Histamine Intolerance: Why the DAO Enzyme Story Is Incomplete, and the Real Reason Your Low Histamine Diet Stopped Working — The Bioenergetic Layer: Why Mast Cell Threshold Is the Real Variable

Beneath the four sources, the two enzymes, and the receptor layer sits the bioenergetic capacity of the entire integrated system. This is where the Host Capacity Model framework enters the histamine intolerance picture, and where the connection to chronic SIBO, MCAS, long COVID, and the broader category of host capacity limited illness becomes explicit. Mast cells maintain their resting state through active processes that require energy. The membrane stabilization that prevents inappropriate granule release, the regulatory signaling that suppresses activation in response to weak stimuli, the recycling of activated cells, and the production of the regulatory mediators that maintain immune homeostasis all require ATP. A mast cell in a bioenergetically depleted environment has a lower threshold for activation. Same trigger, larger response, slower recovery. HNMT requires SAMe. SAMe is generated through the methylation cycle, which depends on mitochondrial substrate handling for ATP and on the broader bioenergetic state of the cell for the substrate availability. A cell in a bioenergetically depleted state runs the methylation cycle inefficiently, generates less SAMe, and breaks down intracellular histamine less effectively. DAO is produced by enterocytes. The enterocyte is one of the most bioenergetically demanding cells in the body, with a complete turnover cycle every three to f