About this test
Abdominal pain after eating, reddening of the skin, a feeling of heat, difficulty breathing, sometimes even palpitations are the most common symptoms of a problem with the breakdown of histamine in food, referred to as histamine intolerance (HIT). Histamine is a substance created and permanently present in the body, and it is also part of many foods consumed daily.
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
- Serological examination of histamine intolerance effectively differentiates patients with a high probability of histamine intolerance from healthy patients. (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)
- 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)
- 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:
- whether there will be an improvement in symptoms after starting a diet with a low content of biogenic amines,
- 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:
- methylation by histamine-N-methyltransferase (HNMT),
- 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.
Instructions before collection
We do not recommend entry of patients/clients with clinical signs of disease (temperature, cough, signs of respiratory tract infection, etc.) to undergo this test.
We recommend hand disinfection prior to entry to the clinics/collection points.
It is advised to fast for a minimum of 8 hours by refraining from eating or drinking anything expect water. Faiing to fast before the test may affect result quality. If you are currently on medications, consult your healtcare provider to determine whether you should continue taking them prior to the test.
PREPARATION FOR BLOOD COLLECTION
The recommended time to collect blood is between 7 a.m. and 9 a.m., to obtain comparable results from different blood draws. To assess the numerical test result, so-called reference intervals are used, which are based on morning fasting collections and are used for population comparison. This time interval is also recommended in light of the biological cycles that naturally take place in the body.
GENERAL PRE-SAMPLING INSTRUCTIONS
It is necessary to come to the testing site earlier, so that you can rest in the waiting room for approximately 20 minutes to have a relatively relaxed body and mind.
It is necessary to arrive on an empty stomach for the collection itself, in the case of collections at a later time in the day, at least three hours on an empty stomach. At home, it is desirable to drink a sufficient amount of pure water (at least up to half a liter) - this is important for a successful blood collection. Mineral water, juice, coffee and tea are not recommended.
Herbs included in tea may contain substances affecting the blood count. Coffee and black tea increase gastric acid production and release insulin from the pancreas, thereby affecting glucose metabolism. Since everything in the body is interrelated, they can impact other tests. Another extreme is when your body is running out of fluids. In this case, the number of red blood cells, the level of protein and lipids bound to the protein increase and the level of urea in the blood can also increase. It is therefore advisable to drink pure water when you wake up.
Generally, it is recommended to:
• around 6 p.m. eat only light meals, do not eat fatty food (cheese, butter, cream, meat, smoked meat, bacon) and sweet meals,
• fast for 10-12 hours (Attention: it is not advisable to starve for more than 16 hours!), in the case of later collection (after 9:30 a.m.), a lighter breakfast is allowed, no later than 3 hours before collection,
• drink non-alcoholic beverages and drinks without sugar in the usual quantity, in the case of adult clients 24 hours before blood collection (Alcohol in the blood changes lipid levels, the level of glucose is reduced, uric acid levels increase and liver enzymes are released into the blood),
• take only prescribed medicines in the evening,
• avoid increased physical activity, and strength and endurance exercise the day before blood collection (Lipid, glucose, some enzyme levels in the blood and other parameters may change during physical activity. The recovery of normal values to maintain the accuracy of laboratory results may take a longer time, depending on the duration of the exercise, your physical fitness in general and other factors. We recommend maintaining normal daily physical activity such as light stretching, short cycling to work, gardening, etc.),
• avoid psychological stress, which raises blood glucose levels and causes the release of stress hormones in particular,
• avoid smoking for at least 6 hours prior to blood collection because it increases the level of carbonylhemoglobin produced by the reaction of the blood dye with carbon monoxide and alters the permeability and elasticity of the vessels, affecting the ratios of blood analytes,
• do not chew gum for at least 6 hours before blood collection, as this may affect glucose and enzyme levels,
• do not undergo stressful diagnostic or therapeutic interventions for at least 24 hours prior to blood collection.
If any of the tests you have selected require special preparation, you will be informed of the fact by email with the order and blood collection instructions attached. These specific instructions have priority over the general recommendations for preparation.
MEDICINES
It is recommended to have blood collected before the planned doses of medicines. If it is not possible to take the medicine later, you should inform the nurse during blood collection and specify what medication you have taken.
Take the medicines prescribed by your doctor in the morning or bring them with you to take them after blood collection (thyroid medicines, antihypertensive medicines, blood thinners, contraceptives, etc.) In the case of later collection (after 9:30 a.m.), you can take the prescribed medication in the morning.
Do not take iron, vitamin, nutritional supplements or other supplements, including homeopathics, for at least three (3) days prior to blood collection.
SPECIFIC SITUATIONS
In order to obtain the appropriate answers to your questions with regard to the laboratory tests, it is important to accurately notify the nurse at the healthcare provider about the following facts prior to your blood test:
• regularly used medicines and supplements (ideally come with a written list to the blood collection site),
infectious diseases you suffer from (e.g., HIV, hepatitis, mononucleosis...),
• contact with an infected person or presence in an infectious environment,
• if you have received an infusion within the last 5 days, specify into which limb,
• intramuscular injections within 3 days prior to the blood collection date,
• long-term immobilisation, lost ability to move,
• activities at higher altitudes,
• allergy to common band-aids,
• if you feel unwell when looking at blood or needles, please also notify our blood collection staff of the fact.
OTHER FACTORS
Please note that prolonged use of medication or other important factors may affect the values measured by the tests you have selected. For more information, please see the description of the specific test. To obtain objective test results, take the time to properly prepare for your blood collection.
Sources
(1) Hrubisko, M., Danis, R., Huorka, M., & Wawruch, M. (2021). Histamine Intolerance—The more we know the less we know. A review. Nutrients, 13(7), 2228. Dostupné online na: https://doi.org/10.3390/nu13072228. [cit. 18-09-2024].
(2) Arih, K., Đorđević, N., Košnik, M., & Rijavec, M. (2023). Evaluation of serum diamine oxidase as a diagnostic test for histamine intolerance. Nutrients, 15(19), 4246. Dostupné online na: https://doi.org/10.3390/nu15194246. [cit. 18-09-2024].
(3) Cucca, V., Ramirez, G. A., Pignatti, P., Asperti, C., Russo, M., Della-Torre, E., Breda, D., Burastero, S. E., Dagna, L., & Yacoub, M. (2022). Basal serum diamine oxidase levels as a biomarker of histamine intolerance: a Retrospective cohort study. Nutrients, 14(7), 1513. Dostupné online na: https://doi.org/10.3390/nu14071513. [cit. 18-09-2024].
(4) Kovacova-Hanuskova, E., Buday, T., Gavliakova, S., & Plevkova, J. (2015). Histamine, histamine intoxication and intolerance. Allergologia Et Immunopathologia, 43(5), 498–506. Dostupné online na: https://doi.org/10.1016/j.aller.2015.05.001. [cit. 18-09-2024].
(5) Histamine intolerance. (2024). Cleveland Clinic. Dostupné online na: https://my.clevelandclinic.org/health/diseases/histamine-intolerance. [cit. 18-09-2024].
(6) Comas-Basté, O., Sánchez-Pérez, S., Veciana-Nogués, M. T., Latorre-Moratalla, M., & Del Carmen Vidal-Carou, M. (2020). Histamine intolerance: the current state of the art. Biomolecules, 10(8), 1181. Dostupné online na: https://doi.org/10.3390/biom10081181. [cit. 18-09-2024].
(7) Reese, I., Ballmer-Weber, B., Beyer, K., Fuchs, T., Kleine-Tebbe, J., Klimek, L., Lepp, U., Niggemann, B., Saloga, J., Schäfer, C., Werfel, T., Zuberbier, T., & Worm, M. (2017). German guideline for the management of adverse reactions to ingested histamine. Allergo Journal International, 26(2), 72–79. Dostupné online na: https://doi.org/10.1007/s40629-017-0011-5. [cit. 18-09-2024].
(8) Ezema, J. N., Agbo, E. C., & Eze, E. A. (2021). Microbial production of histamine and the imperatives of processed food consumption. Bio Research Journal/Bio- Research, 19(2), 1317–1327. Dostupné online na: https://doi.org/10.4314/br.v19i2.5. [cit. 18-09-2024].
(9) Leitner, R., Zoernpfenning, E., & Missbichler, A. (2014). Evaluation of the inhibitory effect of various drugs / active ingredients on the activity of human diamine oxidase in vitro. Clinical and Translational Allergy, 4(S3). Dostupné online na: https://doi.org/10.1186/2045-7022-4-s3-p23. [cit. 18-09-2024].
(10) Schnedl, W. J., Lackner, S., Enko, D., Schenk, M., Holasek, S. J., & Mangge, H. (2019). Evaluation of symptoms and symptom combinations in histamine intolerance. Intestinal Research, 17(3), 427–433. https://doi.org/10.5217/ir.2018.00152. [cit. 18-09-2024].
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