Histamine Intolerance: Why the DAO Enzyme Story Is Incomplete, and the Real Reason Your Low Histamine Diet Stopped Working — What the Standard Story Says About Histamine Intolerance

The standard story, which is what you will find on virtually every patient facing website and in most functional medicine resources, runs as follows. Histamine is a biogenic amine that the body produces and that is also present in food, particularly fermented and aged foods (cheese, wine, cured meat, sauerkraut, kombucha, soy sauce, fish sauce, leftovers). Histamine performs many functions in the body, including immune signaling, gastric acid secretion, and neurotransmission. Mast cells are the principal source of endogenous histamine in tissue. When histamine accumulates beyond the body's capacity to clear it, symptoms appear: flushing, hives, itching, headache, brain fog, anxiety, nasal congestion, gastrointestinal symptoms, palpitations, and others. The body has an enzyme called diamine oxidase (DAO) that breaks down histamine in the gut, before it can be absorbed into the bloodstream. DAO requires several cofactors to function: vitamin B6, copper, and vitamin C. Some people have lower DAO activity, either because of genetic variants in the AOC1 gene that encodes DAO, because of gut conditions that reduce DAO production, because of medications that block DAO, or because the cofactors are insufficient. When DAO is low and dietary histamine is high, histamine accumulates and the patient develops symptoms. The standard treatment plan follows from the standard story. Reduce diet