If you have lactose intolerance and also extra–digestive symptoms (migraine, pruritus, rhinitis, fatigue, etc.), you could have diamine oxidase (DAO) deficiency as well.

Histamine is found in a wide variety of foods, both of vegetal and animal origin, and acts on different body systems. Lactose, as its name suggests, is found in dairy products, or derivatives thereof, and in some processed foods or medicines. When there is a DAO enzyme or a lactase enzyme deficiency, their respective substrates (histamine and lactose) will not be able to be metabolized correctly and symptoms may appear. In the case of lactose intolerance, they usually appear a few hours after the food is ingested, on the other hand, in the case of DAO deficiency, they can take more hours, even 24h.

On the one hand, the DAO enzyme is responsible for metabolizing histamine from food into imidazole acetic acid. This enzyme is synthesized in the cytoplasm and in the mitochondria of enterocytes (duodenum and ileum) and is mainly located in the small intestine, kidneys, and placenta. It is estimated that the prevalence of DAO deficiency reaches 15% of the world population. If there is a DAO deficiency an absorption of food histamine is generated, when in reality, the histamine should not be absorbed, but expelled through the urine. When this histamine enters the bloodstream it activates a series of receptors distributed in different tissues of the body and, consequently, digestive symptoms, but also extra-digestive symptoms can appear.

On the other hand, the lactase enzyme is responsible for metabolizing lactose into glucose and galactose. In the same way as the DAO enzyme, this enzyme is also synthesized in the small intestine, although it is found more in the microvilli area of the enterocytes of the proximal jejunum (85%), like the rest of the disaccharide enzymes. However, lactase deficiency generates an increase in hydrogen in the colon whose symptoms are exclusively digestive, unlike DAO deficiency.

In this way, since the DAO enzyme and lactase are synthesized in the intestinal villi, an atrophy of these can cause a deficiency of both, as well as of other enzymes. Therefore, there may be patients with lactose intolerance who do not improve completely. This fact can give rise to a secondary DAO deficiency.

There is scientific evidence linking both aspects:

• In 1984, a Belgian researcher saw that the lower lactase activity at the intestinal level, the lower DAO activity was also (Forget, P. et al, 1984).
• Decades later, in 2016, another Austrian researcher measured the amount of hydrogen in patients who had lactose intolerance. He divided the sample into two groups: one had a correct DAO activity level and the other group suffered DAO deficiency. After the 60 minute, the group who presented lactose intolerance and DAO deficiency produced a greater amount of hydrogen, so they concluded that they had worse health of the intestinal tract (Enko et al, 2016).
• Recently, in 2020, another group of German researchers compared three groups of patients: a group with lactose intolerance, a second group of patients with lactose intolerance + DAO deficiency, and a third with DAO deficiency + fructose malabsorption. The groups which generated the highest amount of expired hydrogen were those that presented the greatest damage of the intestinal villi (Schnedl et al, 2020).

Primary or secondary DAO deficiency should be suspected if, in addition to digestive symptoms, there are one or more symptoms in different systems. In this case, the next step would be to analyze the genetic variants of the AOC1 gene which code for the synthesis of the DAO enzyme, as well as the DAO activity in serum. If the result were positive and lactose intolerance was present, the treatment to follow would be a lactose-free and low-histamine diet, supplemented with lactase and DAO enzyme so that it would not be so restrictive.

In conclusion, a lactase and DAO enzyme deficiency can cause digestive and extra-digestive symptoms if they go hand in hand. Once diagnosed, the synergy between diet and supplementation helps the patient improve their quality of life in a shorter time. For this reason, it is important that health professionals update themselves in order to correctly detect and treat both digestive pathologies.

If you are interested in this topic, you can view the webinar which Adriana Duelo gave with the Lactose Intolerance Spanish Association through the following link.

Bibliography

Enko, D., Meinitzer, A., Mangge, H., Kriegshäuser, G., Halwachs-Baumann, G., Reininghaus, E. Z., Bengesser, S. A., & Schnedl, W. J. (2016). Concomitant Prevalence of Low Serum Diamine Oxidase Activity and Carbohydrate Malabsorption. Canadian journal of gastroenterology & hepatology, 2016, 4893501. https://doi.org/10.1155/2016/4893501

Enko, D., Kriegshäuser, G., Halwachs-Baumann, G., Mangge, H., & Schnedl, W. J. (2017). Serum diamine oxidase activity is associated with lactose malabsorption phenotypic variation. Clinical biochemistry, 50(1-2), 50–53. https://doi.org/10.1016/j.clinbiochem.2016.08.019

Forget, P., Grandfils, C., van Cutsem, J. L., & Dandrifosse, G. (1984). Diamine oxidase and disaccharidase activities in small intestinal biopsies of children. Pediatric research, 18(7), 647–649. https://doi.org/10.1203/00006450-198407000-00016

Schnedl, W. J., Meier-Allard, N., Lackner, S., Enko, D., Mangge, H., & Holasek, S. J. (2020). Increasing Expiratory Hydrogen in Lactose Intolerance Is Associated with Additional Food Intolerance/Malabsorption. Nutrients, 12(12), 3690. https://doi.org/10.3390/nu12123690