November 09, 2014 9:00 pm


A new study by Maintz and Novak reveals that diamine oxidase alone does not explain histamine intolerance.

Previously, genetic mutations in diamine oxidase were thought to be the sole cause. However, this research suggests a more complex story.

The findings in this new study are as follows:

Diamine Oxidase: The Enzyme That Degrades Histamine

Histamine intolerance results from an imbalance between histamine and the body’s ability to degrade it.

Specifically, there are two primary enzymes responsible for this degradation: diamine oxidase, which regulates histamine extracellularly, and histamine-N-methyltransferase, which regulates it intracellularly. 

When one or both of these enzymes become defective, histamine accumulates in the body.

Decoding Histamine Intolerance: A Genetic Study

Maintz and Novak conducted a study involving 285 patients with histamine intolerance and 199 healthy individuals to evaluate whether diamine oxidase gene variations could explain histamine intolerance.

Additionally, they aimed to determine whether these genetic variations were associated with decreased or increased activity.

The significant results are as follows:

Diamine Oxidase Activity: A Factor in Histamine Intolerance

Diamine oxidase activity varies significantly among the general population. 

Participants with histamine intolerance are more likely to have reduced activity levels, with 50% of these showing lower levels compared to 17% of healthy controls. 

Furthermore, those with reduced levels are more likely to exhibit symptoms of histamine intolerance.

 However, it is essential to note that this was not an absolute correlation, as not everyone with histamine intolerance had reduced diamine oxidase activity.

histamine intolerance, genetics, diamine oxidase, DAO, Alison Vickery, Health, Australia

Genetic Insights: Variations In Activity and Histamine Intolerance

The study identified five SNPs that significantly influence diamine oxidase activity. 

Four SNPs—rs2052129, rs2268999, rs10156191, and rs1049742—are linked to reduced activity, while the fifth, rs1049748, is linked to increased activity. 

However, these mutations do not directly cause histamine intolerance. 

These SNPs frequently appear in both the healthy population and those with histamine intolerance. 

Therefore, having one of these four mutations does not necessarily increase the likelihood of suffering from histamine intolerance.


Genetic variations are definitively responsible for differences in diamine oxidase activity, with some variations increasing it while others decrease it.

However, diamine oxidase activity alone does not cause histamine intolerance. In fact, half of the participants with histamine intolerance don’t have reduced levels.

Maintz and Novak et al. conclude that a complex interaction exists between environmental factors (such as pathogens, medications, or alcohol) and other associated genetic defects must be at play.

This conclusion strongly correlates with my clinical experience. 

Through testing hundreds of people, I have developed a detailed understanding of the environmental factors linked to histamine intolerance and mast cell activation.  By removing environmental factors that cause the body to release histamine, health can be restored. 

To explore what medications cause histamine intolerance, for example, read my blog post Medicines That Cause Histamine Intolerance. 

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