histamine N-methyltransferase (HNMT)
The second major enzyme responsible for breaking down histamine. Unlike DAO, it works inside cells within the brain, lungs, skin, and liver. It cannot be supplemented in capsule form.
While DAO breaks down histamine outside of cells (mainly the histamine we ingest through food), HNMT handles histamine inside cells. Both pathways complement each other, with each responsible for a different territory: DAO covers the intestines, kidneys, and placenta, while HNMT covers the central nervous system, bronchi, skin, and liver. Histamine in the brain can only be broken down by HNMT, as DAO cannot enter nervous tissue.
During the reaction, HNMT attaches a methyl group to histamine (with S-adenosylmethionine serving as the donor), forming N-methylhistamine, which is further broken down and excreted in the urine. This is precisely why urinary N-methylhistamine is used as a laboratory marker for histamine turnover in the body.
HNMT activity is influenced by genetic variants. The most well-known is the C314T (Thr105Ile) polymorphism, which slows the enzyme down. Carriers of this variant can experience issues even with normal DAO levels. Unlike DAO, HNMT cannot be taken as a dietary supplement. Therefore, for reduced HNMT activity, enzyme replacement won't help; instead, a consistent reduction of the overall histamine load is required.
Related terms
Substances that reduce the activity of the DAO enzyme, which worsens the breakdown of histamine.
An enzyme that breaks down biogenic amines, such as tyramine or serotonin. It also completes the degradation of histamine after it has been processed by HNMT.
DAO enzyme supplementation for better histamine breakdown in histamine intolerance.
DAO enzyme supplementation for better breakdown of dietary histamine in people with HIT.
Substances that the DAO enzyme needs to do its job, mainly copper and vitamin B6. Without them, the enzyme cannot work at full capacity, even if there is enough of it in the body.