© Mathilde Touvier

Food additive mixtures are an everyday feature of our diets, especially through ultra-processed foods. Until recently, safety evaluations of these additives have been conducted substance by substance due to a lack of data on the effect of them ingested together. In a new study, researchers from Inserm, INRAE, Sorbonne Paris Nord University, Paris Cité University and Cnam, as part of the Nutritional Epidemiology Research Team (CRESS-EREN), examined the possible links between exposure to mixtures of commonly consumed food additives and the onset of type 2 diabetes. They analysed the health data of over 100 000 adults participating in the French NutriNet-Santé cohort. Two out of the five mixtures tested were found to be associated with a higher incidence of type 2 diabetes, particularly one mixture containing different emulsifiers such as carrageenans, modified starches and other additives (found in stocks, milky desserts, fats and sauces, etc.), and another containing sweeteners, colourings and acidifiers (characteristic of artificially-sweetened drinks and sodas). Their findings have been published in Plos Medicine.

Widely used by the agri-food industry, food additives are mainly found in the ultra-processed products sold in our supermarkets. The scientific literature now provides information on the potential harmful effects of consuming several of these substances, which have been associated with the development of metabolic disorders, chronic inflammation and gut microbiome imbalance. Recent studies from the NutriNet-Santé cohort have also revealed an association between the consumption of some of these additives and an increased risk of type 2 diabetes, cancer and cardiovascular diseases.

Although these studies provide insights into the individual effect of each of these substances, no study had yet looked at the possible impact of their combined consumption. And this is despite ultra-processed foods often containing mixtures of food additives, each with its specific properties (preservatives, flavour enhancers, colourants, texture agents, etc.).

To measure the consequences of exposure to these mixtures, a research team led by Mathilde Touvier, Inserm research director and study coordinator, analysed the health data of 108 643 adults in the NutriNet-Santé cohort over an average follow-up period of 7.7 years.

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

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 modelling. 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).

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, fibre, 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 colouring agent (curcumin). These additives are typically found in a variety of ultra-processed foods, such as stocks, milky desserts, fats and sauces.

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), colouring agents (sulphite 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).

“This study is the first to estimate exposure to food additive mixtures in a large cohort of the general population and to analyse 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.

[1] Cynthia Recoules, Mathilde Touvier, Fabrice Pierre, Marc Audebert. Food Chem Toxicol. 2025 Feb:196:115198. doi: 10.1016/j.fct.2024.115198. Epub 2024 Dec 14. Evaluation of the toxic effects of food additives, alone or in mixture, in four human cell models.

© AdobeStock

Human cognitive biases can particularly affect decision-making when speed is of the essence, such as when lives are at stake in a medical emergency. A research team from Inserm and the University of Bordeaux has tested an advanced method of generative artificial intelligence (AI)[1], trained with data from patient records corresponding to 480 000 entries to the Bordeaux University Hospital Emergency Department. Its findings, presented at the Machine Learning for Health symposium in Vancouver, and published in Proceedings of Machine Learning Research, show that the AI tested is likely to reproduce and measure caregiver biases relating to patient gender during triage. These results form a case study of how new generative AI algorithms can be used to identify and understand human cognitive biases.

In emergency care settings that demand rapid decision-making, human cognitive biases, particularly “judgment” biases, can critically impact medical decisions and patient prognosis. These “cognitive shortcuts” occur when people are required to form opinions or make decisions based on incomplete or over-generalized information. Decision-making can therefore be unconsciously affected by these biases (related, for example, to sex/gender, age, ethnicity, etc.), and lead to under or overestimating the severity of a patient’s condition.

So how can we better identify these biases and reduce their impact? One answer could be found in AI and particularly generative AI known as “large language models” (LLMs), which are capable of imitating human decision-making thanks to their mastery of human language (such as ChatGPT). These models are in fact capable of effectively understanding the “free-text”[2] that accounts for a large proportion of the clinical data collected by healthcare staff, particularly in hospital emergency departments.

A team led by Inserm Research Director Emmanuel Lagarde[3] at the Bordeaux Population Health Research Center (Inserm/University of Bordeaux), was interested in the potential of these LLMs to detect and quantify gender bias in a rapid decision-making setting. The context used to evaluate this method was the triage[4] of patients in emergency departments. Accurate triage is critical: underestimating an emergency in which treatment is then delayed could worsen prognosis. However, overestimating the severity of a patient’s condition could lead to the overuse of resources, which can be particularly harmful if many other patients are also requiring attention.

The scientists used an innovative approach in which AI was trained to triage patients based on the texts contained in their medical record, thereby reproducing any cognitive biases of the nursing staff having performed this triage. The data used for this training comprised over 480 000 entries to the Emergency Department of Bordeaux University Hospital between January 2013 and December 2021.

Once trained, the model was capable of assigning a triage score (evaluating the severity of the patient’s condition) based on reading a record, as the nurse would do. The record was then altered in order to change patient gender references in the clinical texts, and a new score was assigned by the model. It was the difference between these two scores, one produced from the original record and the other from the altered record, which made it possible to estimate the cognitive bias.

The results showed the AI to be significantly biased against women. Based on identical clinical records, the severity of their conditions tended to be underestimated compared to those of men (with around 5% classified as “less critical” and 1.81% classified as “more critical”). Conversely, the severity of the men’s conditions tended to be slightly overestimated (with 3.7% deemed “more critical” versus 2.9% deemed “less critical”). This bias increased in line with the level of inexperience of the nursing staff.

“This research shows how large language models can help detect and anticipate human cognitive biases – in this case regarding the goal of fairer and more effective management of medical emergencies,” explains Lagarde. “The method used shows that, in this context, LLMs are able to identify and reproduce the biases that guide human decision-making from the clinical data collected by nursing staff,” adds Ariel Guerra-Adames, doctoral student and first author of this research[5].

The team will now go on to study the evaluation of biases related to other patient characteristics (age, ethnic group). Ultimately, it should also be possible to refine the system with the introduction of non-verbal variables (facial expressions, tone of voice) which, while not necessarily appearing in the written data, could nevertheless be critical in decision-making.

[1] Generative artificial intelligence is an AI system that is able to create content, be it text, images, sounds, videos or other forms of data.

[2] In a medical context, free-text refers to information recorded as unstructured text, i.e. without rigid organization or a predefined format. This includes texts produced directly by healthcare professionals to describe observations, diagnoses, treatments or medical history, often in natural language.

[3] In collaboration with Cédric Gil-Jardiné from the University of Bordeaux Hospital Emergency Department and Marta Avalos from the Inria center at the University of Bordeaux

[4] Triage in medical emergencies consists of classifying patients by the severity of their condition, so as to optimize the order of care and save as many people as possible. It is performed by dedicated nurses who collect various information from each patient (reason for visit, vital signs, medical history, etc.) and assign an “emergency” score according to a validated scale.

[5] Ariel Guerra-Adames received the Best Paper Award when presenting this work at the Machine Learning for Health Symposium in Vancouver.

L’alimentation serait responsable d’environ 30% des décès dus aux maladies cardiovasculaires. © Mathilde Touvier

Cardiovascular diseases are the leading cause of mortality in Western Europe, accounting for 1/3 of deaths in 2019. Diet is thought to be responsible for around 30% of such deaths. Nutrition-related prevention policies therefore constitute a major public health challenge for these diseases.

In an article to be published on 11 September 2024 in Lancet Regional Health – Europe, researchers from the Nutritional Epidemiology Research Team (CRESS-EREN), with members from Inserm, Inrae, Cnam, Université Sorbonne Paris Nord and Université Paris Cité, in collaboration with researchers from the International Agency for Research on Cancer (WHO-IARC), report an increased risk of cardiovascular diseases associated with the consumption of foods that rank less favourably on the Nutri-Score scale (new 2024 version) within the European cohort EPIC. A total of 345,533 participants from the cohort, spread across 7 European countries and followed for 12 years, were included in the analyses.

Officially adopted in France in 2017 (and in 6 other European countries since), the Nutri-Score aims to provide rapid information on the nutritional quality of foods and drinks to help and encourage consumers to compare them and choose those that offer a better nutritional quality. In parallel, it encourages manufacturers to improve the nutritional quality of their products.

The Nutri-Score has 5 categories, ranging from A (dark green – higher nutritional quality) to E (dark orange – lower nutritional quality). An algorithm ranks each product according to its levels – per 100 g – of energy, sugars, saturated fatty acids and salt (to limit) and proteins, fruits, vegetables and pulses (to favour).

A number of studies published in international scientific journals have shown the validity of Nutri-Score in characterising the nutritional quality of foods and its efficacy in guiding consumers towards more nutritious choices (over 140 publications). In particular, links between the consumption of foods with a less favourable Nutri-Score (lower nutritional quality) and an increased risk of cardiovascular diseases have so far been observed in French studies (SU.VI.MAX and NutriNet-Santé cohorts). Studies in France, UK, Spain and Italy have also seen similar associations with an increased risk of various chronic diseases as well as higher mortality.

In this new study, the researchers focused on the latest version of the Nutri-Score algorithm (updated in 2024, see box), linked to the risk of cardiovascular diseases, in a large population spread across 7 European countries, with the aim of providing new scientific evidence for validating the Nutri-Score on a European scale. It follows two studies published in 2018 and 2020 in the same population on cancer risk and mortality.

A total of 345 533 participants from the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort were included in the analyses. During the follow-up (12 years, between 1992 and 2010), 16 214 participants developed a cardiovascular disease (6 565 of whom had myocardial infarction and 6 245 stroke). The findings show that the participants consuming on average more foods with less favourable Nutri-Score, reflecting lower nutritional quality, were at increased risk of cardiovascular diseases, particularly myocardial infarction and stroke. These associations were significant after a large number of sociodemographic and lifestyle factors were taken into account.

‘These findings confirm the relevance of Nutri-Score as a public health tool to guide consumers in their food choices with the goal of preventing chronic diseases’, emphasises Inserm researcher Mélanie Deschasaux-Tanguy.

‘They also provide key elements to support the adoption of Nutri-Score as a mandatory nutritional logo in Europe’, explains Mathilde Touvier, Inserm research director.

 

[1] https://sante.gouv.fr/prevention-en-sante/preserver-sa-sante/nutrition/nutri-score/etudes-et-rapports-scientifiques/

[2] https://theconversation.com/en-2024-le-nutri-score-evolue-pourquoi-et-que-faut-il-en-retenir-221697

To find out more: watch the Inserm program “Nutri-Score, we tell you everything” (french only).

© Julie Borgese

Inserm has published a new Collective Expert Review on the theme of multiple disabilities, commissioned by the French National Solidarity Fund for Autonomy (CNSA). During the 3 years it took to prepare it, a group of 12 experts reviewed over 3400 documents from the international scientific literature available as at the second half of 2023. The conclusions and recommendations of this Collective Expert Review provide useful new elements to improve care and help answer questions regarding the consideration, interactions and integration of people with multiple disabilities.

The term ‘multiple disabilities’ refers to the permanent consequences of a lesion (genetic or accidental) that occurs during the brain’s development and results in severe motor impairment and intellectual disability evaluated as severe to profound. Multiple disabilities are associated not just with extremely restricted communication, autonomy and mobility, but also with comorbidities, sensory impairment and behavioural disorders.

In France, the prevalence of multiple disabilities is currently estimated at around 0.3-0.5 people in every 1000.

Complex clinical care

The situations caused by multiple disabilities differ greatly from one person to another, with many disorders that are interlinked. Each must be taken into account when setting up care.

For example, epilepsy, which is very common, presents as a veritable secondary disability. As for respiratory disorders, they constitute the leading cause of mortality and emergency hospitalisation among people with multiple disabilities.

Other disorders that are commonly encountered include:

• difficulty feeding oneself, digestive and nutritional disorders;
• due to very limited mobility, bone fragility in children and osteoporosis in adults, excessively weak muscle tone, posture defects and orthopaedic deformities (scoliosis, hip dislocation, etc.);
• frequent sleep disorders in children (significantly impacting the quality of life of those around them);
• disruptions to puberty (late or early).

Pain, often multifactorial, is common, sometimes chronic from an early age, and rarely expressed through the usual modes of communication (such as verbal complaints). This makes it difficult to evaluate, leading to the risk of underestimating it. Generally dependent on a third party (healthcare professional or caregiver), such evaluation therefore raises ethical and methodological questions.

The expert group recommends:

• for motor disorders: rehabilitation via adapted interventions aimed at promoting voluntary movements and motor learning; on a daily basis, prevention of the consequences of impaired motor activity by reducing passive activities (watching television for example) in favour of movement-based activities;
• for intellectual disability: promotion of interaction-generating environments for people with multiple disabilities and their integration into everyday social spaces, with the appropriate conditions and trained personnel. An appropriate and soothing environment makes it possible to improve the common behavioural disorders (self-aggression, repetitive behaviours, etc.) that are largely linked to living environment;
• for pain: systematically screen for its presence, evaluate its intensity, frequency and duration using specific validated tools and search for its cause(s) using a detailed examination;

more globally: generalise validated methods for evaluating quality of life, combining different objective approaches in a complementary manner (evaluations by medical staff, parents and other people close to the patient) and self-evaluation.

A French cohort of children and adults with multiple disabilities (Eval-PLH) is ongoing. Future data will make it possible to evaluate, for example, the mortality rate and causes of death of people with multiple disabilities.

Support and social integration of people with multiple disabilities

Alongside medical care, multiple disabilities involve lifelong comprehensive and individualised support, in order to offer people a life plan that is appropriate to their various needs and their personal development pathway. Evaluation of the skills, difficulties (medical, psychological, interpersonal) and methods of communication of people with multiple disabilities must be carried out regularly.

This support is crucial in terms of educational and social aspects, particularly for the core subject of being able to communicate, but also for learning, schooling, inclusion and social participation. People with multiple disabilities have the possibility to learn throughout their lives if the right arrangements are made. Some skills, if stimulated in early childhood, improve socialisation and communication over the long term. In addition, people with multiple disabilities can participate in various activities of daily and social life thanks to certain aids, methods and tools that make their environment more suitable.

The expert group recommends:

• using the severity rating scale for multiple disabilities, validated in French to evaluate individual skills and difficulties;
• enabling children with multiple disabilities to have access to education tailored to their needs and enabling them to develop their capacities to the fullest;
• reflecting on the types of learning that benefit children with multiple disabilities in order to build a ‘tailored’ educational pathway within teaching units involving teams from both specialised institutions and ordinary schools;
• implementing a combination of several modes of communication (voice, touch, gaze, gestures, etc.) and Augmentative and Alternative Communication (AAC) individually adapted to the person’s motor and cognitive abilities and enabling both communication and mutual understanding – this may be a succession of gestures (for example, inspired by sign language) or objects with a precise meaning, but also technological means.

The central roles of those close to people with multiple disabilities

Because of their dependence and extreme physical and psychological vulnerability, people with multiple disabilities need a high level of care and attention. The family, other people close to them and professionals are therefore highly impacted on the practical (care, day-to-day organisation) and emotional levels and play a prominent role in support. The evaluation of needs, their coordinated implementation and their adaptation to advancing age demand a multidisciplinary approach and complex coordination between carers.

While the French system (care for people with multiple disabilities, approval of reference and competence centres for multiple disabilities of rare causes) is likely to meet the various life-long needs of the people concerned, the coordination and continuity of the care pathway is not always optimal.

Thus the transition to adulthood, a continuous process that starts between 13 and 15 years of age, remains difficult with medical, social and legal implications for the individual and their family. The severity of multiple disabilities grows with age, consequently increasing the level of dependence. The end of life of people with multiple disabilities also raises many challenges relating to ethics and resources.

Intimacy and affectivity are essential for someone who is in a situation of total physical dependence and without a unified perception of their body. Affection and attention therefore play a decisive role in care and learning.

When it applies to someone whose mental life and psychological and emotional development develop in an atypical way, the question of sexuality finds itself confronted against communication problems and ethical questions.

Finally, in a context where the person is entirely dependent on the interpretations of their communication partners, the high level of vulnerability – physical, psychological and communicational – which characterises multiple disabilities reinforces the risks of abuse (voluntary or involuntary), which can accumulate.

The expert group recommends:

• conducting early identification and diagnosis of multiple disabilities in children, involving families from the outset and providing adequate support;
• offering early interventions while promoting care in inclusive early childhood environments in partnership with specialised services;
• to prevent institutional abuse, the establishment of practice analysis groups, solid ongoing training, a culture of well-treatment and a monitoring unit in institutions and departments. However, the experts warn that these measures cannot replace sufficient human resources with the appropriate equipment;
• to prevent parental abuse, take into account the psychological suffering of parents and encourage pair work and group- and multidisciplinary exchanges. Patient organisations and social media discussion groups are ways of limiting the effects of social exclusion, especially for parents forced to give up work;
• to guard against forms of involuntary or passive abuse (laissez-faire, negligence, lack of knowledge, etc.) that may be linked to inappropriate care, interpersonal habits likely to intensify communicational vulnerability, or even an underestimation of the person’s cognitive abilities that may lead to a negation of their psychological life;
• to recognise and take into account the person’s manifestations of sexuality, to question what the modes of this sexuality may be; to not neglect emotional life by clearly distinguishing it from the questions of sexuality.

Embryo obtained after in vitro fertilisation (five days after in vitro fertilisation and culture). © Prof. P. Fauque, Dijon University Hospital

Inserm scientists from the Epidemiology of Childhood and Adolescent Cancers team (EPICEA – Inserm JRU 1153)[1] and the EPI-PHARE scientific interest group (ANSM/Cnam), together with experts in medically assisted reproduction (MAR), have published in JAMA Network Open the findings of a large-scale study aimed at comparing the risk of cancer in children conceived by MAR with that of children conceived naturally. Involving over 8.5 million children born in France between 2010 and 2021, this is one of the largest studies conducted to date on the risk of cancer in children conceived by MAR.

Although the study does not show an increased overall risk of cancer among children born after MAR, it does suggest a very slight increase in their risk of leukaemia.

MAR concerns approximately 1 in 30 births in France (see box). The available data, which remain limited and heterogeneous, have suggested increased risks of certain health conditions, including cancers, among children conceived through it. Large-scale evaluation of the cancer risk is essential and constitutes a priority research objective, as a recent report from the French National Academy of Medicine shows[2].

Scientists from Inserm and EPI-PHARE, in conjunction with specialists in MAR, evaluated this cancer risk in one of the world’s largest cohorts of children born after MAR.

They used data from the French National Health Data System (SNDS)[3] to identify children conceived by MAR (artificial insemination, conventional in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI)) and to detect the onset of cancer in children conceived with or without the use of MAR.

All in all, the study concerned the 8 526 306 children born in France between 2010 and 2021, of whom 260 236 (3%) were conceived by MAR, and followed them up to a median age of 6.7 years.

During this follow-up, 9 256 children, including 292 conceived by MAR, developed cancer. The overall risk of cancer was no higher in the children conceived by MAR than in those conceived naturally.

However, a slight increase in leukaemia risk was observed in the children conceived by IVF or ICSI. This increase is very small – representing one additional case per 5 000 newborns conceived by IVF or ICSI having reached 10 years of age – and requires confirmation.

While the absence of an increased overall risk of cancer is reassuring, the epidemiological monitoring will be continued in order to better evaluate the cancer risk over the longer term. It is also necessary to continue research efforts in order to understand which mechanisms related to MAR techniques or parental fertility disorders could induce the increased risk of leukaemia, should this be confirmed.

This study received funding from the ANSM.

[1] The team is based at the Centre for Research in Epidemiology and Statistics – CRESS (Inserm/Université Paris Cité).

[2] Jouannet P, Claris O, Le Bouc Y. Rapport 23-07. Santé à moyen et à long terme des enfants conçus par fécondation in vitro (FIV). Bull Acad Ntle Med 2023; 207: 695-705.

[3] The SNDS, which groups France’s main existing public health databases, aims to improve knowledge of medical care and broaden the scope of research, studies and evaluations in the field of health.

Emulsifiers are among the most commonly used additives. They are often added to processed and packaged foods such as certain industrial cakes, biscuits and desserts, as well as yoghurts, ice creams… © Kenta Kikuchi sur Unsplash

Emulsifiers are among the additives most widely used by the food industry, helping to improve the texture of food products and extend their shelf life. Researchers from Inserm, INRAE, Université Sorbonne Paris Nord, Université Paris Cité and Cnam, as part of the Nutritional Epidemiology Research Team (CRESS-EREN), studied the possible links between the dietary intake of food additive emulsifiers and the onset of type 2 diabetes between 2009 and 2023. They analysed the dietary and health data of 104 139 adults participating in the French NutriNet-Santé cohort study, specifically evaluating their consumption of this type of food additive using dietary surveys conducted every six months. The findings suggest an association between the chronic consumption of certain emulsifier additives and a higher risk of diabetes. The study is published in Lancet Diabetes & Endocrinology.

In Europe and North America, 30 to 60% of dietary energy intake in adults comes from ultra-processed foods. An increasing number of epidemiological studies suggest a link between higher consumption levels of ultra-processed foods with higher risks of diabetes and other metabolic disorders.

Emulsifiers are among the most commonly used additives. They are often added to processed and packaged foods such as certain industrial cakes, biscuits and desserts, as well as yoghurts, ice creams, chocolate bars, industrial breads, margarines and ready-to-eat or ready-to-heat meals, in order to improve their appearance, taste and texture and lengthen shelf life. These emulsifiers include for instance mono- and diglycerides of fatty acids, carrageenans, modified starches, lecithins, phosphates, celluloses, gums and pectins.

As with all food additives, the safety of emulsifiers had been previously evaluated by food safety and health agencies based on the scientific evidence that was available at the time of their evaluation. However, some recent studies suggest that emulsifiers may disrupt the gut microbiota and increase the risk of inflammation and metabolic disruption, potentially leading to insulin resistance and the development of diabetes.

For more information: read Inserm’s report on type 2 diabetes

For the first time worldwide, a team of researchers in France has studied the relationships between the dietary intakes of emulsifiers, assessed over a follow-up period of maximum 14 years, and the risk of developing type 2 diabetes in a large study in the general population.

The results are based on the analysis of data from 104 139 adults in France (average age 43 years; 79% women) who participated in the NutriNet-Santé web-cohort study (see box below) between 2009 and 2023.

The participants completed at least two days of dietary records, collecting detailed information on all foods and drinks consumed and their commercial brands (in the case of industrial products). These dietary records were repeated every six months for 14 years, and were matched against databases in order to identify the presence and amount of food additives (including emulsifiers) in the products consumed. Laboratory assays were also performed in order to provide quantitative data. This allowed a measurement of chronic exposure to these emulsifiers over time.

During follow-up, participants reported the development of diabetes (1056 cases diagnosed), and reports were validated using a multi-source strategy (including data on diabetes medication use). Several well-known risk factors for diabetes, including age, sex, weight (BMI), educational level, family history, smoking, alcohol and levels of physical activity, as well as the overall nutritional quality of the diet (including sugar intake) were taken into account in the analysis.

After an average follow-up of seven years, the researchers observed that chronic exposure – evaluated by repeated data – to the following emulsifiers was associated with an increased risk of type 2 diabetes:

• carrageenans (total carrageenans and E407; 3% increased risk per increment of 100 mg per day)
• tripotassium phosphate (E340; 15% increased risk per increment of 500 mg per day)
• mono- and diacetyltartaric acid esters of mono- and diglycerides of fatty acids (E472e; 4% increased risk per increment of 100 mg per day)
• sodium citrate (E331; 4% increased risk per increment of 500 mg per day)
• guar gum (E412; 11% increased risk per increment of 500 mg per day)
• gum arabic (E414; 3% increased risk per increment of 1000 mg per day)
• xanthan gum (E415; 8% increased risk per increment of 500 mg per day)

This study constitutes an initial exploration of these relationships, and further investigations are now needed to establish causal links. The researchers mentioned several limitations of their study, such as the predominance of women in the sample, a higher level of education than the general population, and generally more health-promoting behaviours among the NutriNet-Santé study participants. Therefore caution is needed when extrapolating the conclusions to the entire French population.

The study is nevertheless based on a large sample size, and the researchers have accounted for a large number of factors that could have led to confounding bias. They also used unique, detailed data on exposure to food additives, down to the commercial brand name of the industrial products consumed. In addition, the results remain consistent through various sensitivity analyses[1], which reinforces their reliability.

‘These findings are issued from a single observational study for the moment, and cannot be used on their own to establish a causal relationship. They need to be replicated in other epidemiological studies worldwide, and supplemented with toxicological and interventional experimental studies, to further inform the mechanisms linking these food additive emulsifiers and the onset of type 2 diabetes. However, our results represent key elements to enrich the debate on re-evaluating the regulations around the use of additives in the food industry, in order to better protect consumers,’ explain Mathilde Touvier, Research Director at Inserm, and Bernard Srour, Junior Professor at INRAE, lead authors of the study.

Among the next steps, the research team will be looking at variations in certain blood markers and the gut microbiota linked to the consumption of these additives, to better understand the underlying mechanisms. The researchers will also look at the health impact of additive mixtures and their potential ‘cocktail effects.’ They will also work in collaboration with toxicologists to test the impact of these exposures in in vitro and in vivo experiments, to gather more arguments in favour of a causal link.

[1] Sensitivity analyses in epidemiology aim to test the robustness of statistical models by varying certain parameters, hypotheses or variables in the model to assess the stability of the associations observed. For example, in this study, additional account was taken of sweetener consumption, weight gain during follow-up and other metabolic diseases.

A new study provides an overview of the health of French citizens just prior to the 2019 pandemic and its evolution from 1990 to 2019 © Unsplash

In order to implement suitable public health policies, it is crucial to know the health status of the population and its evolution over time. This knowledge is all the more important given the severe disruptions caused by the COVID-19 pandemic to healthcare systems worldwide. For the first time, a study by teams from Inserm, Université de Bordeaux and Bordeaux University Hospital in collaboration with Santé publique France, French National Health Insurance (CNAM) and the Global Burden of Disease (GBD) study collaborators, provides an overview of the health of French citizens just prior to the 2019 pandemic, and its evolution from 1990 to 2019. This research also compares the French situation with that of other European countries, resulting in an accurate assessment to guide public decision-making and reflect on the more general impact of COVID-19 on French health. The study findings have been published in The Lancet Regional Health.

The COVID-19 pandemic has disrupted the organisation of healthcare systems and exacerbated problems that many countries, including France, were already facing, such as inequalities in healthcare access, hospital pressures and shortages of healthcare professionals. In order to address these challenges beyond the usual surveillance systems, it is essential to make a more accurate diagnosis of the health of French citizens prior to the COVID-19 crisis, particularly in an attempt to analyse its specific impact on different health indicators.

This is the proposal of a new study by teams from Inserm, Université de Bordeaux and Bordeaux University Hospital, in collaboration with Santé publique France and French National Health Insurance (CNAM). This study evaluated several French health indicators in 2019 prior to the pandemic, as well as their evolution from 1990 to 2019, and offers a comparison of France’s situation with that of other Western European countries over the same period.

The added value of GBD data

The Global Burden of Disease (GBD) study, coordinated by the Institute for Health Metrics and Evaluation, has been conducted since 1990 by a global network of 5,647 employees across 152 countries and territories. The 2019 study analyses 286 causes of death, 369 diseases and injuries, and 87 risk factors in 204 countries and territories. GBD has been used to inform health policies in many nations and local jurisdictions, as well as by international organisations such as the World Bank and World Health Organization.

However, this wealth of data had never previously been used and presented specifically for France to describe the health evolution of its citizens through indicators reflecting sociodemographic status, life expectancy, healthy life expectancy and years lived with disability.

Improved life expectancy and healthy life expectancy

The results of the analysis confirm that over the period considered (1990 to 2019), life expectancy at birth in France had improved over time, from 77.2 years in 1990 to 82.9 years in 2019, ranking it seventh in terms of life expectancy among the 23 western European countries studied. What is more, the French live longer in good health on average, with their healthy life expectancy having also increased – this time from 67 to 71.5 years, and placing the country in fourth position.

The increase in healthy life expectancy makes it possible to hypothesise on the improvements made in certain areas, such as better care or more appropriate prevention, thereby limiting the development of diseases. This study thus makes it possible to estimate the burden of diseases according to their impact on the various GBD indicators.

Compared to other European countries, cardiovascular diseases play a smaller role in morbidity and mortality in France.

‘We have observed that the stroke and ischaemic heart disease burden is lower in France than in other Western European countries. This finding, which has been seen in the past, could be explained by a lower prevalence of many cardiovascular risk factors (hypertension, diabetes) and a healthier lifestyle (exercise, diet) in France. Efforts must continue to be made to prevent and treat these diseases, whose prevalence nevertheless continues to remain high,’ explain the authors.

It is also important to provide better care for mental health disorders (particularly depressive- and anxiety disorders) and musculoskeletal disorders (particularly low back pain) which represent the main reasons for years lived with disability.

The study also highlights the progress that needs to be made in preventing cancer, particularly by continuing efforts to combat smoking. In France, as in other European countries, cancer is still the leading cause of mortality.

‘Overall, these findings highlight a marked trend towards the improvement of health in France. They should encourage decision-makers to design intervention strategies to reduce the burden of morbidity and mortality, paying particular attention to causes such as cancer, cardiovascular diseases, mental health and musculoskeletal disorders,’ the authors point out.

This study is therefore a valuable resource, complementing the regular epidemiological surveillance conducted by Santé publique France in particular, to guide public policies and implement relevant measures to improve prevention initiatives and access to healthcare. It is also an important first step towards improving our understanding of the impact of the COVID-19 pandemic on the health of French people. The same study will now have to be carried out with the data collected at the end of the health crisis on these same key indicators, in order to highlight any changes in the population’s health.

© Mathilde Touvier/Inserm

Emulsifiers are among the additives most widely used by the food industry, helping to improve the texture of food and extend its shelf life. Researchers from Inserm, INRAE, Université Sorbonne Paris Nord, Université Paris Cité and Cnam, as part of the Nutritional Epidemiology Research Team (CRESS-EREN), have undertaken to study the possible links between the dietary intake of food additive emulsifiers and the development of cancer. They analysed the health data of 92 000 adults participating in the French NutriNet-Santé cohort study, specifically evaluating their consumption of this type of food additive. The results of this research, published in PLoS Medicine, suggest an association between the intake of certain emulsifiers and an increased risk of cancer – particularly of the breast and prostate.

In Europe and North America, 30 to 60% of dietary energy intake in adults comes from ultra-processed foods. An increasing number of epidemiological studies suggest a link between high intakes of ultra-processed foods with higher risks of obesity, cardiometabolic diseases and certain forms of cancer.

Emulsifiers are among the most commonly used additives in these foods. They are often added to processed and packaged foods such as certain industrial cakes, biscuits and desserts, as well as ice creams, chocolate bars, breads, margarines and ready meals, in order to improve their appearance, taste and texture and lengthen shelf life. These include mono- and diglycerides of fatty acids, carrageenans, modified starches, lecithins, phosphates, celluloses, gums and pectins.

As with all food additives, the safety of emulsifiers had already been evaluated based on the scientific evidence available at the time. However, some recent studies suggest that emulsifiers may disrupt the gut microbiota and increase the risk of inflammation, potentially increasing susceptibility to some types of cancer. For the first time at an international level, a team of French researchers has studied the relationships between the dietary intake of emulsifiers and the risk of several forms of cancer in a large study in the general population.

The results are based on the analysis of data from 92 000 adults in France (average age 45 years; 79% women) who participated in the NutriNet-Santé cohort study (see box below) between 2009 and 2021.

The participants completed at least 3 days of online dietary records of all food and drink consumed and their brand (for industrial products), with the possibility of updating their dietary intake data every 6 months. These records were matched against databases in order to identify the presence and level of food additives (including emulsifiers) in the products consumed. Laboratory assays were also performed in order to provide quantitative data.

During the follow-up, the participants reported the onset of any cancer (2 604 cases diagnosed), which was validated by a medical committee following examination of their medical records. Several well-known risk factors for cancer, including age, sex, weight (BMI), educational level, family history, smoking, alcohol and levels of physical activity, as well as the overall nutritional quality of the diet (e.g. sugar, salt, energy intakes) and menopausal status were taken into account.

After an average follow-up of 7 years, the researchers found that higher intakes of mono- and diglycerides of fatty acids (E471) were associated with increased risks of cancer overall (a 15% higher risk among those consuming the most – 3rd tertile – compared with those consuming the least – 1st tertile), breast cancer (a 24% higher risk), and prostate cancer (a 46% higher risk). On the other hand, women with higher carrageenan intakes (E407 and E407a) had a 32% higher risk of developing breast cancer, compared with the group with lower intakes.

Given that this is the first observational study in this area, it cannot establish causality on its own, and the authors acknowledge it to have certain limitations. For example, the high proportion of women, the higher average level of education and the generally more health-conscious behaviours among the NutriNet-Santé study participants compared with the general French population, which may limit the generalisation of the results

That being said, the study sample was large and the authors were able to consider a wide range of potentially confounding factors, while using detailed and unique data on exposures to food additives, down to the brand of the products consumed. In addition, the results remained unchanged after multiple sensitivity analyses, thereby strengthening their robustness.

‘While these findings need to be replicated in other studies worldwide, they bring new key knowledge to the debate on re-evaluating the regulations around the use of additives in the food industry, in order to better protect consumers,’ explains Mathilde Touvier, Research Director at Inserm, and Bernard Srour, Junior Professor at INRAE, lead authors of the study.

 

ADHD manifests as high levels of inattention and/or hyperactivity and impulsivity. © Adobe Stock

Attention-deficit hyperactivity disorder (ADHD) affects many children and is often accompanied by other conditions, such as metabolic disorders, asthma and dental caries. However, uncertainties remain as to the chronology of onset of such conditions, particularly when it comes to knowing which are linked with ADHD over time or, on the other hand, which increase the risk of developing ADHD symptoms. Scientists from Inserm and Université de Bordeaux at the Bordeaux Population Health Center in collaboration with teams in the UK, Sweden and Canada have conducted the most comprehensive analysis to date by evaluating temporal links between ADHD symptoms and a wide range of medical conditions. Their findings, published in Lancet Child and Adolescent Health, highlight the importance of the multidisciplinary management of ADHD patients, based on enhanced collaboration between physical and mental healthcare professionals.

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that begins in childhood and is characterised by high levels of inattention and/or hyperactivity and impulsivity. In addition to the difficulties it causes at school and in professional and social life, research has shown that ADHD is associated with various medical comorbidities (metabolic disorders, asthma, obesity, addictions, etc.) and an increased risk of accidental injury.

Nevertheless, the studies published so far in this area presented methodological limitations. With their small patient samples and lack of long-term health follow-up, they were unable to determine the direction of the links observed and the chronology of their onset. In addition, confounding factors such as social health inequalities or medication use were often insufficiently taken into account.

This made it difficult for scientists to answer a certain number of questions: do comorbidities appear before or after the development of ADHD? Are they directly related to it or caused by other factors? Can ADHD be promoted by previous medical conditions? Yet it is understanding the temporal sequences of these different associations that is essential in order to develop appropriate care and prevention strategies for patients.

The team of Cédric Galera, researcher at the Bordeaux Population Health Center (Inserm/Université de Bordeaux) and child psychiatrist, working with UK, Swedish and Canadian teams, therefore decided to analyse the data of more than 2,000 children from the large-scale Quebec Longitudinal Study of Child Development cohort. The children were followed from 5 months to 17 years of age. They were seen multiple times in early childhood (5 months to 5 years of age), middle childhood (6 to 12 years of age) and in adolescence (13 to 17 years of age).

ADHD and other disorders

On these occasions, the children were evaluated on the severity of any ADHD symptoms they had as well as their physical condition (general health, any illnesses, etc.). These data were reported to the researchers by the person who knew the child best in early childhood, by teachers in middle childhood, and by the child itself in adolescence.

Based on these data and taking into account multiple confounding factors, the scientists carried out statistical analyses to measure the associations between presenting ADHD symptoms and developing certain subsequent physical disorders, and conversely, between presenting physical problems in childhood and then developing subsequent ADHD symptoms.

‘This is the most comprehensive analysis evaluating the temporal links between ADHD symptoms and a wide range of medical conditions, including skin problems, infections, injuries, sleep disorders and other chronic diseases. We sought to evaluate the possible longitudinal associations between ADHD symptoms and a wide range of physical conditions, taking into account several confounding factors,’ explains Galera, who is also the first author of the study.

The scientists showed that having ADHD symptoms in early childhood was associated with a high BMI in middle childhood and adolescence, as well as unintentional injuries in adolescence. Conversely, having presented with unintentional injuries in early childhood was associated with subsequent onset of ADHD symptoms in middle childhood and adolescence. Finally, restless legs syndrome in early childhood also increased the risk of ADHD in middle childhood.

‘By shedding light on the links between ADHD and various comorbidities, as well as the timescale at which they occur, our study reinforces the idea that physical and mental health problems are intertwined, and highlights the need for healthcare professionals of all disciplines to work together in a better way. For example, physicians should be able to refer patients to other disciplinary fields as needed. The earlier we intervene, the more we prevent the evolving risks associated with ADHD,’ emphasises Galera.

To go further, the team will continue to focus on these links by studying data collected on young adults between the ages of 20 and 25. In addition, the scientists would also like to carry out similar work using French data, based on the large cohorts set up in the country, such as the French Longitudinal Study of Children (Elfe).