive mixtures is still missing. In this context, the aims of ADDITIVES are to 1) estimate individual chronic exposure to food additives (as individual substances and as multi-additive mixtures), 2) investigate the relationships of additive exposure with risk of obesity, cancer, cardiovascular diseases, type 2 diabetes and mortality, 3) study biological mechanisms underlying those relationships, using a multi-disciplinary and multi-faceted approach.
