New Guidelines For Diagnosing Histamine Intolerance
The new guidelines for diagnosing histamine intolerance provides an interesting overview as to some of the challenges that researcher and patients share.[1]
The question they pose is not whether histamine intolerance exists but what is the root cause? Is it actually what we eat?
They then go on to propose new guidelines for diagnosing and managing histamine intolerance.
The following is a summary of their findings and recommendations.
Why it may not be just about the food
The scientific studies demonstrating a direct link between eating histamine foods and adverse reactions is limited.
A German study of children with chronic abdominal pain concluded that, although 50% responded to a low histamine diet, only one responded with a histamine loading challenge. [2]
This suggests that there may be different mechanisms at play – one where ingested histamine is the root cause, and another where it is more a symptom of another root cause.
Why it may not be just about DAO Deficiency
No scientific studies currently demonstrate the direct link between eating high histamine foods and DAO deficiency.
Instead, the intake of the histamine-degrading enzyme DAO was found to reduce symptoms irrespective of whether or not histamine was ingested. [3]
It is worth noting that some practitioners even use high dose DAO supplementation (2 before, 2 during, and 2 after) a meal for mast cell activation disorder.
Another study demonstrated the reduction in DAO activity in the colonic mucosa of patients with food allergies was inconsequential. Rather it was the histamine N-methyl-transferase (HNMT) activity that was diminished, in proportion to elevated histamine in the intestinal mucosa, which was merely hypothesized to be due to mast-cell release in the colon. [4]
These findings raise unanswered questions of the relative importance of DAO and HNMT.
Why Current Tests Are Unreliable
All current tests look at histamine levels at one point in time. They do not test for levels before and after eating high histamine foods. Therefore no test can currently confirm or deny a link between histamine intolerance and ingested food.
Furthermore, the available tests have significant problems. Specifically:
DAO in serum – is not conclusive, as DAO levels are not concentrated in the bloodstream. [5, 6, 7, 8] The ideal would be to have a test that shows DAO enzyme levels in the intestine or colonic mucosa but no such test is readily available.
Histamine in stool – intestinal bacteria can produce large amounts of histamine such that it does not reflect ingested histamine or enzyme sufficiency.
Histamine in plasma – does not correlate with histamine or histamine intolerance symptoms. [9] Functional practitioners also tend to use this more as a methylation marker.
Methyl-histamine in urine – the level depends not only on histamine but also the protein content of foods. HNMT rises on a high protein but low histamine diet. [10]
Histamine Skin-Prick Test – skin prick tests do not link to either enzymes or the ingestion of high histamine foods.
The authors do not recommend any of the above tests to diagnose histamine intolerance.
Although the authors do not address it, it should also be stated that 23andMe is also not a reliable method of diagnosing histamine intolerance as it merely shows the possibility of an error rather than the error actually occurring.
What Are We Missing?
The issue is not whether certain individuals respond to a low histamine diet or even DAO supplements. The issue is that in the vast majority of cases these appear not to be the root cause. Rather
“The so-called histamine intolerance is more likely a “complex of symptoms that can be attributed to histamine only in individual cases” than an isolated clinical picture exclusively triggered by ingested histamine.”
The researchers raise the hypothesis that the ‘missing link’ may be more related to internal environmental factors. Specifically:
- Small Intestinal Permeability.
- Intestinal disorders (especially inflammatory ones, and in my experience small intestinal bacterial overgrowth).
- Hormone status.
- The composition of intestinal flora (especially in my experience histamine or amine secreting bacterial infections).
- Food selection, meal composition, and the interval between meals.
Alcohol, certain medications, and other biogenic amines are also strongly thought to play a role.
Recommended Guidelines
Against all this uncertainty, the German recommendations are to do a limited time elimination diet, with a histamine challenge, to diagnose histamine intolerance.
Dietary Recommendations
The recommendations in relation to diet are to follow an elimination diet for the two week test period only. Then to gradually reintroduce foods as follows:

Their experience shows that intolerances can be slowly increased beyond the low histamine threshold.
This is also my experience. In most histamine-sensitive people are eventually able to tolerate any amount of low histamine foods, 1 serve of moderate histamine foods, or a tablespoon of high histamine foods daily. Very high histamine foods are tolerated rarely (if at all).
When low histamine foods are not tolerated then it is important to be open to other or additional root causes.
Histamine Intolerance Food Lists
The authors acknowledge the overriding problem with histamine intolerance food lists – that the histamine content of foods varies widely dependent on storage, transportation, and processing.
Nevertheless, they point out a number of common mistakes.
Firstly, that many lists focus on histamine to the exclusion of other amines (which compete with histamine for degradation). [11]
Secondly, of the “mast cell creep” on food lists, including mast cell degranulating foods. I would also add to this the misconception that anti-inflammatory foods raise histamine tolerance.
Antihistamine Use
The recommendation is to use H1 antihistamines for flushing, and H2 blockers for nausea and vomiting for acute episodes only. Some practitioners use both together for an enhanced effect.
Other Comments
I would like to conclude with a few comments in relation to my own experience as a practitioner.
Within my practice, I estimate that around 70% of my clients, end up tracing their histamine intolerance back to a gastro-intestinal issue. Once treated their histamine tolerance often increases dramatically.
I wholly concur with the author’s view that the missing link could well be internal environmental factors.
I disagree slightly with the diagnostic guidelines seeing the gastrointestinal status as only being explored if the histamine challenge is failed. I am not sure this is proven. From a purely practical perspective, I see this as a gray overlapping area.
For this reason, if you can only afford to run one test only then please consider running the GI-Map test on its own or in conjunction with the Para- wellness Research Test. The Para-wellness test on its own is not sufficient as it does not test for bacterial infections. In my experience, other well-known gut tests only pick up a 10% or so of what is actually going on.
The authors have identified a number of areas that need research. In the meantime, a lot can be achieved by optimizing overall health.
Sources
[8] Jarisch R. Leserbrief. Allergologie. 2009;32:41–2.
[11] Häberle M. Biogene Amine – Klinische und lebens mittel chemische Aspekte. Zentralbl Haut. 1987;153:157–168.
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