DAOplus: How the DAO enzyme helps prevent chronic disease development - Synlab

DAOplus: How the DAO enzyme helps prevent chronic disease development

Published by Synlab on 22 April 2021
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The diamine oxidase (DAO) enzyme is the main intestinal enzyme involved in the metabolism of histamine, and its deficiency is related to different chronic diseases. Histamine is present in several foods and is rapidly degraded when the individual has normal DAO activity. However, for individuals with reduced activity, there is an excess of histamine in the blood, thus increasing the probability of presenting several clinical conditions often associated with chronic diseases, due to the deficit in the DAO enzyme.  


Histamine and its consequences  

Histamine is present in different concentrations in many foods. The consumption of foods rich in histamine, such as: 

  • Canned fish 
  • Cheeses 
  • Sausages 
  • Spinach 
  • Tomato 
  • Avocado 
  • Eggplant 
  • Pickles 
  • Banana 
  • Kiwi 
  • Strawberry 
  • Citrus fruits  
  • Chocolate 
  • Peanut 
  • Hazelnut  
  • Nuts 
  • Balsamic vinegar 
  • Red wine 
  • Champagne 
  • Fermented beers (wheat beer) 
  • Whisky 
  • Brandy 
  • Liquor 

And they can cause different symptoms, such as: 

  •      diarrhea       
  • headache  
  • hypotension  
  • arrhythmia  
  • hives  
  • itching            
  • flushing      


in addition,      several drug products can induce the release of histamine or block the activity of the DAO enzyme, which acts as the main enzyme in histamine metabolism.  

Excess histamine in the blood increases the likelihood that the individual will have a condition known as histamine intolerance.  


Histamine intolerance 


Histamine intolerance results from an imbalance in the accumulation of histamine and its degradation capacity. 


Because several factors that intervene in the presentation and intensity of the symptoms in histamine intolerance, and the misinterpretation of these symptoms, the prevalence of this syndrome is underestimated. It is suggested that approximately 1% of the population have histamine intolerance and that 80% of affected patients are middle-aged. 


In histamine intolerant patients who have reduced DAO      enzyme activity, symptoms occur even after ingesting small amounts of histamine, these being well tolerated by healthy people. Symptoms can be manifested by the actions of histamine mentioned above in multiple organs, such as the gastrointestinal system, lungs, skin, cardiovascular system and brain. 

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

Histamine and headache  

Headache is the main symptom of individuals with histamine intolerance. It can be induced by histamine both in healthy individuals and in individuals who already experience migraines.  

Histamine-induced headache is a vascular headache caused mainly by nitrate monoxide, which is released in the endothelium by stimulation of the histamine receptor (H1R), which is also expressed in the large intracranial arteries. It was observed in patients with migraines, high plasma histamine concentrations during flares and periods without symptoms.  

Read more about the relationship between histamine and migraine flares in our article: DAO enzyme: a promising key for the treatment of migraines 

Histamine and gastrointestinal disorders 

Followed by headache, gastrointestinal disorders, including diffuse stomach pain, cramps, flatulence and diarrhea, are the main symptoms of histamine intolerance.  

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

  • Crohn’s disease: Inflammatory disease of the gastrointestinal tract, which mainly affects the ileum and colon. The most common symptoms include: diarrhea, abdominal colic, fever, and rectal bleeding.  


  • Ulcerative colitis: Chronic inflammatory bowel disease where there is colon inflammation with ulcers, causing episodes of bloody diarrhea, abdominal cramps and fever. It presents a higher long-term risk of developing colon cancer.  


  • Colorectal neoplasms: It was found that, in patients with adenocarcinoma, the DAO     enzyme activity was reduced in the tumor itself compared to the adjacent histologically normal mucosa.       


Histamine and atopic eczema 

Eczema is an acute or chronic inflammation of the skin that is identified by the appearance of itching, swelling and redness. It is usually found in the arms, behind the knees and skin in general.  

Elevated baseline plasma concentrations of histamine and increased release were seen in patients with severe atopic eczema when compared to patients without the condition. Reduced DAO enzyme activity has also been seen in patients with severe atopic eczema.  

Histamine and steroidal hormones  

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

Histamine has been shown to stimulate estradiol synthesis via H1R. Severe menstrual cramps are caused mainly by an increase in the production of prostaglandin F2 mucosa stimulated by estradiol and attenuated by progesterone.  

Thus, histamine can increase dysmenorrhea, increasing estrogen concentrations. Conversely, estrogen can influence the action of histamine. A significant increase in skin reactions was observed, such as the size of the papule and rash in response to histamine, being correlated with ovulation and the peak of estrogen concentrations 

During pregnancy, the DAO enzyme is produced in high concentrations by the placenta, and its concentration can reach 500 times  that of a non-pregnant woman. This increase in DAO enzyme production in pregnant women may explain why women with food intolerance experience remissions during pregnancy 



What does DAOPlus – SYNLAB Innovation test – detect? 

The DAOPlus test performs the analysis of the enzyme diamine oxidase (DAO) activity. The identification of enzymatic activity can be evaluated as an intrinsic factor triggering chronic diseases, enabling an effective preventive treatment of the disease, with significant improvement in the patient’s quality of life. 

Who is the test indicated for? 

The DAO PLUS test is especially indicated for: 

  • Migraine and other vascular headaches;
  • Gastrointestinal disorders: especially those associated with Irritable Bowel Syndrome (IBS), such as constipation, diarrhea, satiety, flatulence or bloated feeling;
  • Dermatological disorders: such as dry skin, atopy or psoriasis;
  • Bone disorders: such as osteopathic pain; 
  • Muscle changes: such as muscle pain, often diagnosed as fibromyalgia;
  • Chronic fatigue;
  • In childhood and adolescence it is related to attention-deficit/hyperactivity disorder, and to Cyclic Vomiting Syndrome.

Histamine intolerance and DAOPlus: Targeting the best treatment 

Many patients who have histamine intolerance, as evidenced by reduced activity of the DAO     enzyme, with the onset of flares due to histamine-rich foods, may experience symptom relief with a histamine-free diet, antihistamine therapy, DAO supplement or combination of these treatments. 

The DAOPlus test analyses the enzyme activity of diamine oxidase (DAO), making it possible to recognize one of the main reasons for histamine      intolerance and thereby assist the physician in choosing the best treatment for the individual.  


Read more about the SYNLAB DAO enzyme activity analysis test here. 


About the SYNLAB Group 

The SYNLAB Group is a leader in providing medical diagnostic services in Europe, providing a full range of clinical laboratory analysis services to patients, healthcare professionals, clinics and the pharmaceutical industry. Resulting from the Labco and Synlab merger, the new SYNLAB Group is the undisputed European leader in medical laboratory services. 

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