Histamine Intolerance

DAO is continuously released into the bloodstream, and hence the activity of DAO in blood serum is a suitable marker for HIT diagnoses. Measuring the intracellular HNMT, which occurs primarily in the liver, is, on the contrary, not possible. Here, the detection of an activity-decreasing genetic HNMT variant is available. HIT is nevertheless not only caused by the insufficient breakdown of histamine. It may also manifest clinically when there is a histamine surplus that is currently not broken down sufficiently, even under normal DOA activity. Allergic diseases, such as hay fever, sensitisation towards mould, and elevated levels of mast cell activity are sources of additional histamine that accumulates with ingested histamine. In order to diagnose this type of transgression of the individual histamine tolerance limit, DAO activity should be analysed together with the histamine total in blood.

In order to avoid unnecessary lifelong dieting, whether the existing lack of DAO is caused by a genetic primary, or a secondary condition, must be analysed. The result will then have an impact on the treatment. A primary lack of DAO is accompanied by decreased DAO activity, due to genetic variations (polymorphisms). Patients with proven decreased DAO activity in blood and corresponding clinical symptoms ought to receive genetic screening, in order to differentiate between a genetic or secondary, and therefore causally treatable and reversible, form of histamine intolerance.

A common cause for a secondary lack of DAO are inflammatory or degenerative bowel diseases, because more than 90 % of DAO is produced in the intestinal epithelium. But also cases in which drugs, alcohol or toxins decrease the activity of DAO, are considered secondary forms. Drugs that have a proven record of decreasing DAO activity are mentioned below. Another possible cause for decreased DAO activity may be a copper deficiency, since copper constitutes DAO’s central atom and is hence vital for its performance.

When decreased DAO activity or significantly elevated histamine levels are proven, foods rich in histamine have to be avoided. In the case of a secondary HIT, meaning a decreased DAO activity despite normal genetic makeup, the cause has to be identified (chronic inflammatory bowel disease? copper deficiency? prescription drug and alcohol history?), since secondary histamine intolerance is, unlike primary histamine intolerance, in most cases reversible. In patients with decreased DAO activity, copper levels should be monitored, in order to avoid an additional deterioration of the residual DAO activity due to copper deficiency. Simultaneously, zinc levels should be monitored, since zinc inhibits intestinal copper absorption. A merely symptomatic therapy through the prescription of H1 receptor antagonists should only be a temporary measure.

Known DAO-inhibiting drugs:

While Symptoms of a lack of DAO are often periodical, symptoms of HNMT deficiency occur immediately after meals, for example. In the case of dysfunctional HNMT, especially the brain, bronchial mucosa and liver are affected. Patients with normal DAO levels, who experience only slow deterioration (days) of symptoms after dietary errors and in which after dieting properly symptoms abate only slowly, may suffer from HNMT deficiency. Testing the activity of this intracellular enzyme is not possible. Diagnostics are done via testing for a genetic variant (C314T) that decreases HNMT activity by 30-50 %. This genetic variant is associated with histamine-related diseases, such as asthma and atopic dermatitis. Additionally, drugs are known to be HNMT inhibitors. Amodiaquine, Metoprine, Tacrine and Diphenhydramine (H1-antihistamine!) block HNMT’s histamine binding sites. Carriers of C314T-polymorphisms should hence avoid HNMT blockers as well as histamine liberators.

DAO activity: 2 ml serum
Histamine tot.: in blood: 10 ml heparin blood
For both tests, a sample receipt within 24 hrs has to be ensured. The sample should be stored and transported at room temperature. Within the Berlin city area, we offer a courier service (+49 (0)30 7701- 250). For collections beyond Berlin, please contact our complimentary courier service (+49 (0)30 77001-450).

DAO genetic testing and/or HNMT genetic testing:
2 ml EDTA blood
For genetic testing, the patient’s declaration of consent is mandatory. Transport to the laboratory is not time-sensitive and can be sent by mail.

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