Nitrates or titanium dioxide may make you think of school chemistry lessons or fertilizers, rather than the food on your dinner plate. Ultra-processed food, such as savoury snacks, pre-packaged meals, sausages and certain breakfast cereals, have a long list of ingredients that are far from what grows in nature. 

“Such products, on average, have a lower nutritional quality and contain more salt and fat”, says Mathilde Touvier. “Most importantly, they are generally full of food additives such as sweeteners, dyes, or emulsifiers that help maintain a smooth texture and flavour.  Besides, the industrial process itself, sometimes with high temperatures, can produce toxic substances like acrylamide, acrolein and furan. “

Food intake

ADDITIVES seeks to understand the relationships between food additives and health risk. A main data source is the NutriNet-Santé cohort, which is the world’s biggest ongoing web-based study dedicated to the effect of dietary behaviours on health. Set up in 2009 in France, the cohort monitors the food intake of 173.000 adults through regular online dietary records. Participants note everything they eat or drink for 24 hours, in a food record that is then repeated three times at six-month intervals.

“We have collected very detailed information over a period of 13 years, not just about the quantities of a product participants have eaten but also of which brand”, Touvier says. “This is important because, depending on the brand, a chocolate cookie for instance may have very different compositions of food additives. Also, when we eat ultra-processed food, we do not just eat one type of artificial sweetener or other additive, but often mixtures that may have a synergistic or antagonistic interaction.”
 

Potential risks

The researchers found that those eating higher levels of ultra-processed foods had a higher risk of several chronic diseases. Food additives, explored in this project, are one of the main hypotheses to explain these associations. “No one escapes food additives but some people eat really higher amounts”, says Touvier. “In the study, we try not to influence what participants normally eat. Beyond dietary (and additives) exposures, we measured a wide range of potential confounding factors. People who eat more food additives may also do less physical activity, and perhaps smoke more. This was accounted for in our models. Subsequently, we are able to make correlations between these type of spontaneous dietary patterns and food additive exposures, and the incidence of chronic diseases during follow-up.”

The researchers’ discovery of an association between higher consumption of artificial sweeteners and an increased risk of cancer and cardiovascular diseases recently made news around the world.  They have also observed a link between exposure to nitrates and nitrites in processed meat and an increase risk of cancer, in particular breast and prostate cancers.

Touvier and her team cannot rule out that other unknown factors may have affected the results, which is typical of correlational studies on disease incidence. Touvier: “Methodologically, the ideal would be to complement these results with randomised controlled trials, but for ethical reasons this would of course not be possible since adverse effects are suspected. We cannot give some people a cocktail of additives and a placebo to another group and then see who dies first. So the evidence will have to rely on multiple observational studies as this one, and mechanistic data.”
 

Biological mechanism

In parallel to the observational studies, Touvier is studying the biological mechanisms underlying the association between additives and health, using experimental research conducted with partner teams. “We are transposing the exposure to these ‘cocktails’ of food additives observed in cohort participants to in vitro and animal models in the laboratory so we can study their impact on the gut barrier, on genotoxicity and on several other parameters that we are not able to test in real life.“

One hypothesis concerns emulsifiers, the chemical compounds used to mix incompatible processed food components. “Emulsifiers appear to allow toxic bacteria to invade protective mucus layers and enter the digestive system”, Touvier explains “This, in turn, causes inflammation in the abdomen as the body’s defences mobilise to destroy them. Emulsifiers may also disturb natural bacteria in the digestive system.”

The researchers will look at five biomarkers in blood and urine samples to get to grips with the exact impact of additives. “We will be able to see if the link between exposure to food additives and disease is mediated by an increase of inflammation”, says Touvier. “We will also perform metabolomic analysis, namely a laboratory test of several tens of metabolites simultaneously, to investigate potential perturbations of the metabolism associated with additive exposure.” Touvier and her team will also analyse faecal material to see if food additives are having an effect on ‘good’ natural bacteria in the digestive system, and are looking into oxidative stress and metabolic disturbance.

Safe products

ADDITIVES has a potential to generate important data that could be used as a basis to create evidence-based guidelines and legislative measures. Touvier argues for nuance in the debate. “There are more than 330 food additives authorised on the European market, and probably, many of them do not have an adverse effect. Therefore, not all substances should be treated in the same way. For public health, it is important to distinguish between additives that may have some adverse effect but are also beneficial for human health, for instance for food preservation or microbiological safety, and those additives that are potentially harmful and without any expected health benefit. If the food industry wants to make beautiful products, and uses inoffensive additives: why not, as long as consumer-safety comes first.”

Biography

Mathilde Touvier is a Research Director at the French National Institute for Health and Medical Research (INSERM) and the principal investigator of the NutriNet-Santé cohort. She is a graduate of AgroParisTech and Doctor in Epidemiology and Public Health. After six years at the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) and one year as a visiting researcher at Imperial College London, she joined the Nutritional Epidemiology Research Team EREN (INSERM / INRAE/ Cnam / Sorbonne Paris Nord University), of which she became Director in 2019. Touvier is member of the Scientific Council of the International Agency for Research on Cancer (WHO-IARC). She received the INSERM Research Prize in 2019 and a prize from the Bettencourt-Schueller Foundation in 2021. She has been appointed Professor at the College de France in Public Health for 2022-2023.