Establishing a gluten threshold in celiac disease

Nutrition Research Newsletter, Feb, 2007

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten--the maj or protein fraction contained in the cereals wheat, rye, and barley--in genetically susceptible persons. The standard treatment of CD involves the consumption of a diet completely devoid of gluten proteins, a so-called gluten-free diet (GFD). However, it is almost impossible to maintain a diet with a zero gluten content because gluten contamination is very common in food. Even products specifically targeted to dietary treatment of CD may contain trace amounts of gluten protein, either because of the cross-contamination of originally gluten-free cereals during their milling, storage, and manipulation or because of the presence of wheat starch as a major ingredient.

The potential toxicity of trace amounts of gluten is still unclear. Establishing a safe threshold of gluten consumption for CD patients is a matter of major public health importance, particularly in light of the recent reports concerning the high prevalence of the disease worldwide.

A prospective, double-blind, placebo-controlled multicenter trial to investigate the toxicity of gluten traces in the celiac diet was performed. Subjects included adults with biopsy-proven CD who had consumed a GFD for e"2 years and who were in apparent good health.

The patients qualifying for the trial underwent a screening and a dietary interview (t--1). They were asked to maintain a strict GFD during the study period. After 1 month the subjects returned for a baseline evaluation (to) which involved 1) a clinical examination, 2) a dietary interview, 3) blood collection for serum anti-tTG antibody and anti-gliadin antibody (AGA) measurements, and 4) an endoscopy and small-intestinal biopsy. While still adhering to a strict GFD, the patients were randomly assigned to ingest daily and for 90 days a capsule containing either 10 mg purified gluten, 50 mg purified gluten, or 50 mg cornstarch as a placebo. After completing the 3-month challenge (t--1), the patients repeated the same clinical, serologic, and histologic tests as at (to).

At (to) the median villous height/crypt depth (Vh/Cd) in the small-intestinal mucosa was significantly lower and the intraepithelial lymphocyte (IEL) count (X 100 enterocytes) significantly higher in the CD patients (Vh/Cd: 2.20; 95% CI: 2.11,2.89; IEL: 27; 95% CI: 23, 24) than in 20 non-CD control subjects (Vh/Cd: 2.87; 95% CI: 25.0, 3.09; IEL: 22; 95% CI: 18, 24). One patient (challenged with 10 mg gluten) developed a clinical relapse. At (t-1), the percentage change in Vh/Cd was 9% (95% CI: 3%, 15%) in the placebo group(n=13),-1% (-18%, 68%) in the 10-mg group (n=13), and -20% (-22%,-13%) in the 50-mg group (n = 13). No significant differences in the IEL count were found between the three groups.

It is concluded that the ingestion of contaminating gluten should be kept lower than 50 mg/d in the treatment of CD. C. Catssi, E. Fabiani, G Iacono, et al. A Prospective, Double-Blind, Placebo-Controlled Trial to Establish a Safe Gluten Threshold for Patients with Celiac Disease. Am J Clin Nutr; 85:160-166 (January 2007). [Correspondence: A. Fasano, Mucosal Biology Research Center, University of Maryland School of Medicine, 20 Penn STree, Room 345, Baltimore, MD 21201. E-mail: afasano@mbrc.umaryland.edu.]