New Guidelines For Diagnosing Histamine Intolerance

April 23, 2017  |  Blog, 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.

Histamine Intolerance Diagnosis

 

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:

Histamine Intolerance Elimination Diet

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

[1] Reese, Imke et al. “German guideline for the management of adverse reactions to ingested histamine.” Allergo Journal International 26.2 (2017): 72-79.

[2] Hoffmann KM, Gruber E, Deutschmann A, Jahnel J, Hauer AC. Histamine intolerance in children with chronic abdominal pain. Arch Dis Child. 2013;98:832–833.

[3]  Komericki P, Klein G, Reider N, Hawranek T, Strimitzer T, Lang R, et al. Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: a randomized, double-blind, placebo-controlled crossover study. Wien Klin Wochenschr. 2011;123:15–20.

[ 4] Kuefner MA, Schwelberger HG, Weidenhiller M, Hahn EG, Raithel M. Both catabolic pathways of histamine via histamine-N-methyltransferase and diamine oxidase are diminished in the colonic mucosa of patients with food allergy. InflammRes. 2004;53(Suppl 1):S31–S32.

[5] Töndury B, Wüthrich B, Schmid-Grendelmeier P, Seifert B, Ballmer-Weber B. Histaminintoleranz: Wie sinnvollist die Bestimmung der Diaminoxidase-Aktivität im Serum in der alltäglichen klinischen Praxis? Allergologie. 2008;31:350–6.

[6] Kofler H, Aberer W, Deibl M, Hawranek TH, Klein G, Reider N, Fellner N. Diamine oxidase (DAO) serum activity: not a useful marker for diagnosis of histamine intolerance. Allergologie. 2009;32:105–9.

[7] Schwelberger HG, Feurle J, Houen G. New tools for studying old questions: antibodies for human diamine oxidase. J Neural Transm (Vienna). 2013;120:1019–26. 10.

[8] Jarisch R. Leserbrief. Allergologie. 2009;32:41–2.

[9] Giera B, Straube S, Konturek P, Hahn EG, Raithel M. Plasma histamine levels and symptoms in a double blind placebo controlled histamine provocation. Inflamm Res. 2008;57(Suppl 1):S73–S74.

[10] Keyzer JJ, Breukelman H, Wolthers BG, van den Heuvel M, Kromme N, Berg WC. Urinary excretion of histamine and some of its metabolites in man: influence of the diet. Agents Actions. 1984;15:189–94.

[11] Häberle M. Biogene Amine – Klinische und lebens mittel chemische Aspekte. Zentralbl Haut. 1987;153:157–168.

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  • Mimi Kelly Johnson

    Allison this is great and thanks for your work. i mentioned GI Map to a US practitioner and he said he had looked into it a few years back but it was still being validated. Has it been? Can you say more about your experiences treating based on this? Also as I have Interstitial Cystitis I am super sensitive to most supplements (The IC started after I took antibiotics for dental work). I am sure I do have mild SIBO and histamine intolerance but how do you treat GUT INFECTIONS and SIBO with really sensitive patients that detox through their bladders and just have poor detox generally (I also am being treated for CIRS) THANKS!

    • Hi Mimi – ill have to be brief. In my experience, it is the gold standard. I now am running it with all my clients, and repeatedly picking up issues. When treated those issues are providing rapid relief. IC is a hallmark of mold exposure. I treat in a specific order (if you treat out of order then you get into trouble) and choose the best-tolerated substance. In my opinion, it is difficult to resolve mold if viral/parasite issues are also in play for example. It is also important to ensure that the body is supported before detoxificaiton.

      • Mimi Kelly Johnson

        Hi Alison, thank you for the prompt reply! I will try to work in a consult with you soon, finances permitting. As you know all this takes a big financial toll!

  • Ross

    Alison can iodine cause an increase in histamine or mast cell degranulation?

    • Iodine contrast is known to be poorly tolerated (see maintz and novack)

  • Please consider getting the GI-Map gut test and working with someone who can address what is happening in the gut. I do not believe that the primary issue is genetics. Whilst this is a vulnerability perhaps this is not the solution. I believe regardless of genetics, with gut issues, that solutions are found in the gut.

  • Shelley Peers

    Hi Allison, I am new to exploring histamine intolerance. The two tests you mentioned above are US tests sites. Where should I go in Australia?

    • Both are able to be accessed in Australia. The Parawellness ships to Australia – and has standard postage returns. The Gi-Map is available through Invivo clinical in the UK (they have the Australian rights). The test has to be back at the lab within 3 days via Fedex which costs about $90. It means a person has to be within access of a fedex depot which they will be if near a major city. Unfortunately, there are no other tests available in Australia itself, that come even close in my opinion.

      • Shelley Peers

        Thank you Alison. Are tests vital or can we just make changes based on observations xx

        • VITAL. my practice of full of clients who have been guessing or had practitioners observing and guessing. They have spend thousands of dollars on supplements when some tests as cheap as $40 would have resolved the issue. I could rant on but you get the idea.

  • It has not been researched so I do not believe there is a proven answer. Perhaps the biggest downfall is using it as a bandaid as opposed to finding the route cause. DAO can be a measure of intestinal issues not a fixed non static genetic condition.

    • Jo

      Thank you Alison. My son (8yo) received a booster varicella vaccine over a year ago and since then has seemingly become histamine intolerant. It’s as if one week he could eat anything, in whatever quantity, and three days after receiving the shot, he had a big histamine reaction to orange juice (cramps, vomiting, puffy eyes) and since then his level of histamine tolerance has never been the same again. I can no longer give things like him yogurt, bolognaise and cheese on the same day without seeing at least a mild histamine reaction.
      It seems odd that his DAO levels could drop so suddenly? Could his mast cells have been hyper activated due to the vaccine and can’t switch off?? I feel so guilty now, that one vaccine has doomed him to a life on a low-histamine diet… Do over-active mast cells ever settle down on their own?

      • mary ann o brien

        Dear Alison
        Thank u for all of your excellent information on your site My daughter is very unwell for last 2 years following gardasil vaccine and seemingly has become histamine intolerant, Advocados (which were her favourite food) now make her throat and lips itch like crazy. Also raw spinach, dairy and other foods cause her face cheeks and around eys to swelll and large anrgy red blobs of a rash appear and eventually go. Can I assume that the vaccine has hyper activated her mast cells? Before vaccine she had no problems with any food or any allergies. Very desperate to find way forward as at 16 she has hardly been out of bed for two years. Many thanks in advance Mary Ann

        • In many instances, histamine intolerance results from an over-stimulation of the immune system. The way forward is to reduce the stressors (heavy metals, viruses, pathogens , stress etc) and improve the body’s vital reserves. I dont know what is right for your daughter. You may wish to find a functional health practitioner and work with them. It is possible to get significant improvements.

          • Jo

            Hi Alison,
            Thanks for your tips. I understand you don’t work with children so am wondering if you could please suggest any functional medical practitioners you may know of in Sydney who treat histamine intolerance. The one we see now is great, but specialises in autistic children.
            Thanks,
            Jo

          • I am sorry but I am not aware of anyone – I have a lot of functional practitioners refer histamine intolerant people to me. As you may be aware the RPA Allergy Unit does low histamine dietary advice. I hope that helps.