Histamine Intolerance: Why the DAO Enzyme Story Is Incomplete, and the Real Reason Your Low Histamine Diet Stopped Working — Where the Standard Story Breaks Down

If the DAO deficiency model were the complete picture, several things should be true that are not. DAO supplementation should reliably resolve symptoms in patients with documented low DAO. It does not. In clinical practice, DAO supplements help a subset of patients with histamine intolerance symptoms but produce minimal effect in many others. The supplements degrade luminal histamine but do not address tissue mast cell release, do not affect intracellular histamine, do not change the gut microbial communities that may be producing histamine continuously, and do not influence the histamine receptor populations that determine what the patient feels. Low histamine diets should produce sustained improvement. They do not, in the chronic histamine intolerant patient. The standard finding is the two week plateau pattern: clear improvement in the first two weeks, plateau by week three, gradual reintroduction of reactivity to foods that were previously safe, and eventual collapse of the diet's effectiveness even with strict compliance. I have written about this pattern in detail in Why Every Protocol Stops Working After Two Weeks. Patients with severe histamine intolerance symptoms should consistently show low DAO on testing. They do not. Many patients with classic histamine intolerance presentations have normal or near normal serum DAO. The 2023 literature has noted that a substantial