B-071 Unraveling Histamine Intolerance: Exploring DAO Quantity, Elimination Ratios and Cofactor Influences
Authors: Seidl H , Kellner K , Maier D 
Published: October 2024

Abstract

Background
Non-allergic reactions to food, often triggered by biogenic amines like histamine, result in symptoms such as headache, rhinitis, respiratory issues, digestive complaints, and eczema. The symptomatic overlap between histamine intolerance (HIT) and allergies may contribute to potential underdiagnosis. Limited data impedes precise incidence determination, but estimates suggest 1-3% of the population is affected, with increasing cases anticipated as knowledge and diagnostic tools for HIT advance. Despite histamine's physiological importance, elevated levels pose health risks. HIT arises when ingested or internally released histamine surpasses rapid breakdown capacity. Studies link HIT to DAO deficiency and/or impaired DAO activity, often in subgroups with genetic, pathological, or pharmacological factors. DAO cofactor deficiencies like copper, zinc, vitamin C or vitamin B6 may exacerbate DAO impairment. The trial aimed to explore the relationship of histamine elimination, DAO quantity, and essential cofactors for DAO activity.

Methods
Serum samples from 40 patients underwent analysis for DAO quantity and histamine elimination ratio using Immundiagnostik AG test kits. ELISA quantification employed a sandwich technique with polyclonal antibodies against recombinant DAO. Low DAO levels (&lt; 3 U/ml) indicated histamine intolerance, moderate levels (3 - 10 U/ml) suggested probability, and high levels (&lt; 10 U/ml) initially ruled out intolerance. Histamine elimination efficiency was assessed by comparing spiked sample levels at 0 and 24 hours after incubation, gauging histamine breakdown mechanisms without directly measuring enzyme quantity. Histamine elimination &gt; 40% indicated unlikely intolerance, 25 - 40% (moderate) suggested probability, and &lt; 25% (poor) indicated likelihood. Additionally, vitamin B6 influence was explored using Immundiagnostik AG's microbiological ID-VIT Test system, spiking samples with DAO for supplementation. Six samples with varying B6 levels underwent investigation.

Results
The investigation revealed that DAO quantity and histamine elimination highlight the enzyme's pivotal role. Distinctions emerged in histamine intolerance classification, with more than 25% of the population showing reduced elimination in samples with moderate DAO levels (3-10 U/mL), and more than 10% showing reduced elimination in samples with high DAO levels (&gt;10 U/mL), suggesting potential DAO inhibition contributing to impaired histamine breakdown. Analyses based on functional vitamin B6 levels demonstrated varying responses to DAO supplementation. Samples with high functional B6 levels (&gt;20 µg/l) showed a 20% increase in elimination with DAO supplementation of 3 U/mL. In contrast, samples with lower B6 levels (&lt;7 µg/l) exhibited minimal to no additional elimination, despite supplemental DAO at 6 U/mL. These findings underscore the nuanced interplay among DAO levels, histamine elimination, and the influence of vitamin B6, providing insights into factors impacting histamine metabolism across diverse patient profiles.

Conclusions
The data unveil a high potential for differential diagnosis, particularly in the realm of moderate to high DAO quantity, where the dependence on DAO inhibition yields a different classification of HIT probability. Analyzing DAO cofactors, such as vitamin B6, emerges as a valuable complementary tool for the diagnosis and treatment of HIT. These findings underscore the importance of considering DAO levels, their inhibition, and cofactors in a comprehensive approach to enhance the accuracy of HIT assessment and guide effective therapeutic interventions.