Many Effects of Histamine Neurotransmitter

Jessica Pizano, MS, CNS

Many Effects of Histamine Neurotransmitter

For the vast majority of practitioners, histamine is only relevant when considering immune responses to environmental insults, especially during certain seasons. However, its functions in the body are both numerous and far reaching as it is also a neurotransmitter.

Histamine is released in the body upon mast cell degranulation and may be received by one of four receptors (H1R-H4R). Of these receptors we primarily understand the H1R (found throughout the body in smooth muscle, vascular endothelial cells, heart, and central nervous system) and the H2R (triggers gastric secretion of histamine to regulate HCL production). Pharmacologically, H1 antagonists are antihistamines. H2 blockers are medications traditionally prescribed for those with acid reflux.

Individuals can have varying levels of tolerance to histamine. Those with lower tolerance or mast cell activation may have elevations in measurable histamine. The shorthand for such individuals may be HIT or MCAD. HIT may occur when there are single nucleotide polymorphisms (SNPs) influencing the enzymes diamine oxidase (DAO) and amiloride binding protein 1 (ABP1). Ingestion of foods that are high in histamine including alcohol, fermented foods, mature cheeses, smoked foods, shellfish, beans, nuts, chocolate, vinegar, wheat, tomatoes, and citrus may be a challenge for those who have lower histamine tolerance.2 Interestingly, elevated histamine levels also inhibit DAO. Situations arise when there are either an increased numbers of mast cells or there are normal numbers of mast cells that degranulate frequently. Typical testing will include serum total tryptase (above 20 ng/mL is abnormal), urinary N-methylhistamine, plasma histamine, and bone biopsy (to look for elevated mast cell counts). Additional markers include elevated chromogranin A, plasma heparin, leukotrienes (B4, C4, D4, E4), PGD2, or its metabolite 11-β-PGDTα. Molderings and co-authors published a primer for mast cell activation for clinicians and scientists in 2011.3

Histamine, in its role as a neurotransmitter, works to control the sleep-wake cycle. It may decrease GABA levels and increase norepinephrine and epinephrine levels. Histamine may cause increased permeability of the blood-brain barrier. It also significantly influences neuroendocrine control including behavioral state, biological rhythms, energy metabolism, thermoregulation, fluid balance, stress, and reproduction. Elevated histamine may affect thyroid function. Histamine may play a role in neurocognitive function as well.1

Appropriate methylation is also essential for proper histamine catabolism. Histamine N-methyltransferase (HNMT) is an enzyme required for breakdown of histamine in the intracellular pathway. Any enzyme that has the name “methyltransferase” requires a methyl donor to function. In this way, decreased methylation may also cause increased histamine levels. Further, immune factors may also inhibit this enzyme.4

Diagram of the histamine pathway

The extracellular histamine pathway is used to degrade histamine in the gut whereas the intracellular histamine pathway degrades histamine in the rest of the body. Regardless of pathway, the enzyme DAO (requiring the riboflavin derived cofactor FAD is required. SNPs to DAO therefore reduce histamine tolerance. SNPs to other enzymes in the pathway or insufficiency of required cofactors may also influence histamine breakdown.

REFERENCES

  1. Haas, H. S. (2008).Physiol Rev, 1183-1241.
  2. Kohn, J. (2014).J AcadNutr Diet, 1860.
  3. Moulderings, G. B. (2011). Journal of Hematology & Oncology, 10.
  4. Nakazawa, H. S. (1994). American Journal of Respiratory and Critical Care Medicine, 1180-1185.

What to Expect When Starting an Elemental Diet

The basic premise of an elemental diet is providing nutrition in an easily absorbable form, including all macronutrie...

Read more

High Dose Probiotics: Is More Always Better?

With good gut health being at the forefront of medicine, would it be realistic to think of adding even more microorga...

Read more

Men's Health: What You're Missing

When evaluating men's health, clinicians can be myopic by primarily considering prostate health and optimizing testos...

Read more

Utilizing Adaptogens

As we continue to shift our focus on supporting the entire hypothalamic pituitary adrenal axis rather than laser focu...

Read more

The Hamilton Anxiety Rating Scale

Given that nearly everything about the science and clinical application of medicine has changed in the last sixty yea...

Read more

The New Supplement Label: What's Ahead in 2020

Starting in January 2020 the FDA will implement changes to U.S. Nutrition Facts and Supplement Facts labels, which wi...

Read more

Women and Probiotics: More Important Than You Think?

Probiotics for women and men are commonly used and shown to be efficacious in supporting a healthy digestive tract.*

Read more

How Ginger and Artichoke Work

Ginger and artichoke have been a staple of traditional medicine for centuries.

Read more

Sleep Smart: Identifying Underlying Factors

Many factors, from internal root causes to external lifestyle circumstances, can contribute to poor sleep.

Read more

Newsletter

Let’s keep in touch.