General Precision Point Diagnostics April 9, 2024

With the upcoming World DAO Congress coming up, we thought we would take some time to communicate the importance of DAO (Diamine Oxidase) as a marker of clinical relevance for your patients. Precision Point Diagnostics is the only lab in the United States that tests DAO. Dr. Cheryl Burdette, a Precision Point founder and our education director, is happy to have been invited to be part of the World DAO Congress, taking place virtually, hosted from Barcelona, Spain, and free for all. 

Precision Point Diagnostics includes DAO testing as part of our Advanced Intestinal Barrier Assessment. The Advanced IBA profile stands out for its unique, clinically relevant markers which tell a complex story about gut barrier health. Histamine and diamine oxidase (DAO) give information about histamine balance and gut mucosal health. Plasma Zonulin is a well-documented marker of intestinal tight junctions and is the preferred specimen for assessment. Lipopolysaccharides (LPS) are endotoxins produced by gram-negative bacteria. LPS antibodies give information about inflammation and intestinal permeability. Patients with allergies, food sensitivities, digestive symptoms, headaches, cognitive decline, depression, and more can benefit from the Advanced IBA profile.

Based on the results of the Advanced IBA profile, clinicians can tailor specific treatment protocols for their patients and monitor progress over time. Protocols to improve intestinal permeability are not one-size-fits-all. The Advanced IBA profile helps to identify the root cause of barrier dysfunction so that treatment is speedy, cost-effective, and successful. Some patients need to address DAO and histamine balance. Others need to address the root causes of Zonulin elevation or high LPS antibodies. With the Advanced IBA profile, you can pinpoint and treat the causes of intestinal permeability and get your patients back on the road to wellness.

Some labs will test histamine tolerance, but not include DAO assessment. Why do we test DAO specifically? Histamine and DAO exist together in a relationship that affects one another. Histamine intolerance can develop when a person has abnormal levels of histamine and the histamine-degrading enzyme, diamine oxidase. Typical symptoms of histamine intolerance are headache, diarrhea, migraine, general inflammation, circles under the eyes, and runny nose. Histamine intolerance might be more obvious with specific food triggers leading to asthma and arrhythmia, hypotension, urticaria, and dysmenorrhea. When DAO or histamine is imbalanced, the main focus of treatment is to increase DAO, reduce histamine, and heal the gut. Tests that only examine histamine levels miss out on the role that DAO plays in the regulation of histamine. Only by knowing both histamine and DAO levels can an effective treatment plan be crafted.

Histamine balance is a critical factor in patients with allergic and gastrointestinal symptoms. Neither too high nor too low of a level of Histamine is desirable. Histamine was first discovered in its role in anaphylactic allergy. A specific allergen can trigger the degranulation of mast cells, subsequently releasing histamine. This can lead to severe, life-threatening symptoms. When the gut barrier is weakened, a person is more vulnerable to food antigens, toxins, and unfriendly microbes. A leaky gut tears down the body’s defenses and opens the system up to increased inflammation.

After extreme histamine exposure, as in anaphylactic shock, levels of both diamine oxidase and histamine will be elevated. Low histamine levels may cause fatigue or depression. Alterations of histamine have been noted in sleep-wake disorders such as narcolepsy, as well as other neurological and psychiatric diseases. Brain levels of histamine are decreased in Alzheimer’s and low histamine has been seen in cases of convulsions and seizures.

Diamine Oxidase (DAO) is histamine’s vital counterpart and the primary enzyme responsible for keeping histamine levels in check. DAO degrades extracellular histamine and is mainly produced in the microvilli of the small intestine. When diamine oxidase is low it means the patient cannot properly break down histamine. Histamine-N-methyltransferase (HNMT) is the secondary enzyme involved in Histamine breakdown. Low Diamine Oxidase is associated with headaches, fatigue, hives, any allergy symptoms, dysmenorrhea, estrogen dominance, arrhythmia, inflammation, arthritis, and certain neurologic conditions such as multiple sclerosis. Symptoms of low DAO are essentially identical to symptoms of histamine excess because they are two sides of the same coin. In fact, diamine oxidase supplementation has been found to improve symptoms in patients with histamine intolerance.

Low levels of DAO correlate with poor mucosal integrity and indicate poor gut function. Atrophy of the microvilli can cause low DAO. “The serum level of diamine oxidase (DAO) reflects the integrity and maturation of the small intestinal mucosa. This measure is important in diagnosing various diseases, including chronic urticaria tachyphylaxis, multiple organ dysfunction syndrome, preterm abortion, and migraine”. Patients suffering from diseases like urticaria, Crohn’s, or celiac disease are reported to show low DAO activity in serum or plasma. Low DAO can also be a trigger for depression or anxiety. Many medications inhibit DAO or damage the gut lining, reducing DAO production. Alcohol and its degradation product, acetaldehyde, are inhibitors of DAO. 

The DAO: Histamine Ratio helps detect even subtle imbalances between Histamine and DAO levels. Even if the DAO enzyme level is normal, symptoms can occur when Histamine is high. A low ratio indicates that there may not be enough of the DAO enzyme relative to the amount of Histamine in the body. The Precision Point Diagnostic Advanced IAB test reports not only levels of histamine and DAO but also the DAO: Histamine ratio. 

In the metabolism of histamine, when it should be degraded by DAO enzyme in order to become N-acetyl aldehyde imidazole, an accumulation of the amine is produced due to the lack of enzyme in the intestinal mucosa cells. Low enzyme activity causes the concentration of histamine, which comes from the food and is generally considered normal, not to be metabolized and a transepithelial permeation of exogenous histamine occurs.
This way, histamine enters the bloodstream increasing its plasma concentration and once located in blood it spreads throughout the body” Because of DAO’s implication in inflammation, and as explained above, not just in the gut but systemically, there is emerging evidence that  DAO can indicate other disease states as well that are related to histamine regulation and inflammation in general. Indeed, measuring DAO levels can be an additional method for assessing systemic inflammation in a patient that stems from gut dysbiosis. If you haven’t as yet, give the Precision Point Diagnostic Advanced Barrier Assessment a try. Also, don’t forget to join the free presentations at the Global DAO Congress on April 11th, 2024!

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