Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: a randomised, double-blind, placebo-controlled cross-over study

Wien Klin Wochenschr. 2011 Jan;123(1-2):15-20. doi: 10.1007/s00508-010-1506-y. Epub 2010 Dec 20.


Objectives: The term histamine intolerance stands for a range of symptoms involving various effector organs after the consumption of histamine-rich food. Our intention was to objectify and quantify histamine-associated symptoms and to analyse whether oral administration of the histamine-degrading enzyme diamine oxidase (DAO) caused a reduction of symptoms.

Patients and methods: Four Austrian centres participated. Patients suspected to be histamine intolerant were recruited. The first step consisted in the open oral provocation of these patients with 75 mg of liquid histamine. Patients who developed symptoms were tested in a randomised double blind crossover provocation protocol using histamine-containing and histamine-free tea in combination with DAO capsules or placebo. Main and secondary symptoms (strongest and weaker symptoms based on a ten-point scale) were defined, the grand total of all symptoms of the individual provocation steps was determined and changes in symptoms after administration of DAO were measured.

Results: Thirty nine patients reacted to the open histamine provocation and were enrolled in the blinded part. Here, both the main and secondary symptoms were not reproducible. Subjects reacted sometimes unexpectedly and randomly. Regarding the total symptom scores, the differences between the three treatment groups were statistically significant. The intake of DAO demonstrated a statistically significant reduction of histamine-associated symptoms compared to placebo (P = 0.014).

Conclusions: Oral provocation with 75 mg of liquid histamine failed to reproduce histamine-associated single symptoms in many patients. One may suggest that histamine-intolerant subjects reacted with different organs on different occasions. As a consequence, reproducibility of single symptoms alone may not be appropriate to diagnose histamine-intolerance whereas a global symptom score could be more appropriate. The fact, that the intake of DAO capsules compared to placebo led to a statistically significant reduction of total symptom scores, may indirectly point in the same direction.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Amine Oxidase (Copper-Containing) / administration & dosage*
  • Austria
  • Cross-Over Studies
  • Diagnostic Errors / prevention & control*
  • Double-Blind Method
  • Female
  • Food Hypersensitivity / diagnosis*
  • Food Hypersensitivity / drug therapy*
  • Food Hypersensitivity / etiology
  • Histamine / administration & dosage
  • Histamine / adverse effects*
  • Humans
  • Male
  • Placebo Effect
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Treatment Outcome


  • Histamine
  • Amine Oxidase (Copper-Containing)