Histamine intolerance: fact or fiction?

Published: August 28, 2023

Histamine intolerance (HIT) is a disorder postulated to involve an increased sensitivity to dietary histamine. Food histamine content increases by maturing and fermentation processes and histamine is present in a wide range of foods in highly variable concentrations. When ingested, the main enzyme for degradation of histamine is the diaminoxidase (DAO). A reduced DAO activity and thereby resulting high histamine levels are suspected to be the cause of HIT. Patients report typical symptoms such as diarrhea, flushing, urticaria, pruritus, headache, hypotension, arrhythmias, and asthma after ingestion of histamine-rich food. A prevalence of up to 1-3% of the population has been proposed, but never scientifically substantiated.

In a recent issue of The Journal of Allergy and Clinical Immunology: In Practice, Bent and colleagues published a study of 59 patients with histories of HIT after eating histamine-rich food. They performed single-masked, placebo-controlled histamine challenges and correlated the results with history and clinical data, including serum DAO. Patients were predominantly middle-aged females. Histamine provocation was safe; only one patient required antihistamine treatment. Nearly two thirds of patients reported symptoms to placebo indicating possible anxiety with conditioning rather than true hypersensitivity. HIT was clearly excluded in 85% of patients. The rest of the patients either had objective symptoms only after histamine or stronger reactions to histamine than to placebo. These patients had low DAO activity, however overlapping with non-HIT patients in whom the activity was very variable.

The authors concluded that challenges appeared safe and that placebo-controlled testing is needed as placebo reactions were frequent. In the majority of patients with a suspicion of HIT, the diagnosis was ruled out. In the remainder, reactions by chance could not be excluded. High DAO levels may exclude HIT, whereas low levels are quite common and not diagnostic for HIT.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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