Diamine oxidase (DAO) is an enzyme that your body uses to break down ingested histamine. There are a wide variety of foods that contain histamine, and it is DAO’s job to break this histamine down. DAO also helps with the integrity of the gut lining, protecting us from leaky gut and the functional digestive issues that can precipitate from it.
Histamine, in addition to being found in foods, is a compound that is released from the immune system. Histamine is responsible for those classic allergic-like reactions: watery, itchy eyes and nose, hives, skin rash, even wheezing.
DAO is found in very high concentrations in certain places – namely, the small intestine, the first part of the large intestine, and the kidneys. Its job is to break down the histamine that we eat. If it cannot break it down because the enzyme doesn’t work, or if we do not have enough DAO on board, histamine is not broken down and begins to accumulate. Then, we can experience symptoms from excessive histamine and in some people, histamine intolerance.
These types of reactions mimic allergic reactions, making it difficult to tease out the two separately, but there is a difference. People with DAO insufficiency and/or histamine intolerance do not show IgE levels to foods. In other words, their skin prick tests are negative, but they still have allergic-type reactions to foods.
Symptoms can include diarrhea, headache, itchy eyes and nose, asthma, wheezing after eating, low blood pressure, dizziness after eating, heart arrhythmias, hives, dermatitis around the mouth, itching and skin flushing. These symptoms appear similar to food allergy, sensitivity to sulfites and other “amine” compounds like tyramine.
Diagnosable conditions where DAO is diminished include Crohn’s disease, Ulcerative Colitis (thus it makes sense DAO would be diminished in other inflammatory bowel conditions) and allergic enteropathy. Normal blood levels of histamine are between 0.3-1.0 ng/ml, and a level over 10 ng/ml should be strongly considered as histamine intolerance/DAO insufficiency, although at this time it is still a theoretical jump, albeit one that makes sense.
It is estimated that 1% of the population has histamine intolerance, and that 80% of those people are middle-aged, suggesting that this intolerance is something that we develop over time rather than born with. What is less clear is how many people have DAO insufficiency and/or a lack of DAO production. Another wrench thrown into the works is that it appears that histamine intolerance is transient in some people, meaning that it doesn’t last.
Foods that are high in histamine include fermented foods like hard cheese, yogurt, kefir, beer, wine, sauerkraut and certain meat products, spinach and tomatoes. Citrus – lemons, limes, oranges, tangerines and grapefruit – are histamine liberators, meaning they stimulate the release of histamine. In people with suspected DAO impairment or histamine intolerance, there should be a trial period where these foods are avoided to see if symptoms improve.
Monoamine oxidase inhibitors (MAOI) inhibit the breakdown of dietary amines, including histamine and tyramine. In addition to contributing to histamine overload, these drugs can also drive blood pressure dangerously high when tyramine rich foods are consumed. MAOI drugs are typically the antidepressants Isocarboxazid (Marplan), Phenelzine (Nardil), Selegiline (Emsam, Eldepryl, Zelapar), Tranylcypromine (Parnate). Other drugs have MAOI activity such as Zoloft, Bupropion, Paxil, Prozac, Effexor, Celexa, Lexapro, Tranylcypromine and Phenelzine. Other drugs that can release histamine or inhibit DAO include some muscle relaxants, Thiopental, Morphine, NSAIDs, Verapamil, alprenolol, dihydralazine, Propafenone, Amiloride, Metoclopramide, certain antibiotcs (cefuroxime, cefotiam, Isoniazid, choroquine), Acetylcysteine, ambroxol, Cimetidine and Cyclophosphamide.
Hormones can play a role as well. Histamine stimulates estradiol, so women who get headaches or migraines around menses may have histamine intolerance.
If histamine intolerance is suspected, the best approach to take is a trial intervention to see if symptoms improve. Diagnosis can be tricky. If IgE allergies are not present, and other systemic diseases have been ruled out, and these symptoms are present, an intervention is warranted. An intervention is warranted particularly if there is a diagnosis of inflammatory bowel disease.
Since it is virtually impossible to avoid all foods that contain histamine, emphasis should be placed on the foods listed above: fermented foods and beverages, tomatoes, spinach and citrus. Concurrently, DAO should be taken 15-20 minutes before each meal. It is important to take DAO before meals, so it is in place, rather than during or after meals. DAO is typically derived from animal sources, so it is not appropriate for vegetarians. Additionally, antihistamine and immune-cell stabilizing nutrients should be taken daily, including Vitamin C, Vitamin B6 and bioflavonoids. A broad-spectrum enzyme product, containing a variety or proteases, is also recommended. This intervention should remain in place for 4 weeks minimum to see if improvement is noted. If improvement is seen, we can suspect histamine intolerance. Histamine intolerance can be transient, so periodically histamine-containing foods should be rotated into the diet as a challenge to see if the body has the same response.
DAO insufficiency and histamine intolerance, though not common, could be the reason why some people still have allergy-type reactions to foods in spite of not having food allergy. It is worth the exploration.