DAO: the enzyme that intercepts histamine from food

Healthy state

Diamine oxidase DAO (diamine oxidase) An enzyme in the gut wall that breaks down histamine from food before it reaches the blood. (DAO) is an enzyme that needs copper and works with a protein-bound cofactor of its own (a quinone cofactor). It is made mainly by the cells at the tips of the small intestinal villi, that is, by mature cells of the gut lining. There it is stored and released into the gut as needed. It breaks down histamine Histamine A messenger substance of the body that is also found in aged and fermented foods. Too much can cause headache, flushing or diarrhoea. More in the chapter “Histamine intolerance: much searched, little proven” from food before it reaches the blood, making it the first barrier. The second enzyme, HNMT, only works inside cells. More about histamine itself is in the chapter “Histamine”.

DAO breaks down not only histamine but also other biogenic amines such as putrescine and cadaverine. These are often found together with histamine in aged foods and compete for the enzyme. Alcohol and its breakdown product acetaldehyde also interfere with histamine breakdown. This explains why the same amount of histamine can have a stronger effect in red wine and aged cheese than on its own.

Because DAO comes from healthy gut cells, it is seen as a mirror of the gut lining. In inflammatory bowel disease Inflammatory bowel disease Umbrella term for Crohn’s disease and ulcerative colitis: long-term, relapsing inflammation of the gut that needs medical treatment. More in the chapter “Immune system and inflammation” and during chemotherapy it falls, and the more damaged the lining, the lower it gets. Some DAO also reaches the blood. But this blood value does not mirror one to one how much DAO is working in the gut. It also depends on release, breakdown and the measuring method, and varies strongly between single measurements.

A side glance at pregnancy is interesting: the placenta makes large amounts of DAO, and the level in the blood rises markedly. This is regarded as an explanation for why some women with histamine intolerance feel better during this time. No treatment can be derived from it, however.

DAO activity differs from person to person anyway. What matters is not a single value but whether the whole chain of histamine load, DAO, HNMT and gut lining fits together.

Disrupted state: causes and effects

Too little DAO can have three causes: genetic (over 50 variants are known in the DAO gene AOC1, some lowering its activity), acquired through damage to the gut lining, or temporary through inhibiting substances.

The acquired form is probably the most important. Anything that flattens the villi or damages the mature cells lowers DAO: untreated coeliac disease Coeliac disease An autoimmune disease in which gluten damages the lining of the small intestine. It is diagnosed with a blood test and usually a biopsy while you are still eating gluten. More in the chapter “Lactose, fructose, gluten: making sense of intolerances”, inflammatory bowel disease, infections, chemotherapy, alcohol, surgery and small intestinal bacterial overgrowth Small intestinal bacterial overgrowth (SIBO) Too many bacteria in the small intestine, where normally few live. Bloating and diarrhoea are typical; it is usually diagnosed with a breath test. More in the chapter “When the small intestine is too densely colonised”. When the lining heals, DAO often rises again. For this reason, a low DAO value is more a hint of a lining problem than a disease of its own.

Medicines: in the lab, chloroquine and clavulanic acid, which is in amoxicillin combinations, inhibit DAO by over 90 %, and verapamil and cimetidine clearly too. Weaker inhibition was seen with metamizole, diclofenac, acetylcysteine, amitriptyline, metoclopramide, clonidine and cefuroxime, among others. An estimated 20 % of people in Europe regularly take such drugs. Whether the inhibition matters in the body is mostly unstudied.

When the small intestinal lining is damaged, DAO and lactase often fall together, for example after gut infections, in untreated coeliac disease or after bowel surgery. If you suddenly tolerate milk and aged foods worse, you may not have two problems but an irritated gut lining.

Beware of quick conclusions: vitamin C is often recommended against histamine. In lab experiments, however, vitamin C itself is on the list of substances that inhibit DAO, as is vitamin B1. But such measurements are prone to interference: they track how much hydrogen peroxide is formed as histamine is broken down, and vitamin C and other reducing agents consume exactly that hydrogen peroxide. A low reading therefore does not necessarily mean the enzyme is inhibited. Solid studies in humans are lacking either way.

Equally important: a low DAO does not automatically explain symptoms. Many people with low values have no symptoms, and the other way round. DAO is one possible building block, not the whole answer. HNMT, mast cells Mast cells Immune cells beneath the skin and mucous membranes, filled with histamine and other messengers. They raise the alarm in allergies, infections and stress. More in the chapter “Mast cells: alarm cells in the gut, histamine and the disputed MCAS” and gut bacteria play a part too.