Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05864352 |
| Other study ID # |
21-122-MAN-XPD |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 22, 2021 |
| Est. completion date |
November 28, 2022 |
Study information
| Verified date |
May 2024 |
| Source |
University of Massachusetts, Lowell |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This proposal will quantify dietary exposure of a nano- food additive in the U.S. food
supply, and determine its impact on the human gut microbiome, gut inflammation, permeability
and oxidative stress. Titanium dioxide (TiO2, or E171 food grade additive) is used in
processed foods, with thousands of tons produced annually and an expected increase >8.9% from
2016 to 2025. Preclinical models demonstrate >99% of consumed TiO2 is retained within the
intestinal lumen and excreted in the feces. In animal models, dietary TiO2 causes shifts in
the gut microbiome, decreases acetate production, increases biofilm formation, and causes
profound disruption of gut homeostasis and intestinal tight junctions, due to the production
of reactive oxygen species and increased inflammation. However, the relation between chronic
TiO2 intake and human gut homeostasis has yet to be elucidated. France issued an executive
order to ban food grade TiO2 use after January 1st 2020, over serious safety concerns. Since
then, multiple European civil societies have jointly called for an executive order to ban
TiO2 across the EU. Typical TiO2 intake among U.S. adults remains to be documented, and there
are no known studies that estimate dietary exposure of TiO2 using a whole foods approach.
Therefore, the overarching goals of this project are to: 1) measure dietary TiO2 exposure in
a sample of U.S. adults, using dietary recalls and fecal TiO2 content; 2) determine how fecal
TiO2 content is related to gut dysbiosis, metatranscriptomics, intestinal inflammation,
permeability and oxidative stress.
Description:
The U.S. food supply contains large amounts of the food additive titanium dioxide (TiO2), but
its impact on human health is unknown. The widespread use of food-grade TiO2 (E171) includes
commonly consumed products, such as sweets, gums, white salad dressings, dairy creamers,
pharmaceutical fillers, and toothpaste. Production of TiO2 in the U.S. is expected to
increase more than 8.9% from 2016 to 2025. There are major limitations with current
estimations of dietary TiO2 intake in humans. Such limitations include assessing TiO2 content
solely from white-colored foods and including only foods with TiO¬2 labeled as such on its
packaging. Natural food products, however, may also contribute a substantial amount of TiO¬2
to the diet. There is also a large variation in the estimated ingestion of TiO2 between
studies which is likely due to differences in populations and varying food supplies,
variability in analytical method used for measuring TiO2, and absence of validated dietary
estimation tools to measure oral TiO2 exposure. Therefore, estimation of TiO¬2 dietary intake
and gut exposure is needed among a free-living U.S. population of adults with a wide
variation of intakes.
Pre-clinical models show that greater TiO2 oral exposure may lead to impaired gut health
through changes in gut bacterial content and function. TiO2 has been shown to damage
intestinal cells where small doses of TiO2 caused changes in normal activity, but not damage
to the cell's genetics. After very small particles of TiO2 are taken up by these intestinal
cells, it causes mild toxicity and disruption of the cell's function. In addition, very small
particles of TiO2 accumulate in intestinal cells and remodel the cell's community in the
small intestine, suggesting these particles may get absorbed into the body's blood and
general circulation. These results demonstrate that very small particles of TiO2 causes
harmful changes to the intestinal cells, is absorbed by the intestinal cells, and once
inside, can cause harmfulness and promote abnormal cellular function. There is an urgent need
for studies in humans to determine whether high versus low level exposure to TiO¬2 is related
to gut inflammation and disruption in gut function.
The current study will fill these research gaps by testing the hypothesis that long term
dietary exposure of TiO2 is related to gut inflammation and disturbs gut bacteria in humans.
This hypothesis will be tested for the first time via these specific aims: 1) to quantify
dietary TiO2 exposure by estimating dietary intake and measuring the fecal output of TiO2 in
80 adults; 2) to establish the relationship of dietary TiO2 with gut bacteria and their
activity; and 3) to determine whether dietary TiO2 exposure is related to gut inflammation
and associated inflammatory pathways.
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