Food additive emulsifiers and the risk of type 2 diabetes: analysis of data from the NutriNet-Santé prospective cohort study.

BACKGROUND: Experimental studies have suggested potential detrimental effects of emulsifiers on gut microbiota, inflammation, and metabolic perturbations. We aimed to investigate the associations between exposures to food additive emulsifiers and the risk of type 2 diabetes in a large prospective cohort of French adults. METHODS: We analysed data from 104 139 adults enrolled in the French NutriNet-Santé prospective cohort study from May 1, 2009, to April 26, 2023; 82 456 (79·2%) were female and the mean age was 42·7 years (SD 14·5). Dietary intakes were assessed with three 24 h dietary records collected over three non-consecutive days, every 6 months. Exposure to additive emulsifiers was evaluated through multiple food composition databases and ad-hoc laboratory assays. Associations between cumulative time-dependent exposures to food additive emulsifiers and the risk of type 2 diabetes were characterised with multivariable proportional hazards Cox models adjusted for known risk factors. The NutriNet-Santé study is registered at ClinicalTrials.gov (NCT03335644). FINDINGS: Of 104 139 participants, 1056 were diagnosed with type 2 diabetes during follow-up (mean follow-up duration 6·8 years [SD 3·7]). Intakes of the following emulsifiers were associated with an increased risk of type 2 diabetes: total carrageenans (hazard ratio [HR] 1·03 [95% CI 1·01-1·05] per increment of 100 mg per day, p<0·0001), carrageenans gum (E407; HR 1·03 [1·01-1·05] per increment of 100 mg per day, p<0·0001), tripotassium phosphate (E340; HR 1·15 [1·02-1·31] per increment of 500 mg per day, p=0·023), acetyl tartaric acid esters of monoglycerides and diglycerides of fatty acids (E472e; HR 1·04 [1·00-1·08] per increment of 100 mg per day, p=0·042), sodium citrate (E331; HR 1·04 [1·01-1·07] per increment of 500 mg per day, p=0·0080), guar gum (E412; HR 1·11 [1·06-1·17] per increment of 500 mg per day, p<0·0001), gum arabic (E414; HR 1·03 [1·01-1·05] per increment of 1000 mg per day, p=0·013), and xanthan gum (E415, HR 1·08 [1·02-1·14] per increment of 500 mg per day, p=0·013). INTERPRETATION: We found direct associations between the risk of type 2 diabetes and exposures to various food additive emulsifiers widely used in industrial foods, in a large prospective cohort of French adults. Further research is needed to prompt re-evaluation of regulations governing the use of additive emulsifiers in the food industry for better consumer protection. FUNDING: European Research Council, French National Cancer Institute, French Ministry of Health, IdEx Université de Paris, and Bettencourt-Schueller Foundation.

Food additives impair gut microbiota from healthy individuals and IBD patients in a colonic in vitro fermentation model.

Intestinal fibrosis is a long-term complication of inflammatory bowel diseases (IBD). Changes in microbial populations have been linked with the onset of fibrosis and some food additives are known to promote intestinal inflammation facilitating fibrosis induction. In this study, we investigated how polysorbate 80, sucralose, titanium dioxide, sodium nitrite and maltodextrin affect the gut microbiota and the metabolic activity in healthy and IBD donors (patients in remission and with a flare of IBD). The Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) with a static (batch) configuration was used to evaluate the effects of food additives on the human intestinal microbiota. Polysorbate 80 and sucralose decreased butyrate-producing bacteria such as Roseburia and Faecalibacterium prausnitzii. Both compounds, also increased bacterial species positively correlated with intestinal inflammation and fibrosis (i.e.: Enterococcus, Veillonella and Mucispirillum schaedleri), especially in donors in remission of IBD. Additionally, polysorbate 80 induced a lower activity of the aryl hydrocarbon receptor (AhR) in the three groups of donors, which can affect the intestinal homeostasis. Maltodextrin, despite increasing short-chain fatty acids production, promoted the growth of Ruminococcus genus, correlated with higher risk of fibrosis, and decreased Oscillospira which is negatively associated with fibrosis. Our findings unveil crucial insights into the potential deleterious effects of polysorbate 80, sucralose and maltodextrin on human gut microbiota in healthy and, to a greater extent, in IBD patients.

Food additive emulsifiers and cancer risk: Results from the French prospective NutriNet-Santé cohort.

BACKGROUND: Emulsifiers are widely used food additives in industrially processed foods to improve texture and enhance shelf-life. Experimental research suggests deleterious effects of emulsifiers on the intestinal microbiota and the metabolome, leading to chronic inflammation and increasing susceptibility to carcinogenesis. However, human epidemiological evidence investigating their association with cancer is nonexistent. This study aimed to assess associations between food additive emulsifiers and cancer risk in a large population-based prospective cohort. METHODS AND FINDINGS: This study included 92,000 adults of the French NutriNet-Santé cohort without prevalent cancer at enrolment (44.5 y [SD: 14.5], 78.8% female, 2009 to 2021). They were followed for an average of 6.7 years [SD: 2.2]. Food additive emulsifier intakes were estimated for participants who provided at least 3 repeated 24-h dietary records linked to comprehensive, brand-specific food composition databases on food additives. Multivariable Cox regressions were conducted to estimate associations between emulsifiers and cancer incidence. Overall, 2,604 incident cancer cases were diagnosed during follow-up (including 750 breast, 322 prostate, and 207 colorectal cancers). Higher intakes of mono- and diglycerides of fatty acids (FAs) (E471) were associated with higher risks of overall cancer (HR high vs. low category = 1.15; 95% CI [1.04, 1.27], p-trend = 0.01), breast cancer (HR = 1.24; 95% CI [1.03, 1.51], p-trend = 0.04), and prostate cancer (HR = 1.46; 95% CI [1.09, 1.97], p-trend = 0.02). In addition, associations with breast cancer risk were observed for higher intakes of total carrageenans (E407 and E407a) (HR = 1.32; 95% CI [1.09, 1.60], p-trend = 0.009) and carrageenan (E407) (HR = 1.28; 95% CI [1.06, 1.56], p-trend = 0.01). No association was detected between any of the emulsifiers and colorectal cancer risk. Several associations with other emulsifiers were observed but were not robust throughout sensitivity analyses. Main limitations include possible exposure measurement errors in emulsifiers intake and potential residual confounding linked to the observational design. CONCLUSIONS: In this large prospective cohort, we observed associations between higher intakes of carrageenans and mono- and diglycerides of fatty acids with overall, breast and prostate cancer risk. These results need replication in other populations. They provide new epidemiological evidence on the role of emulsifiers in cancer risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT03335644.

Carrageenan impact on digestive proteolysis of meat proteins in meatballs or soluble hydrolyzed collagen.

In a health-conscious age, vivid discussion has been made on the healthfulness of processed foods and food additives. This study focuses on carrageenan (CGN), an approved but debated family of sulphated galactans from algae used as gelling, thickening and stabilizing agents but with indications of possible adverse effects, including as an inhibitor of digestive proteolysis. To challenge this inhibitory hypothesis, food-grade kappa-, iota and lambda-CGN preparations were used to produce beef meatballs whose proteolysis was studied using an in vitro digestion model coupled to various proteomic analyses. Results show that CGN anti-nutritional effects are abolished in beef meatballs. Specifically, proteomic analysis of gastric digesta of myosin light chain 1 (MYL1), alpha skeletal muscle (ACTA1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and fructose-bisphosphate aldolase (ALDOA) reveal no appreciable differences in the profiles of bioaccessible peptides. Separate digestions of a soluble collagen hydrolysate show CGN does inhibit proteolysis of soluble collagen, therefore supporting the notion that the meat matrix confers a shielding effect that eliminates CGN ability to interfere with digestive proteolysis. Thus, this work shows that CGN ability to hinder digestive proteolysis may not apply to all foods and contributes evidence important to the discussions on CGN uses, indications and regulatory status.

Industrial Use of Phosphate Food Additives: A Mechanism Linking Ultra-Processed Food Intake to Cardiorenal Disease Risk?

The consumption of ultra-processed food (UPF) keeps rising, and at the same time, an increasing number of epidemiological studies are linking high rates of consumption of UPF with serious health outcomes, such as cardiovascular disease, in the general population. Many potential mechanisms, either in isolation or in combination, can explain the negative effects of UPF. In this review, we have addressed the potential role of inorganic phosphate additives, commonly added to a wide variety of foods, as factors contributing to the negative effects of UPF on cardiorenal disease. Inorganic phosphates are rapidly and efficiently absorbed, and elevated serum phosphate can lead to negative cardiorenal effects, either directly through tissue/vessel calcification or indirectly through the release of mineral-regulating hormones, parathyroid hormone, and fibroblast growth factor-23. An association between serum phosphate and cardiovascular and bone disease among patients with chronic kidney disease is well-accepted by nephrologists. Epidemiological studies have demonstrated an association between serum phosphate and dietary phosphate intake and mortality, even in the general American population. The magnitude of the role of inorganic phosphate additives in these associations remains to be determined, and the initial step should be to determine precise estimates of population exposure to inorganic phosphate additives in the food supply.

Aspartame Safety as a Food Sweetener and Related Health Hazards.

Aspartame is the methyl-ester of the aspartate-phenylalanine dipeptide. Over time, it has become a very popular artificial sweetener. However, since its approval by the main food safety agencies, several concerns have been raised related to neuropsychiatric effects and neurotoxicity due to its ability to activate glutamate receptors, as well as carcinogenic risks due to the increased production of reactive oxygen species. Within this review, we critically evaluate reports concerning the safety of aspartame. Some studies evidenced subtle mood and behavioral changes upon daily high-dose intake below the admitted limit. Epidemiology studies also evidenced associations between daily aspartame intake and a higher predisposition for malignant diseases, like non-Hodgkin lymphomas and multiple myelomas, particularly in males, but an association by chance still could not be excluded. While the debate over the carcinogenic risk of aspartame is ongoing, it is clear that its use may pose some dangers in peculiar cases, such as patients with seizures or other neurological diseases; it should be totally forbidden for patients with phenylketonuria, and reduced doses or complete avoidance are advisable during pregnancy. It would be also highly desirable for every product containing aspartame to clearly indicate on the label the exact amount of the substance and some risk warnings.

Possible Signaling Pathways in the Gut Microbiota-Brain Axis for the Development of Parkinson's Disease Caused by Chronic Consumption of Food Additives.

It is well-known that consumption of synthetic and natural food additives has both positive and negative effects in the human body. However, it is not clear yet how food additives are related to the development of Parkinson's disease. Therefore, in this review work, the food additive effects related to the gut microbiota-brain axis and the processes that are carried out to develop Parkinson's disease are studied. To this end, a systematic literature analysis is performed with the selected keywords and the food additive effects are studied to draw possible routes of action. This analysis leads to the proposition of a model that explains the pathways that relate the ingestion of food additives to the development of Parkinson's disease. This work motivates further research that ponders the safety of food additives by measuring their impacts over the gut microbiota-brain axis.

Consumers' knowledge and attitudes about food additives in the UAE.

The use of food additives (FAs) in food manufacturing is a well-accepted practice worldwide. Inadequate knowledge concerning their safety may cause negative attitude surrounding their use. This would potentially impact the purchase of foods that the consumer perceives as containing FAs. This study aimed to assess knowledge and attitudes of consumers towards the use and safety of FAs in the UAE. A cross-sectional study was conducted using an online survey distributed via social media platforms (n = 1037). Less than one-third of the participants (26.7%) in this study stated that they knew what FAs are. About half the respondents believed that organic products did not contain FAs. The proportion of respondents who reported that the purpose of adding FAs is to extend shelf life, better the taste and aroma of food, enhance nutritional value, improve consistency and texture, and boost appearance and color was 92.1%, 75.0%, 23.5%, 56.6%, and 69.4%, respectively. Around 61% believed that all FAs were harmful to human health. The level of FA knowledge increased with age and education level. About 60% of the respondents reported that food labels did not provide sufficient information about FAs. The most preferred platforms for consumers to receive information about FAs were social media (41.1%), followed by brochures (24.6%). Overall, the UAE population had inadequate knowledge and a hesitant attitude concerning FAs. The municipalities and food industry should play an active role in educating the public to prevent and reduce any possible adverse attitudes towards processed food products.

Information on food additives on food labels in Brazil: a critical analysis.

Questions about the safety of food additives and their consumption have been raised in recent years. The increased exposure to these substances, either by intake of ultra-processed foods or by the broad use and combination of various categories of additives, may be related to higher risks to consumer health. This article comments on the results of a study that quantified and characterized food additives found on the labels of 9,856 packaged foods and beverages available in Brazilian supermarkets. The study adopted a field diary method to record and analyze nonconformities in the lists of ingredients. The objective of this article is to discuss the use of additives identified on the labels and the limitations of Brazilian legislation, which should guarantee the right to information and health.

Food Color Additives in Hazardous Consequences of Human Health: An Overview.

Food color additives are used to make food more appetizing. The United States Food and Drug Administration (FDA) permitted nine artificial colorings in foods, drugs, and cosmetics, whereas the European Union (EU) approved five artificial colors (E-104, 122, 124, 131, and 142) for food. However, these synthetic coloring materials raise various health hazards. The present review aimed to summarize the toxic effects of these coloring food additives on the brain, liver, kidney, lungs, urinary bladder, and thyroid gland. In this respect, we aimed to highlight the scientific evidence and the crucial need to assess potential health hazards of all colors used in food on human and nonhuman biota for better scrutiny. Blue 1 causes kidney tumor in mice, and there is evidence of death due to ingestion through a feeding tube. Blue 2 and Citrus Red 2 cause brain and urinary bladder tumors, respectively, whereas other coloring additives may cause different types of cancers and numerous adverse health effects. In light of this, this review focuses on the different possible adverse health effects caused by these food coloring additives, and possible ways to mitigate or avoid the damage they may cause. We hope that the data collected from in vitro or in vivo studies and from clinical investigations related to the possible health hazards of food color additives will be helpful to both researchers and the food industry in the future.

Children With Celiac Disease Consume Specific Food Additives More Frequently Compared to Children Without Celiac Disease.

BACKGROUND: Gluten-free foods often contain food additives to improve palatability, but the long-term effects on the human gastrointestinal tract are not well known. AIMS: This study aimed to quantify frequency of food additive exposure in children with and without celiac disease (CD). METHODS: Children with and without CD were enrolled and demographic data and three-day diet records were obtained. Foods were classified as gluten-free products (GFP) and "processed food", and were evaluated for presence of select food additives: polysorbate 80, carboxymethylcellulose, xanthan gum, guar gum, soy lecithin, titanium dioxide, carrageenan, maltodextrin, and aluminosilicates. The frequency of exposure was described. RESULTS: Twenty-eight participants were included in final analysis. Children with CD had a higher number of daily exposures to xanthan gum (5.3 ± 3.1 vs 2.3 ± 2.4; p = 0.009), but similar exposures to the other additives. GFP contributed 29% of total calories in the GF diet. Both groups had similar intake of processed foods. Comparing GFP and gluten-containing processed foods, 68% vs. 25% contained at least one food additive of interest (p < 0.0001); in the celiac group, those with higher consumption of GFP tended to have a higher frequency of exposure to food additives (p = 0.09). CONCLUSION: A gluten-free diet and consumption of GFP may contribute to differences in food additive intake; quantifying food additive exposures and their effect on humans requires further study.

Risk assessment of azo dyes as food additives: Revision and discussion of data gaps toward their improvement.

The food industry uses dyes mainly to overcome color loss during the processing and storage of products, with the azo dyes currently being the most employed. Studies on the safety of using these dyes in foods started in the 1950s and have indicated the potential for concern. This review discusses the risk assessment of food intake containing artificial azo dyes. There are case reports and, subsequently, double-blind placebo-controlled trials in some individuals who may experience adverse effects from the intake of azo dyes, but it is unclear whether these adverse effects are restricted to specific populations or more generalized. In view of this, different toxicological endpoints are evaluated to verify toxic effects in in vitro and in vivo models and to establish the no observed adverse effect level. Exposure estimation studies have shown that human exposure to azo dyes via oral intake is mainly below the acceptable daily intake established by advisory bodies. However, most countries do not have studies that estimate the oral intake of azo dyes. In this case, local food diversity and racial-ethnic specificities are not considered when stating the exposure estimate is below the acceptable daily intake for the human population and thus may not represent actual intake. Concerning the scenario established above, this review discusses the most critical gaps to be overcome to contribute to the direction of future studies and the development of more effective public policies concerning the safety of the intake of artificial azo dyes.

Information on food additives on food labels in Brazil: a critical analysis / Informação sobre aditivos alimentares nos rótulos de alimentos no Brasil: análise crítica

ABSTRACT Questions about the safety of food additives and their consumption have been raised in recent years. The increased exposure to these substances, either by intake of ultra-processed foods or by the broad use and combination of various categories of additives, may be related to higher risks to consumer health. This article comments on the results of a study that quantified and characterized food additives found on the labels of 9,856 packaged foods and beverages available in Brazilian supermarkets. The study adopted a field diary method to record and analyze nonconformities in the lists of ingredients. The objective of this article is to discuss the use of additives identified on the labels and the limitations of Brazilian legislation, which should guarantee the right to information and health.

RESUMO Nos últimos tempos, questões vêm sendo levantadas sobre a segurança no uso de aditivos alimentares e em seu consumo. verificou-se que o aumento da exposição a essas substâncias, seja pela ingestão mais frequente de alimentos ultraprocessados ou pela ampla utilização e combinação de várias categorias de aditivos pela indústria, pode estar relacionado ao maior risco à saúde do consumidor. Um estudo quantificou e caracterizou aditivos alimentares encontrados nos rótulos de 9.856 alimentos e bebidas embalados disponíveis nos supermercados brasileiros. nele, foi adotado um diário de campo para registro de falhas e inconformidades nas informações presentes nas listas de ingredientes, sendo, por fim, analisadas qualitativamente e descritas de forma narrativa. Com base nisso, o objetivo deste comentário é apresentar e discutir o uso desses aditivos identificados nos rótulos e as limitações da legislação brasileira, que deveria garantir o direito à informação e a saúde da população.

Processed Food as a Risk Factor for the Development and Perpetuation of Crohn's Disease-The ENIGMA Study.

(1) Background: Developing countries have experienced a rapid recent rise in Inflammatory Bowel Disease (IBD) incidence and emerging evidence suggests processed foods and food additives may predispose one to the development and perpetuation of Crohn's disease (CD). The aim of this study was to evaluate processed food and food additive intake in CD patients and controls, in Australia (high CD incidence), Hong Kong (intermediate incidence) and mainland China (emerging incidence). (2) Methods: In 274 CD patients (CD), 82 first-degree relatives (FDR), 83 household members (HM) and 92 healthy unrelated controls (HC) from Australia (n = 180), Hong Kong (HK) (n = 160) and mainland China (n = 191) we estimated early life (0-18 years), recent (12 months), and current processed and food additive intake, using validated questionnaires and a 3-day-food diary. (3) Results: Early life processed food intake: Combining all regions, CD were more likely to have consumed soft drinks and fast foods than HM, more likely to have consumed processed fruit and snacks than their FDR, and more likely to have consumed a range of processed foods than HC. HK and China CD patients were more likely to have consumed a range of processed foods than HC. Recent food-additive intake (12-months): Combining all regions, CD patients had significantly higher intakes of aspartame and sucralose, and polysorbate-80, than HC, and more total emulsifiers, artificial sweeteners, and titanium dioxide than FDR and HC. HK and China CD patients had a higher intake of almost all food additives than all controls. Current additive intake (3-days): Australian and HK CD patients had higher total food-additive intake than FDR, and HK CD patients had a higher intake of total food-additives and emulsifiers than HM. (4) Conclusions: CD patients have been exposed to more processed food and food additives than control groups, which may predispose them to CD development and ongoing inflammation.

Hypersensitivity Reactions to Food Additives-Preservatives, Antioxidants, Flavor Enhancers.

There have been reports of food hypersensitivity reactions to food additives (HFA) for many years. The mechanisms of HFA and their frequency are difficult to precisely define, as most of the data come from outdated studies with poor methodology. In 2020, the European Food Safety Authority completed a review of additives, examining their influence on the occurrence of HFA, but did not include all of them. The aim of this review is to systematise knowledge about selected groups of food additives (FAs) and the HFA induced by them. We also briefly discuss the issues of diagnosis and therapy in this disease. FAs are commonly used in prosscessed foods, but HFA appears to be a rare phenomenon. Identification of the FA responsible for hypersensitivity and its treatment is difficult. Diagnosis is a challenge for the clinician and for the patient. A food diary is a helpful diagnostic tool. It allows diet therapy to be monitored based on the partial or complete elimination of products containing a harmful additive. An elimination diet must not be deficient, and symptomatic pharmacotherapy may be necessary if its application is ineffective. Taking all this into account, we conclude that it is necessary to conduct randomised multicentre studies based on the double-blind placebo control protocol in this field.

Food Additives Associated with Gut Microbiota Alterations in Inflammatory Bowel Disease: Friends or Enemies?

During the 21st century, the incidence and prevalence of inflammatory bowel disease (IBD) is rising globally. Despite the pathogenesis of IBD remaining largely unclear, the interactions between environmental exposure, host genetics and immune response contribute to the occurrence and development of this disease. Growing evidence implicates that food additives might be closely related to IBD, but the involved molecular mechanisms are still poorly understood. Food additives may be categorized as distinct types in accordance with their function and property, including artificial sweeteners, preservatives, food colorant, emulsifiers, stabilizers, thickeners and so on. Various kinds of food additives play a role in modifying the interaction between gut microbiota and intestinal inflammation. Therefore, this review comprehensively synthesizes the current evidence on the interplay between different food additives and gut microbiome alterations, and further elucidates the potential mechanisms of food additives-associated microbiota changes involved in IBD.

Toxicological and Teratogenic Effect of Various Food Additives: An Updated Review.

Scientific evidence is mounting that synthetic chemicals used as food additives may have harmful impacts on health. Food additives are chemicals that are added to food to keep it from spoiling, as well as to improve its colour and taste. Some are linked to negative health impacts, while others are healthy and can be ingested with little danger. According to several studies, health issues such as asthma, attention deficit hyperactivity disorder (ADHD), heart difficulties, cancer, obesity, and others are caused by harmful additives and preservatives. Some food additives may interfere with hormones and influences growth and development. It is one of the reasons why so many children are overweight. Children are more likely than adults to be exposed to these types of dietary intakes. Several food additives are used by women during pregnancy and breast feeding that are not fully safe. We must take specific precaution to avoid consuming dangerous compounds before they begin to wreak havoc on our health. This study is intended to understand how the preservatives induce different health problem in the body once it is consumed. This review focuses on some specific food additives such as sodium benzoate, aspartame, tartrazine, carrageenan, and potassium benzoate, as well as vitamin A. Long-term use of food treated with the above-mentioned food preservatives resulted in teratogenicity and other allergens, according to the study. Other health issues can be avoided in the future by using natural food additives derived from plants and other natural sources.