Histamine intolerance

Histaminosis or excess histamine in the blood occurs when there is a high intake of histamine in our diet or when it is not metabolized and eliminated correctly.

Histamine is a substance involved in numerous biological and physiological processes. It is synthesized and stored in granules inside certain blood cells that are part of the immune system and is also present in many foods, either naturally or as a result of the action of microorganisms.

At the physiological level, histamine is involved in the stimulation of gastric juice secretion, inflammation, neurotransmission, smooth muscle contraction, among other processes.

When there is a deficit in the DAO enzyme at intestinal level, histamine is not eliminated correctly and is absorbed in the intestine through which when it reaches the blood it can accumulate in different tissues producing symptoms, which are reversible and transitory, similar to an allergic reaction, such as headache, urticaria, diarrhea and constipation.

Histamine needs to be metabolized in the body to prevent its accumulation and adverse effects. To do this, histamine can follow two pathways: by means of the enzyme diamine oxidase (DAO) or by means of histamine-N-methyltransferase (HNMT).

The function of the DAO enzyme can be altered by several factors

  • Genetic variations.
  • Binding of biogenic amines that may be present in certain foods (putrescine, cadaverine, agamatine). They are usually present in fermented foods or foods that are altered by microorganisms.
  • Interaction with alcohol and its metabolites (acetaldehyde).
  • Antibiotics such as clavulanic acid, cholestimate and cefuroxime, the antihypertensives verapamil and dihydralazine, the analgesic metamizole, the antihistaminesThe antidepressant amitriptyline, the muscle relaxant suxamethonium, ascorbic acid (vitamin C) and thiamine (vitamin B1).

The vast majority of studies that have analyzed the relationship between genetics and histamine intolerance have focused mainly on the study of variations in the AOC1 gene, which codes for the production of the enzyme DAO, which is the main pathway for histamine degradation. From these studies it has been shown that individuals who are carriers of variants in AOC1 produce a DAO enzyme with lower activity, which increases the likelihood of accumulating histamine in the body.

The most relevant variants in the AOC1 gene that affect the function of the DAO enzyme in Caucasians are Thr16Met, Ser332Phe, and especially His645Asp. Another well-known variant is G4586T, which is found in the promoter region of the AOC1 gene and has been related to a decrease in its expression.

Knowing the genetic predisposition to histamine intolerance may be helpful in determining the origin of the intolerance. However, it alone does not explain why a person will eventually develop histamine intolerance, so your results cannot be considered a diagnostic test. As previously mentioned, other factors such as the presence of intestinal diseases, alcohol consumption and drugs that inhibit DAO activity are known to play a role and if you have any symptoms you should consult your physician for a proper evaluation.

Number of observed variants

13.5 million variants

Number of variants analyzed in the study

4 variants


Ayuso P., García-Martín E., et al. Genetic variability of human diamine oxidase: occurrence of three nonsynonymous polymorphisms and study of their effect on serum enzyme activity. Pharmacogenet Genomics. 2007 Sep;17(9):687-93.

Comas-Basté O., Sánchez-Pérez S., et al. Histamine Intolerance: The Current State of the Arts. Biomolecules. 2020 Aug 14;10(8):1181.

García-Martín E., Ayuso P., et al. Histamine pharmacogenomics. Pharmacogenomics. 2009 May;10(5):867-83.

García-Martín E., Martínez C.., et al. Diamine oxidase rs10156191 and rs2052129 variants are associated with the risk for migraine. Headache. 2015 Feb;55(2):276-86.

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