“Celiac disease (CD) patients adhering to a gluten-free diet (GFD) are exposed frequently to low levels of gluten that contribute to symptoms and persistent intestinal histologic damage.”
- excerpted from The American Journal of Clinical Nutrition, Volume 107, Issue 2, 1 February 2018 1
Celiac disease (CD) is the most common autoimmune gastrointestinal disease, affecting ∼1% of the world population . There are currently no US Food and Drug Administration (FDA)–approved treatments, other than a gluten-free diet (GFD), which is exceedingly difficult to maintain.
The average Western diet contains ∼5–15 g gluten/d . Gluten ingestion as low as 50 mg/d can be harmful to some celiac patients . The elimination of 99% of gluten from a diet may still be insufficient to avoid symptoms and histologic damage.
The FDA has established a guideline that foods labeled gluten free must contain <20 ppm gluten . However, there are difficulties with currently approved analytical methods for the detection and quantification of gluten in certain foods (e.g., fermented and hydrolyzed foods) .
There is an unmet need to protect against unintended gluten ingestion, particularly since persistent uncontrolled gluten exposure is known to lead to life-long health issues and co-morbidities such as anemia, malnutrition, and lymphoma. As such, investigational drugs in clinical development are generally intended to be used as an adjunct to a GFD.
Despite the obvious need to protect CD patients against exposure to gluten consumption, there is surprisingly very little known about the quantity of gluten that is accidently consumed episodically and continually for those on a GFD. Much has been written about GFDs and the complexities, difficulties, and challenges associated with maintaining strict adherence across social and demographic groups and behaviors . However, we are unaware of any studies that attempt to analytically determine the actual quantity of gluten that is consumed while on a GFD.
In this work, we performed a meta-analysis based on data from clinical studies that provided key information needed to determine the amount of gluten that CD patients consume while attempting to follow a GFD.
We analyzed prior clinical data to determine how much gluten is accidentally consumed while on a GFD. The aim was to understand the range of gluten consumption for a wide distribution of CD patients.
A meta-analysis was conducted on data from 2 different clinical programs:
1) measurements of gluten in stool and urine in CD and non-CD populations; and
2) analysis of data from trials for the investigational therapeutic latiglutenase.
The stool and urine studies included controlled gluten challenges. A calibration factor was applied that allowed normal ingestion of gluten to be computed from the urine and stool measurements. From the latiglutenase trial data, a determination of gluten consumption was made by estimating how much gluten was eliminated from patients’ diets due to a trial effect that led to improved histology even in the placebo group.
The average inadvertent exposure to gluten by CD individuals on a GFD was estimated to be ∼150–400 (mean) and ∼100–150 (median) mg/d using the stool test and ∼300–400 (mean) and ∼150 (median) mg/d using the urine test.
The analyses of the latiglutenase data for CD individuals with moderate to severe symptoms indicate that patients ingested significantly >200 mg/d of gluten.
These surrogate biomarkers of gluten ingestion indicate that many individuals following a GFD regularly consume sufficient gluten to trigger symptoms and perpetuate intestinal histologic damage.
Read the complete study here
- 1 The American Journal of Clinical Nutrition, Volume 107, Issue 2, 1 February 2018, Pages 201–207, https://doi.org/10.1093/ajcn/nqx049