Enzyme Biomarkers: Diamine Oxidase (DAO)

Optimal Takeaways

Diamine oxidase is a naturally occurring enzyme in the GI tract that breaks down the histamine found in food. Levels in the blood can help evaluate whether someone can adequately break down histamine or whether they are prone to histamine intolerance, a disorder characterized by abdominal bloating, diarrhea, itching, flushing, and headache.

Although supplemental DAO can help break down ingested histamine, avoidance of high-histamine foods is often necessary for best clinical management.

Standard Range: 3 - 10 U/mL

The ODX Range: 10 - 100 U/mL          

Low levels of DAO are associated with histamine intolerance, single nucleotide polymorphisms (Manzotti 2016), possibly copper insufficiency (DiNicolantonio 2018), IBD IBS, gastroenteritis, carbohydrate malabsorption, non-celiac gluten sensitivity, migraines, alcohol use, and certain medications, including chloroquine, verapamil, clonidine, and metoclopramide (Comas-Basté 2020).

High DAO activity likely represents the ability to adequately break down extracellular histamine.

Overview

Diamine oxidase (DAO) is a gastrointestinal enzyme that primarily breaks down food-derived histamine, though it also breaks down other bioactive amines such as putrescine and cadaverine. Histamine is produced by bacteria, and foods high in histamine include fermented foods, fermented beverages, cured meats, sausage, canned fish, and food that is aging or spoiled (Comas-Baste 2020). 

Histamine intolerance (HIT) occurs when insufficiency of DAO leads to a buildup of histamine causing a variety of symptoms, including headache, abdominal pain and bloating, diarrhea, asthma, hypotension, rhinoconjunctivitis, arrhythmia, itching, and flushing. In one study of suspected histamine intolerance among 14 non-IgE mediated allergy patients, researchers found that those diagnosed with histamine intolerance (10 of the 14) had a DAO activity level below 10 U/mL. Low levels of DAO indicate a decreased ability to break down histamine that is ingested or generated by alcohol or medications that stimulate histamine release or may block the DAO enzyme. Single nucleotide polymorphisms can inhibit DAO production and increase histamine intolerance. A DAO activity level below 10 U/mL is likely associated with histamine intolerance while a level 3 is highly likely to reflect histamine intolerance (Manzotti 2016).

The most severe symptom of histamine intolerance is likely to be abdominal bloating with frequent complaints of fullness following meals, diarrhea, and abdominal pain, as well as constipation in some individuals. Headache or migraines are also reported. The presence of these symptoms, along with a serum DAO activity below 10 U/mL and relief following a low histamine diet, makes a diagnosis of histamine intolerance more likely. Histamine intolerance may overlap with other gastrointestinal disorders including, celiac disease, dysbiosis, and SIBO (Schnedl 2021). Reduced DAO is also observed in inflammatory bowel disease and low serum levels may reflect increased intestinal permeability (Honzawa 2011).

A low-histamine diet can provide relief from histamine intolerance symptoms and may even increase serum levels of DAO. Consuming adequate cofactors for DAO production may also improve HIT symptoms, these include vitamin B6, vitamin C, and copper (Hrubisko 2021).

Histamine intolerance caused by medication or other external cause may resolve once the cause is removed. However, in those with a genetic propensity or other gastrointestinal disorder, intolerance may be chronic. Supplemental DAO from porcine or vegetarian sources is available for persistent symptoms and can help break down ingested histamine (Schnedl 2019, Comas-Basté 2020). 

References

Comas-Basté, Oriol et al. “Histamine Intolerance: The Current State of the Art.” Biomolecules vol. 10,8 1181. 14 Aug. 2020, doi:10.3390/biom10081181

DiNicolantonio, James J et al. “Copper deficiency may be a leading cause of ischaemic heart disease.” Open heart vol. 5,2 e000784. 8 Oct. 2018, doi:10.1136/openhrt-2018-000784

Honzawa, Yusuke et al. “Clinical significance of serum diamine oxidase activity in inflammatory bowel disease: Importance of evaluation of small intestinal permeability.” Inflammatory bowel diseases vol. 17,2 (2011): E23-5. doi:10.1002/ibd.21588

Hrubisko, Martin et al. “Histamine Intolerance-The More We Know the Less We Know. A Review.” Nutrients vol. 13,7 2228. 29 Jun. 2021, doi:10.3390/nu13072228

Manzotti, G et al. “Serum diamine oxidase activity in patients with histamine intolerance.” International journal of immunopathology and pharmacology vol. 29,1 (2016): 105-11. doi:10.1177/0394632015617170

Mušič, Ema et al. “Serum diamine oxidase activity as a diagnostic test for histamine intolerance.” Wiener klinische Wochenschrift vol. 125,9-10 (2013): 239-43. doi:10.1007/s00508-013-0354-y

Schnedl, Wolfgang J et al. “Diamine oxidase supplementation improves symptoms in patients with histamine intolerance.” Food science and biotechnology vol. 28,6 1779-1784. 24 May. 2019, doi:10.1007/s10068-019-00627-3

Schnedl, Wolfgang J, and Dietmar Enko. “Histamine Intolerance Originates in the Gut.” Nutrients vol. 13,4 1262. 12 Apr. 2021, doi:10.3390/nu13041262