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Functional Assessment of Urinary Neuro-biogenic Amines—A COMPREHENSIVE GUIDE

rare genetic disorders, histidine ammo-

nia-lyase deficiency or histidine decar-

boxylase deficiency, may prevent the

conversion of histidine to histamine.

These enzymatic defects may elevate

histidine levels and may result in low-

er histamine levels. Pyridoxal phosphate

(Vitamin B-6) deficiency may inhibit

histidine decarboxylase function.


histamine may result from

medications. Animal studies indicate

that morphine, clozapine, olanzapine,

methylphenidate, atomoxetine and oth-

er pharmaceuticals may increase hista-

mine release in the CNS. Increased pop-

ulations of CNS mast cells and histamine

levels have been associated with mul-

tiple sclerosis (MS). Increased levels of

histamine metabolites have been found

in the cerebrospinal fluid of schizo-

phrenic patients. Increased histamine

synthesis has been associated with stim-

ulation of dopamine, opioid and NMDA

receptors. Alterations in CNS hista-

mine levels may contribute to age-re-

lated neurodegenerative diseases such

as Parkinson’s disease and Alzheimer’s

disease. Current research indicates that

increases or decreases in CNS histamine

levels may occur locally in specific brain

areas during neurodegenerative diseases.

Patients with allergies or mastocyto-

sis may have higher plasma histamine

levels. Certain bacteria in the gastro-

intestinal microbiome may synthesize

histamine, and some patients with gas-

tric carcinoid tumors may have elevat-

ed histamine levels. Elevated plasma

histamine and diamine oxidase (DAO)

deficiency have been associated with in-

flammatory bowel disease (IBD), aller-

gic enteropathy, colorectal cancers, and

food allergy. DAO is a copper-binding


Synthesis and Metabolism:











Histamine is synthesized by immune

cells, platelets, histamine neurons, and

gastrointestinal enterochromaffin cells.

Histidine is converted into histamine

by histidine decarboxylase, which re-

quires a pyridoxal phosphate (vitamin

B6) cofactor. Deficient function of hista-

mine decarboxylase has been associated

with symptoms of Tourette’s syndrome.

Histamine is stored in neuron vesicles

until released. Histamine synthesis may

be influenced by oxidative stress, gluco-

corticoids, gastrin and other neuroac-

tive peptides. Histamine is inactivated

in the synapse by extracellular hista-

mine N-methyltransferase (HNMT).

HNMT requires S-adenosyl methionine

(SAM) as a methyl donor. Diamine ox-

idase (DAO) degrades histamine, and

one of its metabolite is neuro-active.

Monoamine oxidase B (MAO-B) may

further degrade histamine metabolites.

Approximately one percent of the

population has histamine intolerance,

caused by reduced diamine oxidase

(DAO) activity. DAO degrades ingested

histamine, and may scavenge extracel-

lular histamine in the body. Symptoms

of DAO deficiency may resemble al-

lergic hypersensitivity reactions, but

are caused by the ingestion of hista-