Hanna Ormanczyk
effects in humans, involving tasks within the immune
and neuroendocrine systems, neurotransmission, gastric
secretion, cell life and death, and development. It is the
product of the histidine decarboxylase activity, and its effects
are mainly mediated through four different G-protein
coupled receptors. Thus, histamine-related effects
are the results of highly interconnected and tissue-specific
signaling networks. Histamine is naturally produced in
our body by mast cells or white blood cells, and it performs
different functions by binding with histamine receptors.
Depending upon their location, histamine receptors
control quite different body functions:
• Histamine H1 receptors: Smooth muscle and endothelial
cells affecting skin; blood vessels (Benadryl and
Claritin block activity of these receptors)
• Histamine H2 receptors: Cells in the intestines
control acid secretion, abdominal pain, and nausea;
heart rate (Histamine H2 receptor antagonist drugs have
been used to reduce symptoms of dyspepsia and GERD)
• Histamine H3 receptors: Central nervous system
controlling nerves, sleep, appetite and behavior
• Histamine H4 receptors: Thymus, small intestine,
spleen, colon, bone marrow and white blood cells;
immune function and inflammation
Histamine intolerance occurs when you have too much
histamine than your body is able to effectively break
down. The main enzymes in your body responsible for
breaking down histamine are diamine oxidase (DAO)
and histamine-N-methyl transferase (HNMT). The mechanism
of Histamine intolerance is proposed to be a genetic
or acquired impairment in one of these two enzymes.
DAO is produced in the intestine, so if the intestinal
function is compromised there may not be enough DAO
to degrade histamine normally. DAO activity can also be
inhibited by certain medications. Factors that contribute
to the interference of DAO and HNMT enzymes include:
Sometimes histamine levels are raised due to allergy, but
histamine intolerance is not a true allergy and it will not
show up on allergy tests. Some of the symptoms mimic a
true allergic reaction, but HIT is not mediated by IgE, so
skin testing and blood allergy tests will be negative. Histamine
intolerance appears to be more prevalent when
there is underlying gastrointestinal dysfunction such as in
inflammatory bowel disease, celiac disease, IBS, etc. Histamine
is an undercover agent for multiple rare diseases.
We often see histamine intolerance in conjunction with
leaky gut. Since intestines are where most of the DAO
enzyme is produced, body may produce less DAO when
the gut is inflamed or damaged, thus leading to a buildup
of histamine.