What is DAO Deficiency?

DAO Deficiency is an alteration in the metabolism of food histamine that occurs when the activity of the Diamine Oxidase (DAO) enzyme is reduced. That is, when for certain reasons (genetic alterations, illnesses, or the consumption of certain drugs) a considerable deficiency is created in the functional activity of the main histamine metabolization enzyme.
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Histamine and DAO Deficiency

Histamine is a vital molecule derived from the amino acid histidine. It is involved in numerous physiological functions such as maintaining the balance between sleep and wakefulness,
regulating the secretion of gastric juice, responses in allergic processes or as a neurotransmitter in the central nervous system.

One of the implications of this substance, and perhaps the best known, is that it acts against allergic reactions. In this case we are talking about endogenous histamine, produced by the body itself as a defense mechanism. Once the reaction is finished, the levels of this molecule are restored.

Another way in which histamine accumulates in the body is through what we call exogenous histamine. It comes from ingested food and must be metabolized by the enzyme DAO in
the intestine to prevent it from passing through the intestinal epithelium into the bloodstream, generating this accumulation.

Exogenous histamine has no physiological function, so its accumulation in the plasma causes a disproportion to endogenous histamine, which leads to the appearance of adverse effects.

Adverse effects of DAO Deficiency

The increase in circulating histamine is caused by an unrelated accumulation of exogenous histamine consumed through the diet, together with the low activity of the enzyme DAO to degrade it.

Unlike food allergy, the onset of symptoms is not linked to the consumption of a specific food but can be associated with a wide range of foods with variable histamine levels.

This makes it difficult to establish a maximum tolerable dose. In fact, there is still no clear consensus on this value, but normal values of histamine in blood (50-70 mg/l) are established as normal values.

Origin of DAO Deficiency

The 3 identify origins of DAO Deficiency are (1):

• Genetic: The most common cause. Polymorphism in 4 variants of the DAO enzyme gene (AOC1).

• Pathological: DAO deficiency may be caused by an intestinal mucosal damage derived from certain inflammatory bowel pathologies.

• Pharmacological: DAO deficiency may be due to the inhibitory effect of some drugs. It is a temporary and reversible DAO Deficiency.

(1) International Society of DAO Deficiency.

The wide variety of symptoms derived from DAO Deficiency, that represent chronic pathologies of great prevalence in the population, demands the nonstop research in this field: that progress must be increasingly fast.

15% of the population suffers from DAO Deficiency, being more prevalent in women than in men.

The symptom picture of DAO Deficiency includes:

• Migraine and headache, and associated symptoms such as nausea and vomiting.

• Dermatological disorders such as dry skin, atopy or psoriasis.

Migraine

87%

Atopic skin

19 - 57%

Fibromyalgia

78%

ADHD

78%

Food intolerance

80%

Gastrointestinal disorders

67%

1. Izquierdo-Casas, J., Comas-Basté, O., Latorre-Moratalla, M.L. et al. Low serum diamine oxidase (DAO) activity levels in patients with migraine. J Physiol Biochem. 2018. https://doi.org/10.1007/s13105-017-0571-3 
2. Maintz, L., Benfadal, S., Allam, J.P., Hagemann, T., et al. Evidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema. J Allergy Clin Immunol. 2006. https://doi.org/10.1016/j.jaci.2005.11.041 
3. Okutan, G., Ruiz Casares, E., Perucho Alcalde, T., et al. Prevalence of Genetic Diamine Oxidase (DAO) Deficiency in Female Patients with Fibromyalgia in Spain. Biomedicines. 2023. https://doi.org/10.3390/biomedicines11030660 
4. Blasco-Fontecilla, H. Is Histamine, and Not Acetyl-choline, the Missing Link between ADHD and Allergy? The Speer Allergic Tension Fatigue Syndrome Re-visited. Preprints.org.  2023. https://doi.org/10.20944/preprints202305.2186.v1
5. Schnedl, W.J., Lackner, S., Enko, D., et al. Evaluation of symptoms and symptom combinations in histamine intolerance. Intest Res. 2019. https://doi.org/10.5217/ir.2018.00152

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