Non-responsive celiac disease may coincide with additional food intolerance/malabsorption, including histamine intolerance

Med Hypotheses. 2021 Jan:146:110404. doi: 10.1016/j.mehy.2020.110404. Epub 2020 Nov 21.


Background and pilot study: Celiac disease (CD) or gluten malabsorption is a well-defined autoimmune disorder characterized by mucosal gastrointestinal reaction to ingested gluten proteins. The necessary treatment for CD is a gluten-free diet. However, up to 30% of celiac patients experience persistent or recurring abdominal complaints despite following an exact gluten-free diet. This condition was named refractory, non-responsive celiac disease. Other food ingredients, such as carbohydrates and biogenic amines, also influence and impair digestion, and may cause these abdominal symptoms. In this retrospective pilot study, we have reported on 20 non-responsive, celiac disease patients, with persistent abdominal complaints, for longer than 6 months. These patients were evaluated for extra food intolerance/malabsorption, including fructose malabsorption, histamine-, lactose intolerance, and Helicobacter pylori (H.p.) infection.

Results and conclusions: The results demonstrate that 18 of the 20 refractory, non-responsive celiac disease patients presented various, additional food intolerance/malabsorption and/or H.p. infection. Seven NRCD patients demonstrated lactose intolerance, 7 showed fructose malabsorption, 11 had additional histamine intolerance and 6 had signs of H.p. infection or combinations thereof. If present, then eradication of H.p. was performed. Histamine intolerance, was found in more than 50% of patients, and it seems to play an important role in non-responsive celiac disease. A registered dietician continued to help with, and to improve, the patients' gluten-free diet. Furthermore, additional food intolerance/malabsorption considerations were included in the individual, dietary recommendations.

Keywords: Celiac disease; Fructose malabsorption; Gluten sensitivity; Histamine intolerance; Lactose intolerance.

MeSH terms

  • Celiac Disease* / complications
  • Food Intolerance
  • Glutens
  • Histamine*
  • Humans
  • Pilot Projects
  • Retrospective Studies


  • Glutens
  • Histamine