DAO activity test: How this test helps with histamine intolerance

The diamine oxidase (DAO) enzyme is the main intestinal enzyme involved in histamine metabolism, and its deficiency is associated with various chronic diseases. 

Histamine is present in many foods and is quickly broken down in individuals with normal DAO activity. 

However, in those with reduced DAO activity, excess histamine accumulates in the blood, increasing the likelihood of developing various clinical conditions often linked to chronic diseases due to the DAO enzyme deficit. 

What is histamine? 

Histamine is an amine that acts as a chemical mediator in various biological functions within the body (1). It is synthesized from the amino acid histidine and primarily stored in mast cells and basophils, being released by immune cells in response to stimuli such as allergic reactions, tissue injury, or infections. This leads to the dilation and increased permeability of small blood vessels, resulting in symptoms like redness, swelling, and itching. 

What is histamine used for? 

Histamine is an essential substance that plays multiple critical roles in the body. In the immune system, it regulates inflammatory and hypersensitivity processes, being released mainly by mast cells and basophils during allergic reactions.  

Additionally, it acts as a neurotransmitter in the central and peripheral nervous systems, influencing functions such as the sleep-wake cycle, appetite, hormonal secretion, and even cognitive processes like memory. 

In the digestive system, histamine stimulates the production of hydrochloric acid in the stomach, vital for food digestion. In the circulatory system, it contributes to blood vessel dilation, regulating blood flow and facilitating the inflammatory response.  

Furthermore, it influences immune cell activity, broadly modulating the immune response, and can sensitize nerve endings, intensifying pain perception in inflamed areas. 

The effects of histamine are mediated by different receptor types (H1, H2, H3, and H4), distributed across various tissues, each playing specific roles that highlight its significance in physiology and clinical medicine. 

What foods contain histamine? 

Histamine is present in varying concentrations in many foods (1).  

Some foods rich in histamine include: 

• Canned fish;
• Cheese;
• Processed meats;
• Spinach;
• Tomato;
• Avocado;
• Eggplant;
• Pickles;
• Banana;
• Kiwi;
• Strawberry;
• Citrus fruits;
• Chocolate;
• Peanuts;
• Hazelnuts;
• Wilmots;
• Balsamic vinegar;
• Red wine;
• Champagne;
• Fermented beers (wheat beer);
• Whiskey;
• Brandy;
• Liqueur.

Histamine and Its consequences 

Also can trigger various symptoms, such as: 

• Diarrhea;
• Headache;
• Hypotension;
• Arrhythmia;
• Hives;
• Itching;
• Flushing.

Additionally, various medications can induce the release of histamine or inhibit the activity of the DAO enzyme, which plays a key role in histamine metabolism. 

Excess histamine in the bloodstream increases the likelihood of developing a condition known as histamine intolerance. 

Histamine Intolerance 

Histamine intolerance results from an imbalance between histamine accumulation and its breakdown capacity. 

Because several factors influence the presentation and severity of histamine intolerance symptoms, as well as their misinterpretation, the prevalence of this condition is underestimated (2). It is estimated that approximately 1% of the population has histamine intolerance, with 80% of affected patients being middle-aged. 

What are the symptoms of histamine intolerance? 

In histamine-intolerant patients with reduced DAO enzyme activity, symptoms occur even after ingesting small amounts of histamine, which are well tolerated by healthy individuals. 

Symptoms can manifest in multiple organs, such as the gastrointestinal system, lungs, skin, cardiovascular system, and brain, due to histamine’s actions. 

Typical symptoms of histamine intolerance, associated with reduced DAO enzyme levels, include gastrointestinal disorders, headache, dysmenorrhea, hypotension, arrhythmias, hives, itching, and flushing. 

Histamine and headaches 

Headache is the primary symptom in individuals with histamine intolerance. It can be triggered by histamine in both healthy individuals and those already suffering from migraines. 

Histamine-induced headache is a vascular headache primarily caused by nitric oxide, which is released in the endothelium through stimulation of the histamine receptor (H1R), also expressed in large intracranial arteries. Studies have shown that migraine patients exhibit elevated plasma histamine levels during episodes and symptom-free periods (3). 

Read more about the relationship between histamine and migraine episodes in our article: DAO Enzyme: A Promising Key for Migraine Treatment. 

Histamine and gastrointestinal diseases 

Following headaches, gastrointestinal diseases, including diffuse stomach pain, cramps, flatulence, and diarrhea, are the main symptoms of histamine intolerance. 

Elevated histamine levels and reduced DAO enzyme activity have been detected in various inflammatory and neoplastic diseases of the gastrointestinal tract, such as: 

• Crohn’s Disease: An inflammatory disease of the gastrointestinal tract that primarily affects the ileum and colon. Common symptoms include diarrhea, abdominal cramps, fever, and rectal bleeding (4);
• Ulcerative Colitis: A chronic inflammatory bowel disease where the colon becomes inflamed and ulcerated, causing episodes of bloody diarrhea, abdominal cramps, and fever. It carries a long-term increased risk of developing colon cancer (5);
• Colorectal Neoplasms: In patients with adenocarcinoma, DAO enzyme activity was found to be reduced in the tumor itself compared to the adjacent histologically normal mucosa (6).

Histamine and atopic eczema 

Eczema is an acute or chronic inflammation of the skin, characterized by itching, swelling, and redness. It is commonly found on the arms, behind the knees, and on other parts of the skin. 

Elevated baseline plasma histamine concentrations and increased release have been observed in patients with severe atopic eczema compared to those without the condition (7). Additionally, reduced DAO enzyme activity has been demonstrated in patients with severe atopic eczema (8). 

Histamine and steroid hormones 

In women, histamine is mainly produced by mast cells, endothelial cells, and epithelial cells in the uterus and ovaries. Women with histamine intolerance frequently experience cycle-dependent headaches and dysmenorrhea (severe menstrual cramps). 

Histamine has been shown to stimulate estradiol synthesis via H1R receptors (9). Severe menstrual cramps are primarily caused by increased prostaglandin F2 production in the mucosa, stimulated by estradiol and attenuated by progesterone. 

Thus, histamine can exacerbate dysmenorrhea by increasing estrogen levels. Conversely, estrogen can influence histamine activity. A significant increase in skin reactions, such as papule size and eruptions in response to histamine, has been correlated with ovulation and peak estrogen concentrations (10). 

During pregnancy, the DAO enzyme is produced in high concentrations by the placenta, reaching levels up to 500 times higher than in non-pregnant women (11). This increase in DAO production during pregnancy may explain why women with histamine intolerance experience remissions while pregnant. 

What test does SYNLAB offer to evaluate the DAO enzyme?  

SYNLAB offers the DAO activity test, which analyzes the activity of the diamine oxidase (DAO) enzyme and histamine degradation. Identifying enzymatic activity allows the evaluation of this intrinsic factor as a trigger for chronic diseases, enabling effective preventive treatment and significantly improving the patient’s quality of life. 

Who is DAO activity test recommended for? 

The DAO activity test is particularly recommended for conditions such as: 

• Migraines and other vascular headaches;
• Gastrointestinal disorders, especially those associated with Irritable Bowel Syndrome (IBS), such as constipation, diarrhea, bloating, or fullness;
• Dermatological disorders: such as dry skin, atopy, or psoriasis;
• Bone disorders: such as osteopathic pain;
• Muscular disorders: such as muscle pain, often diagnosed as fibromyalgia;
• Chronic fatigue;
• In children and adolescents, it is associated with attention-deficit hyperactivity disorder (ADHD) and Cyclic Vomiting Syndrome.

Histamine intolerance and DAO activity test: guidance for better treatment 

Many patients with histamine intolerance, evidenced by reduced DAO enzyme activity and symptom triggers from histamine-rich foods, may find symptom relief through a histamine-free diet, antihistamine therapy, DAO supplements, or a combination of these treatments (12, 13). 

The DAO activity test analyzes the enzymatic activity of diamine oxidase (DAO), allowing the identification of one of the main causes of histamine intolerance and thus helping physicians choose the best treatment for each individual. 

Read more about SYNLAB’s DAO enzyme activity analysis test here. 

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Performing accurate and up-to-date tests is essential for precise diagnoses and better treatment planning. SYNLAB is here to support you. 

We offer diagnostic solutions with rigorous quality control for companies, patients, and physicians. Present in Brazil for over 10 years, we operate in 36 countries across three continents and are leaders in service provision in Europe. 

Contact the SYNLAB team and learn more about the available tests. 

References 

1. G. Manzotti, D. Breda, M. Di Gioacchino, S.E. Burastero. Serum diamine oxidase activity in patients with histamine intolerance. Int J Immunopathol Pharmacol. 2016 Mar;29(1):105-11.

2. L. Maintz, N. Novak. Histamine and histamine intolerance. Am J Clin Nutr. 2007;85(5):1185-1196.

3. L.L. Thomsen. Investigations into the role of nitric oxide and the large intracranial arteries in migraine headache. Cephalalgia. 1997;17(8):873-895.

4. W.U. Schmidt, J. Sattler, R. Hesterberg, et al. Human intestinal diamine oxidase (DAO) activity in Crohn’s disease: a new marker for disease assessment?. Agents Actions. 1990;30(1-2):267-270.

5. E. García-Martin, J.L. Mendoza, C. Martínez, et al. Severity of ulcerative colitis is associated with a polymorphism at diamine oxidase gene but not at histamine N-methyltransferase gene. World J Gastroenterol. 2006;12(4):615-620.

6. J. Kusche, T. Biegański, R. Hesterberg, et al. The influence of carcinoma growth on diamine oxidase activity in human gastrointestinal tract. Agents Actions. 1980;10:110-113.

7. J. Ring. Plasma histamine concentrations in atopic eczema. Clin Allergy. 1983;13(6):545-552.

8. G. Ionescu, R. Kiehl. Monoamine and diamine oxidase activities in atopic eczema. Allergy. 1988;43(4):318-319.

9. J. Bódis, H.R. Tinneberg, H. Schwarz, F. Papenfuss, A. Török, V. Hanf. The effect of histamine on progesterone and estradiol secretion of human granulosa cells in serum-free culture. Gynecol Endocrinol. 1993;7(4):235-239.

10. D. Kalogeromitros, A. Katsarou, M. Armenaka, D. Rigopoulos, M. Zapanti, I. Stratigos. Influence of the menstrual cycle on skin-prick test reactions to histamine, morphine and allergen. Clin Exp Allergy. 1995;25(5):461-466.

11. F. Morel, A. Surla, P.V. Vignais. Purification of human placenta diamine oxidase. Biochem Biophys Res Commun. 1992;187(1):178-186.

12. F. Wantke, M. Götz, R. Jarisch. Histamine-free diet: treatment of choice for histamine-induced food intolerance and supporting treatment for chronic headaches. Clin Exp Allergy. 1993;23(12):982-985.

13. A.A. Krabbe, J. Olesen. Headache provocation by continuous intravenous infusion of histamine. Clinical results and receptor mechanisms. Pain. 1980;8(2):253-259.