Histamine Degradation – Enzymes, Function and Disorders
Histamine degradation refers to the enzymatic processes by which the body breaks down and neutralises histamine. Impaired degradation can lead to histamine intolerance and related symptoms.
Things worth knowing about "Histamine Degradation"
Histamine degradation refers to the enzymatic processes by which the body breaks down and neutralises histamine. Impaired degradation can lead to histamine intolerance and related symptoms.
What Is Histamine Degradation?
Histamine degradation describes the biochemical processes through which the human body enzymatically breaks down and eliminates histamine – a biogenic amine. Histamine is produced both within the body (endogenously) and absorbed through certain foods (exogenously). It plays a key role in immune responses, gastric acid secretion, and various neurological functions. Efficient histamine degradation is essential to prevent excessive histamine levels in the bloodstream.
Key Enzymes Involved in Histamine Degradation
Two primary enzymes are responsible for breaking down histamine in the human body:
- Diamine Oxidase (DAO): This enzyme is mainly produced in the small intestine, kidneys, and placenta. It degrades exogenous histamine – histamine absorbed from food – in the gut before it enters the bloodstream. A deficiency in DAO activity is considered the most common cause of histamine intolerance.
- Histamine N-Methyltransferase (HNMT): This enzyme acts primarily intracellularly and breaks down histamine within tissues, especially in the central nervous system, liver, and kidneys. It methylates histamine to form N-methylhistamine, which is then further metabolised and excreted via the urine.
The Process of Histamine Degradation
The DAO pathway involves oxidative deamination: histamine is converted to imidazoleacetaldehyde, which is further oxidised to imidazoleacetic acid and excreted through the kidneys. The HNMT pathway transfers a methyl group to histamine, producing N-methylhistamine, which is subsequently broken down by monoamine oxidase B (MAO-B) into N-methylimidazoleacetaldehyde and ultimately into N-methylimidazoleacetic acid.
Disorders of Histamine Degradation
When the body's degradation capacity is exceeded by the amount of histamine ingested or produced, symptoms can arise. Common causes of impaired histamine degradation include:
- Genetically determined DAO deficiency (reduced enzyme activity)
- Inflammatory bowel diseases (e.g. Crohn's disease, ulcerative colitis) that inhibit DAO production
- Use of DAO-inhibiting medications (e.g. certain antibiotics, antihistamines, pain relievers)
- Alcohol consumption, which both inhibits DAO activity and itself contains histamine
- Dietary overload from histamine-rich foods (e.g. red wine, aged cheese, canned fish)
Histamine Intolerance and Histamine Degradation
Histamine intolerance is primarily caused by a reduced capacity to degrade histamine, most often due to diminished DAO activity. Typical symptoms include headaches, skin flushing, itching, gastrointestinal complaints, palpitations, and nasal congestion. Diagnosis is based on medical history, a food diary, DAO activity measurement in blood, and an elimination trial with a low-histamine diet.
Treatment of Impaired Histamine Degradation
Treatment is tailored to the underlying cause and may include:
- Low-histamine diet: Avoiding foods high in histamine and histamine liberators
- DAO supplementation: Taking DAO enzyme supplements before histamine-rich meals to support breakdown
- Antihistamines: Blocking histamine receptors to relieve symptoms
- Treatment of underlying conditions: For example, managing intestinal disease that impairs DAO production
- Avoidance of inhibiting substances: Reducing or eliminating alcohol and DAO-inhibiting medications in consultation with a physician
References
- Maintz L, Novak N. Histamine and histamine intolerance. American Journal of Clinical Nutrition. 2007;85(5):1185-1196. doi:10.1093/ajcn/85.5.1185
- Reese I, et al. Guideline on histamine intolerance. Allergo Journal International. 2017;26(2):72-79.
- Schwelberger HG. Diamine oxidase (DAO) enzyme and gene. Journal of Neural Transmission Supplementa. 2007;(71):3-10.
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