Letzte Aktualisierung am 11. December 2023 von Dr. Michael Zechmann-Khreis
Correct diagnosis of histamine intolerance
Is there a “histamine intolerance test”? How histamine intolerance (HIT) is diagnosed has changed continuously in recent years. As histamine intolerance is a relatively new diagnosis, studies first had to be carried out and experience gathered. There is currently a guideline that sets the gold standard in diagnostics. In the following article, we also show you various historical diagnostic methods and their problems.
But first we need to clarify a few terms:
Some terms and explanations
Diamine oxidase (DAO) is an enzyme that is produced in the small intestine, among other places, and breaks down histamine ingested with food. The DAO requires vitamin B6 and copper, among other things, for this process. DAO is inhibited by certain substances such as alcohol or other biogenic amines. Histamine is formed naturally by bacteria, i.e. food that has been stored for a long time contains more histamine than fresh food. Intestinal bacteria also produce histamine and other biogenic amines. Our body therefore needs this enzyme in the intestine to break down the histamine that is absorbed and produced in the intestine.
Histamine N-methyl transferase (HNMT) is an enzyme that is found in cells, primarily in liver cells, but also in the intestine. HNMT also breaks down histamine.
How is histamine intolerance diagnosed?
There is now a guideline that is recommended by leading professional organizations. It is important not to self-diagnose, but to always come to a diagnosis in dialog with the doctor. The following diagnostic method is currently considered the gold standard:
First step: Symptom diary and differential diagnosis
Before going to the doctor, you should always keep a symptom diary . This makes it much easier for the attending physician to narrow down the symptoms.
While you are keeping a symptom diary, you should eat normally and not go on a diet or suddenly give up certain products. Your doctor must take time for you and have a very intensive discussion with you. It is best if you bring your nutrition / symptom diary with you. Also make a note of your menstrual cycle and any medication you take in your diary! Also note the symptoms you have. There are very good forms in book form.
Your doctor will try to rule out other illnesses by means of a differential diagnosis. These include, for example, allergies, mastocytosis, chronic inflammatory bowel disease or other intolerances. Differential diagnosis means that other diseases with very similar symptoms are ruled out first. Allergies e.g. via Prick and RAST test, intestinal fructose intolerance or lactose intolerance via H2 breath test. There are a few other diseases, for example the very rare mastocytosis, which should be ruled out first.
Second step: elimination diet with or without provocation test
As this diagnostic route requires precise knowledge of the histamine content and histamine tolerance, this diagnostic route is very difficult and must be accompanied by nutritional therapy!
The first step is to go through a well-planned and, ideally, dietary supervised elimination diet, including a very precise food and symptom diary. This phase lasts 2-4 weeks. During the fasting period, all foods containing biogenic amines are avoided, no alcohol is consumed, no DAO-blocking medication is taken (discuss with your doctor!) and no antihistamines are taken.
If there is an improvement in symptoms, HIT is very likely after exclusion of other possible diseases by differential diagnosis.
If the result is positive, your doctor should have copper and vitamin B6 tested in a blood test, as the DAO needs these substances to function properly. If there are too few of them, the DAO cannot be formed or cannot function properly. Substitution can then significantly improve the HIT.
Third step: provocation test
Now, after this waiting period, a provocation test can be carried out, which should ideally be placebo-controlled and double-blind. You are given various liquids to drink and the reactions are recorded. However, this is probably only possible in specialist clinics and is not recommended by some guidelines, or is explicitly discouraged. Alternatively, you can (in consultation with your doctor!) eat foods containing histamine and record your reactions to them in a diary. It is important to test only 1 food every day! For example, mountain cheese, red wine or sauerkraut. The reactions should then occur within 4 hours. In the case of a severe form of histamine intolerance (which is very rare!), an anaphylactic shock could occur during the provocation test, which is why it is better not to do this without medical supervision.
This step is usually no longer necessary for the diagnosis of histamine intolerance, as the diagnosis is usually already clear after step two.
Methods no longer recommended
Caution: There are still blood home tests or other home tests for histamine intolerance diagnostics on the market. Some doctors still carry out blood tests to determine the DAO. However, these tests are not considered suitable by the specialist organizations for the reasons outlined above and can lead to misdiagnoses. Unfortunately, there is no histamine test that provides a diagnosis by taking a blood sample.
Diagnostic method: Histamine test for blood
Since we have the enzymes DAO and HNMT for degradation, one could assume that the amount of enzymes in the blood could be used as a diagnostic method. Unfortunately, this does not work. Attempts have also been made to establish the activity of the DAO, i.e. not the quantity, as a diagnostic factor. Also with moderate success. It has been found that the activity of the enzymes in the mucous membrane of the small intestine is not related to the quantity or activity in the blood. A histamine test of this type is available to buy, but it does not provide valid results.
Diagnostic pathway: small intestine biopsy DAO activity
Alternatively, the activity can be determined via a small intestine biopsy using an ELISA(enzyme-linked immunosorbent assay). The latter is recommended if a biopsy of the small intestine is already being performed anyway. Therefore, this method is not a common diagnostic method. Although this histamine test works, it is rarely used because the interpretation of DAO activity must also be carried out in the context of the clinic and the medical history. This means that the gold standard described above must be followed anyway.
Diagnostic pathway: laboratory parameters “urine” and “stool”
Histamine test with urine
It is also possible to determine the histamine and methylhistamine concentration in the urine. Mehylhistamine is the degradation product of HNMT. If there is a DAO deficiency, histamine is increasingly broken down in the cells via the HNMT. The degradation product methylhistamine, which is excreted in the urine and can therefore be determined by a laboratory using a 12-hour urine collection test, increases accordingly. A strict potato-rice diet is then followed for a few days and the urine test is repeated. The change in the results was thought to indicate a histamine intolerance. That turned out not to be the case. A differential diagnosis is also important with this histamine test, as this test alone is not conclusive enough to diagnose a histamine intolerance. 5)
Histamine test with stool sample
The amount of histamine can also be determined in the stool. However, this amount only indicates how much histamine has not been broken down in the intestine. This amount varies depending on what you have eaten beforehand, i.e. depending on the amount of histamine you have ingested and the bacterial composition in your gut. This test cannot take into account the histamine produced by the body itself. This test has long been considered unsafe and is therefore an outdated and invalid diagnostic method. 5)
This means that measurements of DAO or histamine via urine or stool have not proven to be meaningful. As things currently stand, this leaves only a purely clinical diagnosis (see above) for histamine intolerance, as there are (as yet) no reliable laboratory parameters.
Other histamine tests
The IgG test measures the immune reaction of the body’s own immunoglobulin G. These tests are definitely not suitable for detecting lactose intolerance, fructose malabsorption or histamine intolerance! Other tests offered on the market must also be classified as dubious. There are no studies or evaluations for most of these tests, even if they sound very scientific and the manufacturers advertise with positive examples.
Tests reported to us by affected persons but not suitable for the diagnosis of histamine intolerance:
Status April 2019
- Hair analysis
- Saliva test
- TCM test / kinesiology procedure
- IgG4 tests (mostly with blood collection at home; these tests are very heavily advertised)
- Facial diagnosis
- Tongue diagnosis
- Laying on of hands
- Blood home test
1) Buchart, K. “Gut leben mit Nahrungsmittelallergien”, Löwenzahn Verlag, 2008, after personal communication with Jarisch, 2002
2) Jarisch, R. “Food intolerance”, medmix 4/2008, pp 49-52
3) Vogelreuter, A. “Food intolerances”, Wissenschaftliche Verlagsgesellschaft Stuttgart, 2012
4) Masterman, G. “What HIT me? Living with Histamine Intolerance“,2nd edition, 2013
5) Jarisch, R.“Histaminintoleranz – Histamin und Seekrankheit“, Thieme, 3rd edition 2013
6) Mayer I, Missbichler A, Wantke, et.al. “Optimized radioextraction assay for the quantitative determination of diamine oxidase (DAO) activity in human serum and plasma”, Allergologie, Jahrgang 28, 1/2005, 1-8
7) Reese et al: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergology and Environmental Medicine (GPA) and the Medical Association of German Allergists (ÄDA), 2012