The new guidelines for diagnosing histamine intolerance provide a fascinating overview of some challenges that researchers and patients share.
The question they pose is not whether histamine intolerance exists but what is the root cause. Is it actually what we eat?
They then 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 are 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.
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 diamine oxidase (DAO) deficiency.
Instead, the intake of the histamine-degrading enzyme DAO was found to reduce symptoms irrespective of whether or not histamine was ingested.
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. Instead, the histamine N-methyl-transferase (HNMT) activity 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.
These findings raise unanswered questions about 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 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. 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 that do not reflect ingested histamine or enzyme sufficiency.
Histamine in plasma – does not correlate with histamine or histamine intolerance symptoms. 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 on the protein content of foods. HNMT rises on a high protein but low histamine diet. 
Histamine Skin-Prick Test – skin prick tests do not link to enzymes or high histamine foods ingestion.
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 occurring.
What Are We Missing?
The issue is not whether specific individuals respond to a low histamine diet or even DAO supplements. The issue is that, in most 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 hypothesize that the ‘missing link’ may be more related to internal environmental factors. Specifically:
Small Intestinal Permeability.
Intestinal disorders (especially inflammatory ones).
The composition of intestinal flora.
Food selection, meal composition, and the interval between meals.
Alcohol, certain medications, and other biogenic amines are also strongly thought to play a role.
Against all this uncertainty, the German recommends a limited-time elimination diet with a histamine challenge to diagnose histamine intolerance.
The recommendations about diet are to follow an elimination diet for the two-week test period only. Then gradually reintroduce foods.
Their experience shows that intolerances can slowly increase beyond the low histamine threshold.
This is also my experience. Most histamine-sensitive people can eventually tolerate any amount of low histamine foods, 1 serving 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, it is essential 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 foods’ histamine content varies widely depending on storage, transportation, and processing.
Nevertheless, they point out several common mistakes.
Firstly, many lists focus on histamine to exclude other amines (which compete with histamine for degradation).
Secondly, the “mast cell creep” on food lists, including mast cell degranulating foods. I would also add to the misconception that anti-inflammatory foods raise histamine tolerance.
The recommendation is to use H1 antihistamines for flushing and H2 blockers for nausea and vomiting for acute episodes. Some practitioners use both together for an enhanced effect.
I would like to conclude with a few comments about my experience as a practitioner.
I have been working in the area of histamine intolerance and mast cell activation for well over a decade. I have reversed histamine intolerance and mast cell activation in hundreds of people.
I believe that the vast majority (if not all) of histamine intolerance and mast cell activation has a root cause. With that root cause happening on a spectrum of leaky gut, auto-immunity, and a blocked autonomic nervous system.
If you want to learn more about what hundreds of clients have taught me and how to restore health, please take my FREE Course on The Roadmap to Resolution.
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