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Histamine Metabolism – Formation, Breakdown and Disorders

Histamine metabolism refers to the production, storage, release, and breakdown of histamine in the human body. Disruptions can lead to intolerances and allergic reactions.

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Things worth knowing about "Histamine Metabolism"

Histamine metabolism refers to the production, storage, release, and breakdown of histamine in the human body. Disruptions can lead to intolerances and allergic reactions.

What is Histamine Metabolism?

Histamine metabolism encompasses all biochemical processes involved in the formation, storage, release, and degradation of histamine in the human body. Histamine is a biogenic amine that plays a central role in immune responses, gastric acid secretion, sleep-wake regulation, and neurotransmission.

A well-functioning histamine metabolism ensures that excess histamine is efficiently broken down and that the body does not overreact to normal histamine levels. When this balance is disrupted, a wide range of symptoms can occur.

Formation and Sources of Histamine

Histamine is primarily produced in the body through the decarboxylation of the amino acid L-histidine, catalyzed by the enzyme histidine decarboxylase (HDC). It is produced and stored in:

Mast cells and basophils (within the immune system)
Enterochromaffin-like cells of the gastric mucosa
Neurons in the central nervous system

In addition, histamine is ingested through food. Foods particularly high in histamine include fermented products such as aged cheese, red wine, sauerkraut, salami, fish, and legumes.

Breakdown of Histamine

Histamine is broken down through two major enzymatic pathways:

Diamine Oxidase (DAO)

Diamine oxidase (DAO) is the primary enzyme responsible for degrading dietary histamine. It is mainly active in the mucosa of the small intestine, kidneys, and placenta. A deficiency in DAO activity is a leading cause of histamine intolerance.

Histamine N-Methyltransferase (HNMT)

Histamine N-methyltransferase (HNMT) degrades histamine intracellularly, primarily in the central nervous system and liver. It transfers a methyl group onto histamine, rendering it biologically inactive.

Regulation and Histamine Receptors

Histamine exerts its effects through four known receptor subtypes:

H1 receptors: Involved in allergic reactions, inflammation, itching, and bronchospasm
H2 receptors: Stimulate gastric acid production
H3 receptors: Regulate neurotransmitter release in the brain
H4 receptors: Involved in immunological processes and inflammatory responses

Disorders of Histamine Metabolism

Disruptions in histamine metabolism can cause various conditions and complaints:

Histamine intolerance: Caused by a relative excess of histamine, most often due to reduced DAO activity. Symptoms include headaches, skin reactions, gastrointestinal discomfort, palpitations, and dizziness.
Mastocytosis: A condition characterized by an abnormal accumulation of mast cells, leading to excessive histamine release.
Allergic conditions: In immediate-type (type I) allergic reactions, histamine is rapidly and massively released from mast cells.

Factors Affecting Histamine Metabolism

Several factors can influence histamine metabolism:

Certain medications (e.g., antihistamines, non-steroidal anti-inflammatory drugs, antidepressants) can inhibit histamine degradation
Alcohol inhibits DAO activity while simultaneously promoting histamine release
Vitamin B6, vitamin C, and copper are important cofactors for DAO activity
Gastrointestinal disorders (e.g., Crohn's disease, celiac disease) can reduce DAO production
Hormonal influences, particularly estrogen, can amplify histamine release

Diagnosis and Treatment

Several diagnostic approaches are available for evaluating histamine metabolism disorders:

Measurement of DAO activity in the blood
Determination of histamine levels in plasma or urine
Provocation tests and elimination diets

Treatment depends on the underlying cause and may include a low-histamine diet, DAO supplementation, the use of antihistamines (H1 and H2 blockers), and avoidance of histamine-liberating substances.

References

Maintz L, Novak N. Histamine and histamine intolerance. American Journal of Clinical Nutrition. 2007;85(5):1185-1196.
Schink M et al. Microbial patterns in patients with histamine intolerance. Journal of Physiology and Pharmacology. 2018;69(4).
World Allergy Organization (WAO). Histamine Intolerance - Position Paper. 2020. Available at: www.worldallergy.org

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