Diamine oxidase

Synonym(s): DAO, histaminase

Nutrient group: Enzymes

Sources and physiological effects

Dietary sources
The enzyme diamine oxidase (DAO), also called histaminase, is produced by mammals in hepatocytes and is found in the intestines, liver and kidneys. It does not occur in food, as it is destroyed by heat during cooking of the offal.
Physiological effects
Histamine degradation	Catalyzes the degradation of histamine

Detailed information

Histamine intolerance

Histamine is a biogenic amine. In the human body, histamine performs a number of functions as a tissue hormone, neurotransmitter, messenger and inflammatory mediator for allergic and pseudoallergic reactions. Histamine is produced by mast cells, basophilic granulocytes and some neurons and is stored intracellularly in vesicles and released during stimulation.
Histamine, its precursor histidine and other biogenic amines are present in almost all foods in varying concentrations. Products that have matured, been stored or fermented for long time periods are particularly rich in histamine. This is because histamine is produced bacteria via the decarboxylation of the semi-essential amino acid histidine during maturation and fermentation processes.
Histamine intolerance (histaminosis, HIT) is an intolerance to histamine found in food. This intolerance is caused by a lack of histamine-degrading diamine oxidase (DAO) or by a mismatch between histamine supply and degradation (1).
If DAO activity is reduced, even small amounts of histamine can cause strong reactions, which can manifest themselves through the distribution of histamine receptors in multiple organs. The typical symptoms range from gastrointestinal complaints, histamine headache, quincke edema (swelling of the lips), hypertension, arrhythmia, flush, urticaria, congested nose, reddened eyes, dysmenorrhea to anaphylaxis (2).

Histamine degradation by the enzyme diamine oxidase

While intracellular histamine is degraded by the enzyme histamine-N-methyltransferase (HNMT), histamine absorbed through food or produced in the intestinal flora is inactivated (3) by the diaminooxidase (DAO) formed in the intestinal mucosa. Diamine oxidase is continuously produced and secreted into the intestinal lumen. In healthy people, the histamine found in food is broken down in the intestines. In people with histamine intolerance, the degradation rate is reduced by the lack of diamine oxidase activity. Increased exogenous histamine exposure can lead to overloading of the inactivation system, resulting in allergy-like complaints (2). Causes for reduced DAO activity can be intestinal diseases such as a colon adenoma (4), a congenital or a transient DAO deficiency due to inflammation of the intestinal mucosa (5) or a lack of micronutrients which are essential for the development or activity of DAO (1). In addition to reduced DAO activity, other biogenic amines and drugs can also inhibit histamine degradation by DAO. In addition to drugs, the role of alcohol should not be underestimated, as some alcoholic beverages themselves contain histamine and ethyl alcohol can reduce DAO activity and lead to the release of histamine from mast cells and basophils (6).

Reference values

Substrate	Parameter	Reference value	Description
Serum	DAO	> 4.5 U/ml	In the classical constellation of HIT the histamine level is increased, while the DAO activity is reduced with reduced vitamin B₆.
2nd morning urine	Histamine	10-50 µg/g Creatinine	If a strongly elevated histamine level is present, then despite normal or slightly elevated DAO activity histamine intolerance can be diagnosed (example: anaphylaxis – strongly increased histamine concentration, DAO activity not sufficient).
12-hour collection	Histamine	5-25 µg
Interpretation
High histamine values		Insufficient activity of diamine oxidase. Increased intestinal formation of biogenic amines (e.g. cadaverine, putrescine and histamine) in decay dysbiosis (in stool) Increased degranulation of intestinal mast cells in the context of type I allergies to food
Note on the interpretation of results
A detailed patient history is essential for the diagnosis of histamine intolerance, which investigates nutritional habits and documents the temporal relationship between food intake and complaints.

Deficiency symptoms

Impact on	Symptoms
General well-being	Histamine headache, dysmenorrhea
Cardiovascular	Quincke edema (swelling of the lips), hypertension, arrhythmia, congested nose, reddened eyes, anaphylaxis
Gastrointestinal tract	Gastrointestinal complaints
Skin	Flush, urticaria

Indications

Effect

Indication

Dosage

Physiological effects
at a low intake

Food intolerances due to histamine intolerance

as treatment: 1,5 mg/d

after that: 0,8 - 1 mg/d

Administration

General mode of administration
When	Diamine oxidase should be taken immediately before a histamine-rich meal. It is recommended to start with a course of treatment spread over the day (1,5 mg daily over a month). After that the supplement should be taken immediately before the intake of histamine-rich meals (0,8 - 1 mg/d).
Side effects
No relevant side effects known to date.
Contraindications
No relevant contraindications known to date.

Interactions

Drug interactions
None	No relevant interactions are known to date.
Nutrient interactions
Vitamins	Vitamin B₆ as coenzyme of DAO and concomitant intake may show an improvement in symptoms.

References

1) Martin, M. 2006. Allergiediagnostik. In Martin M (Hrsg): Labormedizin in der Naturheilkunde.

2) Maintz, L. 2006. Die verschiedenen Gesichter der Histaminintoleranz. Konsequenzen für die Praxis. Deutsches Ärzteblatt. 51-51(103):3477-83.

3) Maintz, L., Novak, N. 2007. Histamine and histamine intolerance. Am J Clin Nutr. 85(5):1185-96.

4) Kuefner, M. A. et al. 2008. Decreased histamine catabolism in the colonic mucosa of patients with colonic adenoma. Dig Dis Sci. 53(2):436-42.

5) Raithel, M. et al. 1995. Mucosal histamine content and histamine secretion in Crohn's disease,ulcerative colitis and allergic enteropathy. Int Arch Allergy Immunol. 108(2):127-33

6) Wüthrich, B. 2009.Histamininotleranz: Fakt oder Fiktion? TMJ (2).

References Interactions:
Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.

Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.

Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.