Test of diamine oxidase (DAO) level

For various reasons, most often the consumption of foods rich in this substance or in the case of a deficiency of the enzyme that breaks it down, it accumulates in the bloodstream and causes various intestinal and extraintestinal problems. The resulting condition often resembles a classic food allergy. The essence of the blood serum examination is the determination of the level of the enzyme diamine oxidase (DAO), whose role is to break down histamine received in food. (1)

Why take a serological test for histamine intolerance

1. Serological examination of histamine intolerance effectively differentiates patients with a high probability of histamine intolerance from healthy patients. (2)
2. The examination is recommended as an additional examination to rule out the causes of digestive problems. It is a clarifying, but not basic examination with clarifying informative value. Serum DAO determination has limited ability to discriminate between patients with high and low probability of histamine intolerance, according to expert research. However, it is not enough to confirm or refute the diagnosis of HIT. (2)
3. Severity of HIT symptoms was greater in patients with low or moderate DAO levels compared to those with higher DAO levels, according to a 2022 study, making HIT a more difficult to diagnose problem that needs to be picked up by all available methods. (3)
4. The results of the blood test, which tests the level of the diamine oxidase enzyme, are available within 10 working days.

When is it appropriate to undergo a serological test for histamine intolerance

The diagnosis of histamine intolerance remains difficult. Experts in clinical diagnosis encounter an obstacle in the form of possible confusion of HIT with other similar conditions, for example with food intolerances, with irritable bowel syndrome or with non-celiac gluten sensitivity. (2) Symptoms of HIT include both intestinal and extraintestinal manifestations.

Gastrointestinal symptoms most often include:

• bloating,
• abdominal pain,
• flatulence,
• diarrhea or constipation,
• nausea and/or vomiting.

Extraintestinal symptoms, which can occur anywhere because histamine receptors are located throughout the body, include:

• nausea, headache, palpitations, skin manifestations including itching, redness, urticaria, dermatitis and swelling,
• respiratory symptoms, e.g. runny nose, stuffy nose, shortness of breath and sneezing,
• disorders of the menstrual cycle. (10)

Many scientific studies confirm that gastrointestinal manifestations are the most common in HIT, with bloating occurring in 92% of subjects in an Austrian study of 133 patients. Other symptoms included constipation (55%), abdominal pain (68%), diarrhea (71%) and feeling full after eating (73%). In terms of skin manifestations, the most common symptom was itching (48%), in terms of other organs, the most frequently reported symptoms were dizziness (66%), headache (65%) and palpitations (47%). (10) If you notice any of these symptoms in yourself, you can undergo a serological test to help detect HIT, which is one of the possible causes of these symptoms.

What you should know about histamine intolerance before you undergo an examination

The mentioned Austrian research from 2019 confirms that due to the wide spectrum of manifestations and symptoms affecting a number of organs and due to the relative lack of information on in vitro and in vivo diagnostic tests for HIT, the detection of histamine intolerance is still relatively difficult. (2) (10) At present, histamine intolerance is determined primarily clinically, with two aspects being followed:

1. whether there will be an improvement in symptoms after starting a diet with a low content of biogenic amines,
2. whether treatment with antihistamines will work.

Measurement of serum DAO enzyme concentration and activity is still the most widely used laboratory diagnostic test for HIT. Despite the fact that there are some doubts about whether it is suitable for diagnosing the disease, it is an irreplaceable additional examination. (2) In order to determine the diagnosis of HIT, other causes of symptoms must first be ruled out using:

• skin allergy test (e.g. skin prick test) to rule out food allergy,
• determination of tryptase enzyme in plasma to rule out systemic mastocytosis,
• medication anamnesis to determine whether you are taking medications affecting DAO. (6)

The following are suggested as additional tests:

• histamine skin test (the doctor injects a small amount of histamine under your skin, and when the area turns red within 50 minutes, your body has problems breaking it down),
• intestinal biopsy,
• measurement of histamine in urine. (5)

However, the data on the usefulness of these diagnostic tests are still not satisfactory. (6) Due to problems with recognition, the prevalence of HIT is strongly underestimated and, according to experts, ranges between 1 and 3%. (2)

The most effective measure for suspected histamine intolerance is to follow a diet with a low content of biogenic amines, which contributes not only to the relief of symptoms, but also to the improvement of DAO enzyme activity. (2)

What´s measured

About histamine

Histamine is a biogenic amine that is produced by synthesis from the amino acid histidine and is involved in many physiological processes. Histamine produced by the body itself (so-called endogenous histamine) is stored mainly in mast cells and basophilic leukocytes (a type of white blood cell) and is one of the main mediators of clinical reactions mediated by IgE antibodies.

Endogenous (i.e. produced in the body) and exogenous (i.e. obtained from food) histamine is broken down by two degradation pathways:

1. methylation by histamine-N-methyltransferase (HNMT),
2. by oxidative degradation by diamine oxidase (DAO).

Histamine in food can be a trigger for health problems. However, no pathophysiological mechanism, such as a deficiency of one of the enzymes that degrade histamine (eg, diamine oxidases or histamine-N-methyltransferases), has been demonstrated in prospective, controlled studies. (7) Although many conflicting opinions are described in the literature, recent studies repeatedly declare the importance of measuring DAO in serum or using it to identify affected individuals with histamine intolerance. (7)

Histamine intolerance is caused by reduced intestinal inactivation and degradation of histamine. The main enzyme responsible for the degradation of exogenous histamine is DAO, released primarily in the epithelial cells of the small intestine, placenta, kidneys and liver. (7) (8) Under normal conditions, it is represented in the bloodstream in low concentrations and participates not only in the degradation of histamine, but also of other biogenic amines.

Diseases that can damage the intestinal mucosa, including lactose intolerance and celiac disease, they can also disrupt DAO activity. Inflammation causes damage to the intestinal mucosa, which leads to a decrease in the expression and activity of DAO and to the possible development of the so-called secondary HIT. The severity of damage to the intestinal epithelium correlates with the degree of reduction in DAO activity. (2) Secondary HIT can also be induced by drugs that interfere with DAO activity, such as antibiotics, antimalarials, antituberculosis drugs, H2 receptor antagonists, antihypertensives, analgesics, mucolytics, antidepressants, antiemetics, and muscle relaxants. (1) (5) (9)

Symptoms of histamine intolerance usually appear two hours to one day after eating foods rich in biogenic amines. (2) The richest in biogenic amines are fermented foods (sauerkraut), chocolate, alcoholic beverages (red wine and champagne), cheeses (maturing), meat (sausages), canned foods (especially fish), vegetables (tomatoes, eggplant and spinach ), fruit (pineapple, grapefruit and kiwi), bread and nuts. (2) (3) (5) The concentration of histamine also depends on the process of food preparation and storage.