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DAO Deficiency- How To Activate The Enzyme That Reduces Histamine Intolerance and MCAS Symptoms.

A common cause of histamine intolerance and Mast Cell Activation Syndrome (MCAS) is a deficiency in DAO. DAO stands for Diamine oxidase and when this enzyme is deficient, histamine builds up in the body causing a variety of symptoms. While women are more vulnerable to the symptoms of histamine intolerance and MCAS, anyone with DAO deficiency can experience hives (urticaria), Asthma, Migraines, low blood pressure, GI disorders such as IBS, IBD, eosinophilic esophagitis, painful menstrual cramps, Depression, Anxiety should consider this as a potential contributor.

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Before we jump into the steps to increase DAO enzyme activity, it is imperative to understand that there could be many causes for DAO Deficiency, In this article, we will discuss how certain vitamin deficiencies impair DAO enzyme.


Typically, people with DAO deficiency will benefit from supplements that activate the DAO enzyme. Including these vitamins and minerals along with changes in your diet will promote the DAO enzyme and maximize the chance of supporting it for proper function.

It is mentionable that vitamin B6, B12, iron, copper, and vitamin C are vitamins that activate the DAO enzyme. Hence, increasing the intake of these vitamins and minerals will not only help breadk down histamine but many of these vitamins help stabilize the Mast cells.

  • Vitamin C

Did you know? Vitamin C, also known as ascorbic acid, is solely responsible for reducing the histamine level in your body. Researches recently revealed that vitamin C is a cofactor of a family of biosynthetic and gene regulatory monooxygenase and dioxygenase enzymes. 2  blood histamine levels are directly correlated to the vitamin C levels, and intake of vitamin C will lead to less histamine in a matter of days. It functions as a cofactor of DAO, just like vitamin B6 does. Vitamin C can be taken at doses of up to 3,000 mg to reduce histamine levels.

  • Vitamin B6

Vitamin B6 is the part of vitamin B, also known as pyridoxine, which is considered as one of the cofactor enzymes in your body. Owing to the fact that some enzymes which contain B6 require enough dose of this compound to activate and run DAO effectively. An inadequate supply of B6 will lead one to suffer from DAO deficiency for the long term. There is also evidence that vitamin B6 may help transport magnesium into cells, possibly by forming a complex between the two. The intake of vitamin B6 often leads to a higher DAO activity

  • Magnesium

Magnesium also plays a prominent role in accelerating the breaking down histamine. Magnesium plays a role in DAO activity and in the activity of HDC (histidine decarboxylase) HDC is an enzyme that makes histamine from histidine, an amino acid. While defining the role of Magnesium in the body, research3 shows that , “Magnesium activates more than 600 enzymes and influences extracellular calcium levels. It is an important cofactor for activating a wide range of transporters and enzymes.”

In order to prevent DAO deficiency, it is suggested to intake an adequate level of Magnesium to regulate the DAO activity without any interruptions. In magnesium deficient rats, DAO activity is decreased to 50% after 8 days of magnesium deficiency and it returns to baseline once magnesium is reintroduced back in to the diet.

  • Copper

Copper deficiency is another possible cause for low DAO activity. Copper is a major cofactor essential for DAO function. Because copper is essential to DAO function, copper levels should be monitored in patients with low DAO activity to avoid further DAO deterioration. If you have been taking Zinc you could have a copper deficency. Zinc levels should be checked at the same time, as zinc prevents intestinal copper absorption.

Symptoms of copper deficiency may include; Anemia, low level of white blood cells called neutrophils (neutropenia), Osteoporosis, Paleness, Hair with less pigment than normal.


Ways to Increase DAO Activity When You suffer with Histamine Intolerance and MCAS

Other Root Causes of Of DAO Deficiency

Addressing the root cause of DAO deficiency can sometimes require further investigation into several other areas of our health. 1 These Areas include;

  • Genetic Variations in DAO SNP
  • Emotional Stress
  • Gut barrier integrity ie leaky Gut,
  • Hormone imbalances
  • SIBO
  • Gut inflammation
  • Gut Dysbiosis
  • Medications
  • Alcohol block DAO enzyme
  • Green Tea block DAO enzyme
  • Black Tea- block DAO enzyme

Boosting DAO Enzyme Activity Naturally| When You Have Histamine Intolerance 7


If you have already taken the histamine intolerance/MCAS quiz and your results showed that you were likely to have Histamine intolerance/MCAS then modifying your diet to include low histamine foods as well as increasing DAO enzyme activity with direct DAO supplementation or by supplementation with the vitamins discussed in today’s article could go a long way in providing relief.

Supplements that help with Low DAO activity and Histamine Intolerance

  1. DAO
  2. B6
  3. B12
  4. iron
  5. magnesium
  6. Liposomal Vitamin C

People who read this article on DAO also read the following articles related to histamine intolerance and MCAS.

  1. Histamine Intolerance understanding how it makes you sick 
  2. How to start a low histamine diet 
  3. Histamine intolerance and Gut Health- Do You have SIBO?
  4. Hormone Imbalances and Histamine Intolerance- How Estrogen Dominance can aggravate Histamine Levels
  5. Best Tips to Address Histamine Intolerance When You Have SIBO
  6. Assess your Risk of Histamine Intolerance and MCAS
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