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DAO deficiency

Is an alteration in the metabolism of food histamine that appears when the Diamine Oxidase (DAO) enzyme activity is low, in other words, when for some causes (genetic disorders, diseases and consumption of certain drugs) there is a significant deficiency in the functional activity of the main enzyme in the metabolism of histamine.

In healthy people, histamine from the diet is degraded by the enzyme diamine oxidase (DAO), however, in people with low activity of this enzyme is has the risk of an accumulation of plasmatic histamine, referenced until recently as “Histamine intolerance”. This term is a concept that today we consider simplistic once demonstrated the extent of the DAO deficiency and its greater prevalence in the population, since increased circulating histamine does not actually occurs by an intolerance but by an silent accumulation, without temporal relationship between food intake of histaminic foods and the onset of symptoms.

The imbalance between ingested histamine and the histamine released from the histamine storage cells, and the capacity for histamine degradation, leads to histamine accumulation in plasma and the occurrence of adverse effects on health.

Differentiation of adverse effects

Unlike food allergy, the occurrence of symptoms or adverse effects is not linked to the intake of specific food; not only can it be related to a wide variety of food with different histamine contents, symptoms can also occur even after the ingestion of products with low histamine levels. This imposed considerable difficulty when establishing a maximum tolerable dose; in fact, there is no clear consensus on this value.

Values that range from 50μg of histamine (in one serving of wine, 125ml, for example) to 60-75mg, prior pure histamine administration, have been listed as triggers of DAO Deficiency symptoms.

Due to the wide variety of symptoms derived from DAO Deficiency, which represent chronic pathologies with a high prevalence in population, immediate research and advances on its origin and possible treatments are required.

Most frequent symptoms derived from DAO Deficiency 

It is not necessary for all symptoms to manifest, although most patients with low functional DAO activity present an average of three of those symptoms, being migraine the prevalent one.

20% of patients experience 1 or 2 of these associated symptoms, 41.3% of patients experience 3 or 4 of these symptoms and 33.8% present more than 5.

The most frequent symptoms derived from DAO Deficiency are:

• Migraine and other vascular headaches.
• Gastrointestinal disorders, especially those associated with irritable bowel syndrome, such as constipation, diarrhea, satiety, flatulence or swollen feeling.
  
• Dermatological disorders such as dry skin, atopy or psoriasis.
• Soft-tissue pains usually diagnosed asfibromyalgia.
• Chronic fatigue.
• In childhood and adolescence, DAO deficiency has been linked to Attention Deficit and Hyperactivity Disorder (ADHD).
• Bronchial asthma, wheezing, respiratory disorders.

Route of histamine in the body

In the metabolism of histamine, when it should be degraded by DAO enzyme in order to become N-acetyl aldehyde imidazole, an accumulation of the amine is produced due to the deficiency in the activity of the enzyme in the intestinal mucosa cells. Low enzyme activity causes that a concentration of histamine which comes from food and is generally considered normal couldn`t be metabolized and triggers a transepithelial permeation of exogenous histamine.

By this way histamine enters the bloodstream, increasing its plasma concentration, and once located free in blood it spreads throughout the body.