Histamine is indispensable for the human body since it fulfils vital functions. It is both produced in the body and taken in with food in various quantities. Problems only occur in case of excessive quantities or not degraded histamine. In these cases, histamine will lead to allergic and pseudoallergic reactions.
Histamine intolerance is due to a (temporary) deficiency or an inhibition of the enzyme diamine oxidase (DAO). DAO is the enzyme responsible for the degradation of histamine. Although DAO is virtually found in the whole body, the bowels constitute its most important site of action. The enzymatic activity of DAO determines the rate of degradation of histamine. If a DAO deficiency and / or inhibition is present, the organism will not be able to degrade quickly enough the histamine taken in with food or released from body cells and the symptoms of histamine intolerance will occur.
Millions of people suffer from considerable complaints after having eaten certain foodstuffs:
An excessive quantity of histamine in the body may be responsible for these complex complaints. Another cause of a reduced DAO function is the taking of substances inhibiting its activity such as alcohol or drugs.
Histamine-induced food intolerance is not mediated by IgE. Determining the DAO activity in the serum therefore is the suitable marker for diagnosing histamine intolerance and associated clinical pictures.
Histamine intolerance, also called histamine incompatibility, can be detected beyond doubt by means of a blood test.
In-vitro diagnostic procedure for quantitative determination of diamine oxidase activity in the serum
The test is based on a radio immuno assay (RIA) principle. The determination of the DAO activity is achieved by determining the concentration of a reaction product. Radiolabelled putrescine is used as substrate. The reaction product is radioactive 1-pyrroline that is transferred into an organic solvent by means of liquid phase extraction. After adding scintillator, radioactivity is determined by a beta counter. The quantity of radioactivity measured is directly proportional to the DAO activity of the sample.
In case of histamine intolerance, the body cannot or can only partially degrade histamine. This is caused by a (temporary) deficiency or an inhibition of the diamine oxidase (DAO). According to the findings available up to now, in most instances, histamine intolerance is not a genetic, but an acquired disease that is manifest in approx. three per cent of the population. In up to 20%, symptoms occur in particular when foodstuffs rich in histamine are consumed together with DAO inhibitors such as alcohol. Approximately 80 per cent of the persons affected are women, most of them aged 40 and over. The risk of developing this intolerance is increased for persons who suffer from inflammatory intestinal diseases or cross sensitivities.
Histamine is a very active mediator for a large number of physical reactions and as such is regulated very well. DAO is the most important regulator for the histamine present in the tissue and in the blood circulation. Depending on the current requirements in the organism, the enzyme converts the histamine present in the tissue or in the blood circulation into imidazole acetaldehyde, a substance that does not trigger any action in the organism. This ensures a steady histamine level required for the balance of the countless chemical reactions taking place in the body.
Histamine is the most important representative of a class of substances combined under the name of biogenous amines. This is a large number of – in most cases aliphatic – polyamines (saturated organic compounds comprising several amino groups) that are found in nearly all living organisms as natural metabolic products. Polyamines have essential regulatory properties for cellular growth and cell division. Furthermore, they are highly reactive mediators of a large number of metabolic processes – in very small concentrations already. In nerve cells and other excitable cells, among other things, polyamines play an essential role as neurotransmitters for the regulation of the synaptic activity and the regeneration of cells.
Complaints basically develop due to an excessive quantity of histamine in the organism. The activity of DAO is limited; histamine taken in through food and produced in the body cannot be degraded at all or only to a limited extent.
Biosynthesis and degradation of histamine
There are various reasons that can lead to the development of histamine intolerance:
Consumption of foodstuffs rich in histamine
||After the consumption, the histamine concentration in the blood will increase. In particular foodstuffs that ripen for a very (too) long time or that are stored for a very (too) long time, have a high content of histamine that may cause problems depending on DAO activity.|
Consumption of biogenous amines & histamine liberators
||In case of a high consumption of biogenous amines, DAO is no longer available in sufficient quantities for the degradation of histamine. Other foodstuffs, so-called histamine liberators, can release the body’s histamine and thus have a negative influence on the histamine level in the body.|
Inhibition of the enzyme
||The inhibition of the DAO enzyme results in histamine intolerance. Possible potent inhibitors of DAO are in particular alcohol, but also some common drugs.|
Affected intestinal flora
|An affected intestinal flora produces considerable quantities of histamine and other biogenous amines that lead to an additional inhibition of DAO.|
Vitamin B6 and copper deficiency
|Copper is a central component of DAO. A deficiency of copper results in not enough DAO being produced. Vitamin B6 is a co-factor of DAO. Without vitamin B6, the enzyme is not able to degrade histamine.|
Congenital deficiency of DAO
|This very rare type of histamine intolerance is based on a congenital enzyme defect due to which the enzyme is not produced in sufficient quantities.|
The histamine intolerance test measures the activity of the DAO contained in the blood, since the DAO circulates through the body in the blood. The blood is mixed with a substance similar to histamine and the degradation of this substance is measured. The larger the quantity of DAO in the blood, the larger is the portion of the substance that is degraded. In the next step - as a basis for therapy - two possible causes of histamine intolerance can be determined by means of further diagnostics. Copper is a central component in the DAO. If not enough copper is present, DAO cannot be produced in sufficient quantities. Vitamin B6 is a co-factor that means that the DAO cannot convert any histamine without this factor. If a reduced DAO activity is found, the determination of vitamin B6 and copper in the serum can be made in a second step.
Sattler J et al. Agents and Actions 23:361- 65 (1988)
Tufvesson G et al. Scand J Cli Lab Invest 24:163-68. (1969)
Wantke F et al. Inflammation Research 48:169-70. (1999)
Wantke F et al. Allergy Proceedings 15:27- 32. (1994)
Wantke F et al. Inflammation Research 47:396-400. (1998)
Jarisch R et al. In: Wüthrich B (Hrsg): The Atopy Syndrome in the Third Millenium. Curr Probl Dermatol, Basel, Karger, 28:64- 73. (1999)
Wantke F et al.) Clin Exp Allergy 23: 982- 85. (1993)
Götz M et al. Allergologie 9: 426-30. (1996)
Jarisch R Stuttgart, Thieme 21 (1999)
The Laboratory holds all certificates, accreditations and licences issued by the Canadian and Quebec Government Health Services and all procedures respect the highest standards of quality and security.Read more...