Struggling With Histamine? These Genes May be Your Problem

The role of histamine in our bodies is complex, to say the least. The endeavor to understand how genetics and nutrition influence this widely-used molecule may prove fruitful in addressing issues such as Histamine Intolerance, Mast-Cell activation syndrome (MCAS), and a myriad of other conditions.

Source: Optimus Medica


  • Histamine plays a complex role in the human body
  • Histamine intolerance (HIT) may result from many issues
  • Several key genes help regulate histamine and may play an integral role in HIT
  • Histamine genes may be blocked, inhibited, or even upregulated by certain medicines, supplements, and foods.
  • Terms like “histamine liberators” are common among histamine diets but not defined in research.


Histamine Intolerance is thought to affect as much as 1% of the global population with the majority being middle-aged persons (21). Having a general idea of histamine’s role in the body can help one better understand conditions like histamine intolerance (HIT), mast cell activation syndrome (MCAS), and possible personal risk factors.

Histamine Regulating Genes

Histamine plays a complex role in the human body. As such, the body needs some complex systems in order to fully utilize it. Among these tools are a set of genes and enzymes that help metabolize histamine, recycle it, and get rid of excess metabolites. Below are some of the more notable of these compounds.

DAO Blockers

Below is a table containing many compounds having demonstrated DAO-inhibiting activity. These compounds, some of more relevancy to modern life than others, should be realized as the decades-old data they are: 1985 to be exact. Noteworthy inclusions are Ascorbic Acid, Dopamine, Thiamine, and Acebutolol (a first-gen antihistamine).

DAO Blockers List
DAO Blockers List

HNMT Inhibitors

Diphenhydramine, a common first-gen H1 blocker (a.k.a. Benedryl) is an example of an HNMT blocker (15). This compound, along with many others, has shown significant blocking potential of the HNMT enzyme resulting in downregulated metabolism of histamine.

  • metoprine (anti-folate)
  • tacrine (anticholinergic)

HDC Inhibitors

Inhibition of the HDC enzyme would result in lower levels of histamine. This may be favorable results for those with histamine intolerance issues, allergies, or other concerns associated with high levels of histamine. Among the many compounds implicated in HDC inhibition are the following (16):

  • Catechol
  • Salicylic Acid
  • Phthalic Acid
  • Imidazole
  • L-Arginine
  • Creatine
  • Citrulline

MAOB Inhibitors

MAO inhibitors are popularized for treating health conditions such as depression, Parkinson’s Disease, PTSD, and a range of other conditions associated largely with neurotransmitters such as dopamine and serotonin.

  • Quercetin
  • Rutin
  • Catechin
  • Formononetin
  • Kushenol
  • 5-Hydroxyflavanone
  • Luteolin
  • Apigenin
  • kaempferol

High Histamine Foods & Histamine ‘Liberators’

It doesn’t take long to find low-histamine diet food lists online–there’s certainly no shortage. From the research I’ve seen, it is hard to make a case for many whole-foods that aren’t spoiled as being “high histamine.” Foods like sour kraut, sausage, cheeses, and aged beef are non-brainers. However, whole foods like vegetables and fruits aren’t as clear-cut of cases.

Final Thoughts

Histamine is a very utilized compound throughout the human body. It plays a key role in digestion, cognition, respiration, and a number of other major biological functions. Simply put, the human body would be a very different design without histamine. As with most resources that are heavily utilized, the wide range of enzymes, cofactors, and genetics involved with histamine metabolism is immense, complex, and very interconnected.


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A self-confessed health nut, student of Computer Science, SEO nut, and 3D artist. Can be found marveling at Mother Nature’s genius when away from the computer.

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