Wissenswertes

Histamine N-methyltransferase (HNMT) degradation disorder

Histamine N-methyltransferase , or HNMT for short, is a naturally occurring enzyme in the body. Why is this enzyme so important in connection with histamine intolerance? A deficiency in HNMT breakdown means that histamine cannot be properly broken down. This blog article explains the processes that occur in your body when this breakdown is impaired and offers helpful tips.

How does histamine intolerance manifest itself?

There is no single set of symptoms associated with histamine intolerance, as the symptoms vary from person to person and differ in severity . This is because histamine intolerance affects almost all organs. The following symptoms may occur:

Typical and cutaneous symptoms: skin redness, itching, flushing, hives
Respiratory: blocked nose, asthma attacks, runny nose
Gastroenterological: Diarrhea and constipation, flatulence, abdominal pain
cardiac: heart rhythm disorders, low blood pressure, high blood pressure
Headaches and menstrual cramps
Dizziness, nausea and vomiting

The enzymes diamine oxidase (DAO) and histamine N-methyltransferase are required for histamine breakdown; both are produced in most cells. However, the amounts produced vary considerably depending on the cell type or organ.

DAO deficiency and symptoms

The enzyme DAO is considered one of the most important histamine breakdown pathways in the human body. It primarily acts in the intestines , breaking down extracellular histamine , especially from food, within the chyme. The enzyme is not particularly well protected from external chemical influences, as it is secreted from the cell interior into the intestines, where it is no longer protected from the substances present there. A deficiency of DAO leads to an excess of histamine and thus to histamine-related symptoms .

The woman is exhausted

HNMT degradation disorder and symptoms

Besides DAO, the enzyme HNMT is responsible for the breakdown of intracellular histamine in the body, particularly in the detoxification organs liver and kidneys , but also in the central nervous system (CNS), skin, and bronchial mucosa. Therefore, impaired HNMT breakdown is also called cellular histaminosis .

HNMT is therefore considered an equally important factor in histamine breakdown. However, if the HNMT enzyme is impaired in its function and histamine cannot be adequately broken down, histamine intolerance and its symptoms can worsen . An increased risk of developing secondary diseases has also been demonstrated. While HNMT is better protected from external chemical influences within the cell, foreign substances still affect its synthesis. Causes of impaired function can include:

Temporary or acquired reduction in activity due to external factors such as medications (HNMT blockers), an overloaded liver, nutrient deficiencies, or chemical environmental influences such as heavy metal exposure.
genetically determined, i.e. permanent, deficiency of HNMT or persistent functional impairment

INFO: Reduced HNMT activity usually occurs because various factors combine. Many affected individuals also have problems with histamine breakdown in the gut.

The effect of HNMT compared to DAO

The organs where HNMT is active have a particularly high number of mast cells . If symptoms manifest especially in the liver, kidneys, brain, and skin, a mast cell disorder , such as a mast cell activation disorder like mast cell activation syndrome (MCAS), may also be present.

Mast cell disorders can also lead to insufficient HNMT activity in these areas. Histamine breakdown in the central nervous system, i.e., in the brain, functions exclusively via HNMT, not via DAO. It is therefore not surprising that neurological symptoms are prominent in cases of impaired HNMT breakdown.

As mentioned previously, HNMT dysfunction has no significant impact on the breakdown of histamine from food, unless it involves histamine liberators. Histamine liberators trigger the release of the body's own histamine. This can occur through the consumption of certain foods or through stress and physical exertion . It is reasonable to assume that HNMT dysfunction leads to a chronically slightly elevated histamine level, especially when mast cells release large amounts of histamine.

In such a case, the histamine level would rise higher and remain at that level for a longer period, unlike in a normally functioning HNMT. Given these explanations, it is not surprising that some people with chronic histamine intolerance experience symptoms only after hours or even days of consuming histamine-rich foods, and these symptoms often only subside completely days later. In contrast, with a DAO degradation disorder, acute symptoms appear within minutes of consuming histamine-rich foods and usually subside quickly.

However, things can become even more complicated if histamine metabolism is disrupted . If the histamine level in the body is very high, large amounts of histamine breakdown products are formed during histamine breakdown by HNMT. These, in turn , inhibit HNMT activity , causing the body's entire histamine breakdown capacity to temporarily cease before eventually normalizing. Such a breakdown blockage with intense symptoms over a prolonged period occurs primarily when a low-histamine diet is not consistently followed. Cyclical flare-ups are also not uncommon in the initial phase of a mast cell disorder, such as mastocytosis.

Diagnostic options for HNMT degradation disorder

To determine the functionality of the DAO enzyme, both DAO activity in blood serum and plasma histamine levels are measured during diagnostics. To detect HNMT degradation, however, the methylhistamine concentration in urine is evaluated. It should be noted, however, that methylhistamine levels also rise after consuming protein-rich foods.

Can HNMT degradation be counteracted?

Are there HNMT tablets to counteract a histamine breakdown disorder ? There are indeed antihistamines containing the active ingredient dimetindene, which are supposed to stimulate HNMT and promote histamine breakdown. However, these do not address the underlying cause of the problem. Other measures that can be taken include the following:

Avoid HNMT blockers : These include certain active ingredients in medications, such as diphenhydramine. Certain dietary supplements and recreational substances are also suspected of blocking HNMT. Since there is no scientific evidence to support this, it must be determined individually whether abstaining from these substances provides relief.
Elimination diet : strict avoidance of histamine, histamine liberators, and enzyme blockers.
Drug therapy in the presence of a mast cell disorder
Consume nutrients that promote HNMT production.
Relieve and strengthen the liver

Of particular interest is a study of HNMT inhibitors , which found that they block histamine breakdown . This includes, among others, diphenhydramine, an H1 antihistamine. Furthermore, the same effect was observed with...

Tacrine (Alzheimer's medication)
Amodiaquine (malaria drug)
and metoprine fixed.

What they all have in common is that they block the histamine binding site of the enzyme , thus preventing histamine from reaching the active HNMT center.