Wisdom Wednesday: DAO Deficiency

Diamine oxidase (DAO) is the major enzyme involved in histamine metabolism and is responsible for ensuring a steady histamine level required for the balance of numerous chemical reactions taking place in the body.

DAO is the key enzyme responsible for the degradation of extracellular (free) histamine, regardless of whether the histamine originates from allergy-induced processes in the body or is consumed with food.

Histamine exerts its effects by binding to its 4 receptors: H1R, H2R, H3R and H4R on target cells in various tissues. Histamine receptors are located all over the body and have many important functions including:

• H1 receptors: Smooth muscle and endothelial cells affecting skin; blood vessels (Benadryl and Claritin block activity of these receptors)
• H2 receptors: Cells in the intestines control acid secretion, abdominal pain, and nausea; heart rate
• H3 receptors: Central nervous system controlling nerves, sleep, appetite and behavior.
• H4 receptors: Thymus, small intestine, spleen, colon, bone marrow and white blood cells; inflammatory response

The DAO gene is also involved in the metabolism of glutamate, an excitatory neurotransmitter found to be elevated in those with schizophrenia and bipolar disorders. The DAO snippet can be identified in genetic testing, like 23andme. If you have a primary deficiency it can lead to significantly reduced DAO enzyme activity. Individuals with a DAO gene mutation may have a tendency towards high histamine.

The DAO enzyme is dependent on vitamin B6, B12, iron, copper and vitamin C. Excess zinc will prevent copper absorption and may also be an issue in the diet.



Small Intestinal Bacterial Overgrowth (SIBO), Leaky Gut Syndrome, GI inflammatory conditions, like Crohn’s disease, IBS, colitis and Celiac disease all produce high amounts of histamine that can alter DAO production. Certain drugs like NSAIDs, PPIs, anti-depressants, and immune suppressants also can suppress DAO production.

Few companies produce DAO supplements and have difficulty obtaining the raw materials for consistent production. However, DAO naturally occurs in pea sprouts and to a lesser extent, pea protein.

Pea protein has become more popular the last few years as people look for a protein powder other than whey, casein or soy. Both Standard Process and Biotics now have a pea protein powder used in their detoxification programs.

I have begun using pea protein in patients who persist with digestive issues despite having corrected other aspects of digestion, inflammation, and dysbiosis. The early results are encouraging.

Using myself as a guinea pig, I find significant reduction in mucous congestion especially upon arising in the morning. I actually reduced the dose from daily to three days a week as the anti-histamine effects felt too “drying” to the digestive and respiratory tracts. My wife, who is lactose intolerant, has noted a dramatic improvement in bowel function and prefers to take the pea protein almost daily.

The Bottom Line:
If you have unresolved digestive issues and/or excessive histamine production, try pea protein as a short term change to your diet. You should note some benefit within just a few days. Then modify the dosage as needed. For those who want definitive testing, Dunwoody Labs in Georgia offers a plasma test that measures DAO, histamine and zonulin along with IgA, IgG and IgM LPS to evaluate the intestinal barrier.