A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease

Carlo Catassi, Elisabetta Fabiani, Giuseppe Iacono, Cinzia D'Agate, Ruggiero Francavilla, Federico Biagi, Umberto Volta, Salvatore Accomando, Antonio Picarelli, Italo De Vitis, Giovanna Pianelli, Rosaria Gesuita, Flavia Carle, Alessandra Mandolesi, Italo Bearzi, Alessio Fasano

Research output: Contribution to journalArticlepeer-review


Background: Treatment of celiac disease (CD) is based on the avoidance of gluten-containing food. However, it is not known whether trace amounts of gluten are harmful to treated patients. Objective: The objective was to establish the safety threshold of prolonged exposure to trace amounts of gluten (ie, contaminating gluten). Design: This was a multicenter, double-blind, placebo-controlled, randomized trial in 49 adults with biopsy-proven CD who were being treated with a gluten-free diet (GFD) for ≥2 y. The background daily gluten intake was maintained at 0), patients were assigned to ingest daily for 90 d a capsule containing 0, 10, or 50 mg gluten. Clinical, serologic, and histologic evaluations of the small intestine were performed at t0 and after the gluten microchallenge (t1). Results: At t0, 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, 34) than in 20 non-CD control subjects (Vh/Cd: 2.87; 95% CI: 2.50, 3.09; IEL: 22; 95% CI: 18, 24). One patient (challenged with 10 mg gluten) developed a clinical relapse. At t1, 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 3 groups. Conclusions: The ingestion of contaminating gluten should be kept lower than 50 mg/d in the treatment of CD.

Original languageEnglish
Pages (from-to)160-166
Number of pages7
JournalAmerican Journal of Clinical Nutrition
Issue number1
Publication statusPublished - Jan 1 2007


  • Celiac disease
  • Gastroenterology
  • Gluten threshold in gluten-free food
  • Gluten toxicity
  • Gluten-free diet
  • Small-intestinal morphometry

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science


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