Histamine

Histamine is a universal stress signal, produced by virtually any cell under sufficient duress, and should be thought of as one of the primary signals of danger or damage, corresponding to the catabolic phase of an infection. 3 Peat argued that while mast cells and basophils are the usual main sources, energy deprivation activates histamine formation in all cells studied, where it functions as a basic organizing factor in immunity, promoting inflammation and coagulation. 2 He noted that histamine helps to rouse immune functions, but its effects must be blocked for the completion of immune processes; in a prolonged excess, it tends to calcify soft tissues, reducing their functions. 1 Like serotonin, it activates carbonic anhydrase, and is activated by estrogen and a reducing environment. 1

The production and effects of histamine are deeply intertwined with systemic hormonal and metabolic states. Peat identified estrogen as the main promoter of mast cell overproduction and histamine release, while progesterone and thyroid have the opposite effect, reducing histamine formation and release from mast cells. 2 He explained that estrogen activates mast cells to produce more estrogen and histamine, creating a vicious cycle, whereas increased oxidative metabolism lowers histamine and inflammation systemically, for example by lowering the ratio of estrogen to progesterone. 2 This hormonal dysregulation can cause a local uptake of water, a shift to inefficient metabolism towards lactic acid production, and a change in protein conformation that makes the cell appear antigenic, causing the immune system to attack what looks like foreign material. 5 Peat emphasized that the tissue damage from this inflammatory state is primary, and that restoring oxidative metabolism can return proteins to their natural conformation so they are no longer antigenic. 5

Histamine's role extends into chronic disease and immune dysfunction. Peat stated that mast cells and histamine are the problem that keeps the immune system from eliminating cancer, as these pro-inflammatory factors drive cancer and disrupt immune function, sometimes promoting tumor growth through specific blocking antibodies. 4 He noted that antihistamines and aspirin could produce tremendous improvement in such conditions. 4 In the context of COVID-19, Peat highlighted that the virus inactivates the ACE2 enzyme, which normally destroys the pro-inflammatory angiotensin II, making it a disease of inflammation and coagulation where histamine's role in promoting both processes is central. 2 He also connected histamine to the stress-organizing systems of the brain, noting that when anything goes wrong, the brain activates both the histamine and serotonin systems, with prolactin as one of the reacting stress hormones. 9

Several practical interventions can oppose histamine's effects. Peat pointed out that anything which energizes and restores cell function tends to prevent histamine production, specifically mentioning that coffee is a very effective signal to turn off histamine production, and that sugar definitely has the same effect. 6 He also noted that some of the shorter chain saturated fats in coconut oil have an anti-histamine effect, and that local anesthetics are functional antihistamines. 2 Peat referenced V. W. Adamkiewicz's work showing that reducing blood glucose with insulin greatly intensified allergic reactions, while increasing blood glucose prevented deadly anaphylaxis, demonstrating that energy metabolism governs the effectiveness of the immune process. 1 He dismissed the idea that histamine acts as a protective mechanism against high serotonin levels. 3