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Histamine-Degrading Enzyme – Function, Deficiency and Treatment

A histamine-degrading enzyme breaks down histamine in the body. A deficiency of these enzymes can lead to histamine intolerance and a range of uncomfortable symptoms.

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Things worth knowing about "Histamine-Degrading Enzyme"

A histamine-degrading enzyme breaks down histamine in the body. A deficiency of these enzymes can lead to histamine intolerance and a range of uncomfortable symptoms.

What Is a Histamine-Degrading Enzyme?

A histamine-degrading enzyme is an enzyme in the human body responsible for breaking down and neutralising histamine – a biogenic amine that acts as a chemical messenger in immune responses, gastric acid production, and sleep regulation. When histamine is not broken down efficiently, it can accumulate in the body and trigger a range of symptoms.

The two most important histamine-degrading enzymes are diamine oxidase (DAO) and histamine N-methyltransferase (HNMT). DAO is primarily active in the gut, where it degrades dietary histamine, while HNMT acts mainly intracellularly – inside the cells – throughout various tissues.

Mechanism of Action

Diamine oxidase (DAO) is a copper-dependent enzyme produced in the enterocytes (intestinal cells). It oxidises histamine through an enzymatic reaction, converting it into imidazoleacetaldehyde, which is further broken down into harmless metabolites. DAO requires specific cofactors to function properly, including vitamin B6, vitamin C, and copper.

Histamine N-methyltransferase (HNMT) methylates histamine using S-adenosylmethionine (SAM), converting it into N-methylhistamine, which is biologically inactive. This enzyme is particularly active in the liver, kidneys, and bronchial mucosa.

Causes of Histamine-Degrading Enzyme Deficiency

A deficiency or reduced activity of histamine-degrading enzymes, particularly DAO, is the most common cause of histamine intolerance. Possible causes include:

Genetically reduced DAO production
Intestinal disorders (e.g., Crohn's disease, coeliac disease, irritable bowel syndrome)
Certain medications that inhibit DAO activity (e.g., some antihistamines, antibiotics, antidepressants)
Nutritional deficiencies in cofactors such as vitamin B6, vitamin C, and copper
Alcohol consumption, which inhibits DAO activity
Excessive intake of histamine-rich foods

Symptoms of Deficiency

When histamine-degrading enzymes are insufficiently active, excess histamine can accumulate and cause a wide range of complaints. Common symptoms include:

Headaches and migraines
Skin reactions such as flushing, itching, or hives (urticaria)
Gastrointestinal complaints (bloating, diarrhoea, abdominal cramps)
Runny or blocked nose (rhinitis)
Heart palpitations (tachycardia)
Sleep disturbances and fatigue
Dizziness and blood pressure fluctuations

Diagnosis

The diagnosis of a histamine-degrading enzyme deficiency is typically based on a combination of medical history, symptom assessment, and laboratory testing. DAO activity in the blood serum can be measured directly. Additional tests may include histamine levels in blood or urine, as well as an elimination diet to assess tolerance to histamine-rich foods.

Treatment and Management

Treatment for histamine-degrading enzyme deficiency involves several approaches:

Low-histamine diet: Avoiding foods high in histamine such as aged cheese, red wine, salami, sauerkraut, and smoked fish
DAO supplementation: Taking dietary supplements containing diamine oxidase to support the body's own DAO activity
Cofactor supplementation: Ensuring adequate intake of vitamin B6, vitamin C, and copper, which support enzyme function
Antihistamines: In acute situations, H1 or H2 antihistamines may be used to block the effects of excess histamine
Treatment of underlying conditions: When DAO deficiency is secondary to an intestinal disorder, addressing the root cause is essential

References

Maintz L, Novak N. Histamine and histamine intolerance. American Journal of Clinical Nutrition. 2007;85(5):1185-1196.
Schwelberger HG. Diamine oxidase (DAO) enzyme and gene. In: Falus A (ed.). Histamine: Biology and Medical Aspects. SpringMed Publishing, Budapest, 2004.
World Health Organization (WHO). Food safety and foodborne illness. WHO Fact Sheets. Geneva, 2022. Available at: https://www.who.int

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