Food additives are widely used by the agri-food industry and are especially common in ultra-processed products found in supermarkets. Scientific research has linked the regular consumption of several of these additives to potential health issues, including metabolic disorders, chronic inflammation, and imbalances in the gut microbiome. Recent findings from the NutriNet-Santé cohort have also associated certain food additives with an increased risk of type 2 diabetes, cancer, and cardiovascular disease.

While previous studies have examined the effects of individual additives, none have looked at the potential health impact of consuming them in combination. This is important because ultra-processed foods often contain multiple additives with different functions, such as preservatives, colorants, flavor enhancers, and texture agents.

A Closer Look at 100,000+ Participants

To explore the possible effects of these additive mixtures, a research team led by Mathilde Touvier, research director at Inserm, analyzed health data from 108,643 adults in the NutriNet-Santé cohort, following participants for an average of 7.7 years.

The participants completed at least two days (up to 15 days) of online dietary records of all food and drinks consumed and their brands.

How Additive Mixtures Were Identified

In order to obtain a reliable estimate of the exposure to additives and to focus on those with a potentially significant health impact, only those additives consumed by at least 5% of the cohort were included in mixture modeling. The presence or absence of each additive in each food was determined by cross-referencing several databases, taking into account the date of consumption (to incorporate any reformulations over time), as well as some laboratory assays of quantitative levels of additives in the food.

Five main mixtures of additives were identified, representing groups of substances frequently ingested together (due to their joint presence in industrially processed products or resulting from the co-ingestion of foods often consumed together).

Two Mixtures Linked to Type 2 Diabetes

The results show two of these mixtures to be associated with a higher incidence of type 2 diabetes, regardless of the nutritional quality of the diet (intake of sugar, calories, fiber, saturated fat, etc.) and sociodemographic and lifestyle factors. No associations were found for the other three mixtures.

The first mixture incriminated was primarily composed of several emulsifiers (modified starches, pectin, guar gum, carrageenans, polyphosphates, xanthan gum), a preservative (potassium sorbate), and a coloring agent (curcumin). These additives are typically found in a variety of ultra-processed foods, such as stocks, milky desserts, fats, and sauces.

The Sweetened Drink Connection

The other mixture implicated was primarily composed of additives found in artificially sweetened drinks and sodas. It contained acidifiers and acidity regulators (citric acid, sodium citrates, phosphoric acid, malic acid), coloring agents (sulfite ammonia caramel, anthocyanins, paprika extract), sweeteners (acesulfame-K, aspartame, sucralose), emulsifiers (gum arabic, pectin, guar gum) and a coating agent (carnauba wax).

In this study, interactions between the additives of these mixtures were detected suggesting that some could interact with each other, either by enhancing their effects (synergy) or by attenuating them (antagonism).

A New Frontier in Diabetes Prevention?

“This study is the first to estimate exposure to food additive mixtures in a large cohort of the general population and to analyze their link to the incidence of type 2 diabetes. The findings suggest that several emblematic additives present in many products are often consumed together and that certain mixtures are associated with a higher risk of this disease. These substances may therefore represent a modifiable risk factor, paving the way for strategies to prevent type 2 diabetes,” explains Marie Payen de la Garanderie, PhD student at Inserm and first author of this research.

“Further studies are needed to elucidate the underlying mechanisms and deepen the understanding of the potential synergies and antagonisms between these substances. This observational study alone is not sufficient to establish a causal link. However, our findings are in line with recent in vitro experimental work suggesting possible cocktail effects.^[1] They indicate that the evaluation of additives should take into account their interactions and support public health recommendations that advise limiting non-essential food additives,” explains Dr. Touvier.

Notes

1. “Evaluation of the toxic effects of food additives, alone or in mixture, in four human cell models” by Cynthia Recoules, Mathilde Touvier, Fabrice Pierre and Marc Audebert, 14 December 2024, Food and Chemical Toxicology.
   DOI: 10.1016/j.fct.2024.115198

Reference: “Food additive mixtures and type 2 diabetes incidence: Results from the NutriNet-Santé prospective cohort” by Marie Payen de la Garanderie, Anaïs Hasenbohler, Nicolas Dechamp, Guillaume Javaux, Fabien Szabo de Edelenyi, Cédric Agaësse, Alexandre De Sa, Laurent Bourhis, Raphaël Porcher, Fabrice Pierre, Xavier Coumoul, Emmanuelle Kesse-Guyot, Benjamin Allès, Léopold K. Fezeu, Emmanuel Cosson, Sopio Tatulashvili, Inge Huybrechts, Serge Hercberg, Mélanie Deschasaux-Tanguy, Benoit Chassaing, Héloïse Rytter, Bernard Srour and Mathilde Touvier, 8 April 2025, PLOS Medicine.
DOI: 10.1371/journal.pmed.1004570

NutriNet-Santé is a public health study coordinated by the Nutritional Epidemiology Research Team (CRESS-EREN, Inserm/INRAE/Cnam/Sorbonne Paris Nord University/Paris Cité University) which, thanks to the commitment and loyalty of over 180 000 participants (known as Nutrinautes), advances research into the links between nutrition (diet, physical activity, nutritional status) and health. Launched in 2009, the study has already given rise to over 300 international scientific publications. In France, a drive to recruit new participants is still ongoing in order to continue to advance public research into the relationship between nutrition and health.

By devoting a few minutes per month to answering questionnaires on diet, physical activity, and health through the secure online platform etude-nutrinet-sante.fr, the participants contribute to furthering knowledge towards a healthier and more sustainable diet.