U.S. Allows A Food Additive That Is Banned In The EU

Written by Mikaela Conley on January 14, 2025. Posted in Current News

Titanium dioxide, the most widely used whitening pigment in the world, has been linked to adverse health effects, particularly genotoxicity and intestinal inflammation

It is applied as a food coloring and a whitening agent to chewing gum, cakes, candies, breads and ice cream.

Because of health risks, France banned titanium dioxide, or TiO2, as a food additive in 2020.

Two years later the European Union (EU) also banned titanium dioxide as a food additive. But in the U.S., titanium dioxide is found all over the grocery shelves.

Candy like Skittles, Starbursts and Jell-O, gum like Trident White peppermint gum and Mentos Freshmint Gum, cake products like Duncan Hines Creamy Vanilla Frosting and Nabisco Chips Ahoy! cookies are just a few of the myriad food items that contain the additive.

A significant body of research, mostly from rodent models and in vitro studies, has linked titanium dioxide with health risks related to the gut, including intestinal inflammation, alterations to the gut microbiota and more.

It is classified by the International Agency for Research on Cancer in Group 2B, as possibly carcinogenic to humans.

As a food additive, titanium dioxide and its nanoparticles in particular have been associated with DNA damage and cell mutations, which in turn, have the potential to cause cancer. When used as a food coloring, it is known as E171.

With the rise of nanotechnology, research in recent years has also shown the dangers of titanium dioxide or TiO2 nanoparticles, and their genotoxicity, which refers to a chemical agent’s ability to harm or damage DNA in cells, thus potentially causing cancer.

Over the last several years, nanoparticles have come under scrutiny for adverse health effects. Nanoparticles are ultrafine particles between 1 to 100 nanometers in diameter. (To put this in perspective, the average human hair is around 80,000 nanometers thick.)

Because of their size, which can be engineered and manipulated at the atomic or molecular level, nanoparticles exhibit unique physical, chemical and biological properties. Titanium dioxide is one of the most commonly produced nanoparticles in the world.

Studies of titanium dioxide as a food additive suggest health dangers

Numerous studies have linked titanium dioxide to genotoxicity and cytotoxicity. Genotoxicity refers to a chemical’s potential to cause DNA damage, which can, in turn, lead to cancer. Cytotoxicity is a general term that refers to a characteristic of being harmful to cells.

French researchers studied how and where E171 nanoparticles enter the bloodstream, first studying the route through pigs and then in vitro with human buccal cells, for a 2023 study published in the journal Nanotoxicology.

The research showed that the nanoparticles absorbed quickly through the mouth and then into the bloodstream, before damaging DNA and hindering cell regeneration.

In a 2016 study published in Scientifica (Cairo), Egyptian researchers examined the effects of titanium dioxide nanoparticles on the organs of mice by orally administering the food additive daily, for five days.

The results showed that the exposure produced “mild to moderate changes in the cytoarchitecture of brain tissue in a time-dependent manner.”

Furthermore, “Comet assay revealed the apoptotic DNA fragmentation, while PCR-SSCP pattern and direct sequencing showed point mutation of Presenilin 1 gene at exon 5, a gene linked to inherited forms of Alzheimer’s disease.”

The researchers wrote:

“From these findings, the present study concluded that TiO2NPs [titanium dioxide nanoparticles] is genotoxic and mutagenic to brain tissue which in turn might lead to Alzheimer’s disease incidence.”

For research published in 2022 study in the journal Food and Chemical Toxicology, scientists examined “the genotoxicity and the intracellular reactive oxygen species induction by physiologically relevant concentrations of three different TiO2 nanomaterials in Caco-2 and HT29-MTX-E12 intestinal cells, while considering the potential influence of the digestion process in the NMs’ physiochemical characteristics.”

They found a “DNA-damaging effect dependent on the nanomaterial,” along with the micronucleus assay suggesting “effects on chromosomal integrity, an indicator of cancer risk, in the HT29-MTX-E12 cells, for all the tested TiO2 nanomaterials.”

Researchers concluded that the results showcase “evidence of concern” regarding titanium dioxide used as a food additive.

In a study published in the journal Toxicology, researchers examined the effects of exposing the human colon cancer cell line (HTC116) to titanium dioxide food additives in vitro.

“In the absence of cytotoxicity, E171 was accumulated in the cells after 24 hours of exposure, increasing granularity and reactive oxygen species, inducing alterations in the molecular pattern of nucleic acids and lipids, and causing nuclei enlargement, DNA damage and tubulin depolymerization,” the scientists wrote.

Researchers removed the additive from the culture and then examined the results 48 hours later.

They found that “The removal of E171 was unable to reverse the alterations found after 24 h of exposure in colon cells. In conclusion, exposure to E171 causes alterations that cannot be reverted after 48 h if E171 is removed from colon cells.”

A review published in 2022 in the journal NanoImpact evaluated the latest research related to the genotoxic effects of titanium dioxide through in vivo studies and in vitro cell tests.

Researchers summarized the results by stating that TiO2 nanoparticles “could induce genotoxicity prior to cytotoxicity,” and “are likely to be genotoxic to humans.”

Inflammation of the intestines

Animal studies have shown that, when consumed as a food additive, titanium dioxide can induce intestinal inflammation.

In a 2019 study published in the journal Nanotoxicology, researchers recreated the first phase of digestion in mice and fed them titanium dioxide, then examined whether accumulation occurred in the organs.

Researchers wrote:

“Significant accumulation of titanium was observed in the liver and intestine of E171-fed mice; in the latter a threefold increase in the number of TiO2 particles was also measured.

Titanium accumulation in the liver was associated with necroinflammatory foci containing tissue monocytes/macrophages. Three days after the last dose, increased superoxide production and inflammation were observed in the stomach and intestine.

Overall, [this] indicates that the risk for human health associated with dietary exposure to E171 needs to be carefully considered.”

A study published in the Journal of Agricultural and Food Chemistry in 2019 sought to examine the effects of titanium dioxide on intestinal inflammation.

Researchers did this by feeding rats titanium dioxide nanoparticles and found that, after the course of two to three months, the animals had lower body weights and induced intestinal inflammation.

The researchers also found the nanoparticles altered gut microbiota composition and aggravated chronic colitis.

The rats also experienced reduced populations of CD4+T cells (which are cells that help organize immune responses by prompting other immune cells to fight infection), regulatory T cells and white blood cells in mesenteric lymph nodes.

The researchers wrote:

“Dietary TiO2 nanoparticles could interfere with the balance of the immune system and dynamic of gut microbiome, which may result in low-grade intestinal inflammation and aggravated immunological response to external stimulus, thus introducing potential health risk.”

For a mini-review published in the journal Particle and Fibre Technology in 2021, scientists wanted to evaluate whether TiO2 particles contributed to the development and/or exacerbation of irritable bowel disease and whether they altered the four elements of intestinal barrier function: the intestinal microbiota, the immune system, the mucus layer and the epithelium.

The breakdown of these four elements can contribute to autoimmune, neurological, inflammatory, infectious and metabolic diseases.

Following their review, the researchers concluded:

“Data indicate that TiO2 is able to alter the four compartments of IBF and to induce a low-grade intestinal inflammation associated or not with pre-neoplastic lesions.”

Neurotoxicity

A 2025 paper published in Alzheimer’s and Dementia provides prime evidence that provides prime evidence that nanoparticles of TiO2 (used in food and cosmetics) and Carbon Black (found in rubber and pigments) bind to a specific receptor in neurons, corrupting its signaling and causing oxidative stress, inflammation and overproduction of toxic amyloid-beta peptides, which are key markers of Alzheimer’s disease.

This study sheds light on how exposure to these particles might increase the risk of neurodegenerative diseases and highlights the need for strategies to mitigate their impact on brain health.

Scientists analyzed research that examined how titanium dioxide nanoparticles interact with the brain for a 2015 review published in Nanoscale Research Letters.

The researchers wrote:

“Once the TiO2 NPs are translocated into the central nervous system through [certain] pathways, they may accumulate in the brain regions. For their slow elimination rates, those NPs could remain in the brain zones for a long period, and the Ti contents would gradually increase with repeated exposure.”

After reviewing dozens of studies, the scientists concluded:

“Long-term or chronic exposure to TiO2 nanoparticles could potentially lead to the gradually increased Ti contents in the brain, which may eventually induce impairments on the neurons and glial cells and lead to CNS dysfunction as a consequence.”

For research published in the Archives of Toxicology in 2020, scientists fed one group of mice a solution containing titanium dioxide for one month and compared it to those that did not receive the additive.

They found “the richness and evenness of gut microbiota were remarkably decreased and the gut microbial community compositions were significantly changed” in the titanium dioxide group when compared with the control group.

The tests also revealed that titanium dioxide exposure could cause locomotor dysfunction, or mobility issues “by elevating the excitement of enteric neurons, which might spread to the brain via gut-brain communication by vagal pathway.”

The researchers concluded:

“These findings provide valuable insights into the novel mechanism of TiO2NP-induced neurotoxicity. Understanding the microbiota-gut-brain axis will provide the foundation for potential therapeutic or prevention approaches against TiO2NP-induced gut and brain-related disorders.”

In a 2020 study published in the Journal of Trace Elements in Medicine and Biology, researchers conducted an in vitro experiment to analyze the effects of TiO2 nanoparticles on a human neuroblastoma (SH-SY5Y) cell line.

The scientists evaluated “reactive oxygen species (ROS) generation, apoptosis, cellular antioxidant response, endoplasmic reticulum stress and autophagy.”

The results showed that exposure to the nanoparticles “induced ROS generation in a dose-dependent manner, with values reaching up to 10-fold those of controls. Nrf2 nuclear localization and autophagy also increased in a dose-dependent manner. Apoptosis increased by 4- to 10-fold compared to the control group, depending on the dose employed.”

Promotion of obesity-related metabolic disorders

For a review published in 2023 in the journal Environmental Pollution, researchers examined E171 as a possible factor promoting obesity-related metabolic disorders.

Because gut microbiota plays an important role in immune function maintenance and development, and because titanium dioxide as a food additive has been shown to alter gut microbiota, researchers wanted to review:

“The dysregulations along the gut microbiota-immune system axis after oral TiO2 exposure compared to those reported in obese or diabetic patients, and to highlight potential mechanisms by which foodborne TiO2 nanoparticles may increase the susceptibility to develop obesity-related metabolic disorders.”

The study authors discovered recurrent changes in the gut microbiota composition when exposed to titanium dioxide nanoparticles, with an imbalance of intestinal symbiotic microbiota.

These changes and imbalances were also reported and played a role in the development of obesity, the authors wrote.

This highlights “foodborne TiO2 nanoparticles as an endocrine disruptor-like chemical promoting obesity-related disorders,” the authors concluded.

Colorectal tumors and preneoplastic lesions

In a study published in the journal Food and Chemical Toxicology in 2016, researchers investigated whether titanium dioxide exposure led to an increase in colorectal tumor creation in mice by using a colitis-associated cancer model.

By measuring tumor progression markers, the researchers found that mice given titanium dioxide experienced enhanced tumor formation in the distal colon.

There was also a decrease in cells that act as a protective barrier in the colon. The researchers wrote:

“These results suggest that E171 could worsen pre-existent intestinal diseases.”

In a 2017 study published in Scientific Reports, researchers exposed rats to human-relevant levels of E171 to examine the effects of intestinal inflammation and carcinogenesis.

They saw that “a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model.”

“Stimulation of immune cells isolated from Peyer’s Patches [which are clusters of lymphoid follicles found in the intestine] showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased,” the researchers wrote. “A 100-day titanium dioxide treatment promoted colon microinflammation and initiated preneoplastic lesions.”

The scientists concluded:

“These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO2 from dietary sources.”

Alterations in gut microbiota

Research has shown that, when ingested as a food additive, titanium dioxide and its nanoparticles can impact, alter and/or damage important protective bacteria in the gut, along with the metabolic pathways of gut bacteria.

In a 2023 study published in the journal Environmental Research, scientists examined the effect of titanium dioxide nanoparticles on important gut bacteria in mice.

Their results showed that:

“The growth inhibitory effects could be associated with cell membrane damage caused by titanium dioxide nanoparticles to the bacterial strains.

Metabolomics analysis showed that TiO2 NPs caused alterations in multiple metabolic pathways of gut bacteria, such as tryptophan and arginine metabolism, which were demonstrated to play crucial roles in regulating gut and host health.”

The researchers also found that four different neuroprotective metabolites “were significantly reduced” in urine and in vitro bacteria and vivo urine samples.

The researchers concluded:

“Increasing evidence implies that the gut microbiome plays a profound role in regulating host metabolism. Our results illustrated that TiO2 NPs hindered the growth of four beneficial gut bacterial strains.”

Australian researchers examined how titanium dioxide as a food additive affected gut microbiota in mice by orally administering it in drinking water.

The study, published in the journal Frontiers in Nutrition in 2019, found the treatment could:

“Alter the release of bacterial metabolites in vivo and affect the spatial distribution of commensal bacteria in vitro by promoting biofilm formation.

We also found reduced expression of the colonic mucin 2 gene, a key component of the intestinal mucus layer, and increased expression of the beta-defensin gene, indicating that titanium dioxide significantly impacts gut homeostasis.”

The changes were then linked to colonic inflammation, along with a higher expression of inflammatory cytokines, which are signal proteins that help with regulation.

The researchers concluded that titanium dioxide “impairs gut homeostasis which may in turn prime the host for disease development.”

This is taken from a long document. Read the rest here childrenshealthdefense.org

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