Histamine Intolerance & Genetics: Check Your 23andMe Raw Data

histamine intolerance genetics

When your body has too much histamine, it can cause symptoms known as histamine intolerance. This can be due to excess production of histamine by your body or not being able to break down histamine from foods very well.  OR… both!

Genetics plays a big role in how well your body breaks down histamine! You can use your genetic data to figure out if your genes are part of the reason why you have histamine intolerance. Knowing which genetic variants you carry leads to targeted solutions that are more likely to work for you.

Histamine Intolerance:

Classified as a biogenic amine, histamine is a molecule that plays many roles in the body. It is involved in allergic reactions, acts within our immune defense system, causes vasodilation, and is a neurotransmitter.

While most of us think of histamine only when reaching for that anti-histamine during allergy season, it is a vital part of our body’s everyday functions.

What are the symptoms of histamine intolerance?

Histamine intolerance symptoms include[ref]:

  • headaches & migraines
  • anxiety, irritability, brain fog
  • acid reflux, nausea, stomach pain
  • bloating, diarrhea, constipation
  • heart arrhythmia, dizziness
  • sinus drainage, congestion
  • hives, itching, flushing,
  • sleep problems

Most people with histamine intolerance have several of the symptoms above.[ref]

The two main causes of histamine intolerance are:

  • too little of the enzymes that are needed to break down histamine- and/or-
  • too much histamine being produced (gut microbes, mast cells degranulating, allergy).

Breaking down histamine:

Histamine is broken down by the diamine oxidase (DAO) enzyme and excreted in the intestines. So histamine that enters the body from foods or is made by the bacteria in your gut is broken down with DAO.

The histamine methyltransferase (HMNT) enzyme works throughout the body to deactivate and break down histamine created by your body.

Histamine receptors

Looking at the function of the different histamine receptors illustrates the many actions of histamine within the body.

  • H1 receptors: Smooth muscle, the endothelium (cells lining the inside of blood vessels and lymph vessels), central nervous system, and mast cells all can have H1 receptors on the surface of their cells.
  • H2 receptors: When histamine activates the H2 receptors in the stomach, acid is released. H2 receptors are also found in the intestinal tract and in the walls of blood vessels. Mast cells also have H2 receptors, which, when activated, causes the release of more histamine.
  • H3 receptors: The central nervous system and the peripheral nervous system contain H3 receptors, which act as a feedback loop for histamine levels in the CNS.
  • H4 receptors: These histamine receptors are at the core of inflammatory response.  H4 receptors are found in the bone marrow, basophils (a type of white blood cell), thymus, small intestine, spleen, colon, and mast cells. [ref]

In the intestines, which is the body’s largest immune organ, three types of histamine receptors have been found: H1, H2, and H4.  Interestingly, a study showed that people with food allergies and IBS had significantly higher levels of H1 and H2 receptors in their intestines.  [ref]

What causes mast cells to release histamine?

Mast cells are the storage site for histamine in most tissue. Allergens cause mast cells to burst (degranulate) and release histamine. Large numbers of mast cells are in the skin, bronchial tree mucosa, and intestinal mucosa. Some think that histamine intolerance is a subset of MCAS (mast cell activation syndrome).

For more in-depth info on mast cells and histamine, check out Research Studies on Mast Cells and Histamine Intolerance where I dive into all the different ways histamine can affect you.

Genetics of Histamine Intolerance:

DAO (diamine oxidase) is the enzyme produced by the intestines that breaks down histamine from foods. The AOC1 gene codes for the production of the DAO enzyme. Genetic variants in AOC1 can increase or decrease the production of the enzyme.

Note that there are rare mutations that influence DAO production not included with most genetic data, so the information below may not give you the complete picture.[ref][ref]

AOC1 (diamine oxidase):

Check your genetic data for rs10156191 (23andMe v4; AncestryDNA):

  • C/C: normal
  • C/T: reduced production of DAO, increased risk of migraines due to histamine[ref]
  • T/T: reduced production of DAO[ref], increased risk of migraines due to histamine[ref]

Check your genetic data for rs2052129 (23andMe v.5 only):

  • G/G: normal
  • G/T: reduced production of DAO, increased risk of migraines due to histamine[ref]
  • T/T: reduced production of DAO [ref], increased risk of migraines due to histamine[ref]

Check your genetic data for rs1049742 (23andMe v4 only):

  • C/C: normal
  • C/T: reduced production of DAO
  • T/T: reduced production of DAO[ref]

Check your genetic data for rs1049793 (23andMe v4; AncestryDNA):

  • C/C: normal
  • C/G: reduced production of DAO
  • G/G: reduced production of DAO [ref]

HNMT genetic variants:

Histamine n-methyltransferase is an enzyme that regulates histamine through metabolizing it from histamine into N-methylhistamine, which can then be eliminated from the body.

Check your genetic data for rs1050891 (23andMe v4, v5):

  • G/G: normal
  • A/G: reduced breakdown of histamine compared to G/G
  • A/A: reduced breakdown of histamine compared to G/G [ref]

Check your genetic data for rs11558538 (23andMe results for i3000469, v4; AncestryDNA):

  • T/T: reduced breakdown of histamine
  • C/T: reduced breakdown of histamine compared to C/C
  • C/C: normal [ref]

Methylation Cycle:
The methylation cycle plays a role in breaking down monoamine neurotransmitters including histamine.  So looking at your methylation cycle genes can also help with balancing out a histamine intolerance.

Lifehacks for histamine intolerance

Below are the research-backed solutions for histamine intolerance. You may need to try several different ‘lifehacks’ to see which works best for you.

Low histamine diet

A low histamine diet restricts the foods that contain high levels of histamine or that cause the body to release histamine.

Complete list of foods that are high in histamine 

Research studies show that a low histamine diet helps chronic urticaria (itchiness, hives), migraines, and asthma. [ref][ref]

Natural Supplements

There are DAO supplements available that may help some people who don’t produce enough of the enzyme. A recent study found that histamine intolerance symptoms improved significantly when taking DAO capsules before meals.[ref]

Pea shoots – those first few inches of the pea plant that come up in the spring –  are naturally high in the DAO enzyme.[ref] You can easily grow pea shoots at home, and they are a tasty addition to a salad.

Quercetin has also been shown in studies to inhibit mast cells from degrading. Mast cells are one way that the body releases histamine.[ref]

Gluten sensitivity

A new study looked at the correlation between symptoms of histamine intolerance and gluten intolerance.  It concluded that there was a significant overlap in symptoms and that it is possible that a low histamine diet may help people with gluten sensitivity. [ref]

Food prep to reduce histamine levels

How food is prepared makes a big difference in the histamine levels.  A recent study concluded “Frying and grilling increased histamine level in foods, whereas boiling had little influence or even decreased it. The boiling method might be helpful to control the effect of histamine in histamine-sensitive or susceptible patients, compared with frying and grilling.”

Additionally, leftovers kept in the fridge (especially meats!) can build up histamine. Instead, try putting your leftovers in the freezer and thawing them when you want to eat them.

Medications that decrease DAO

In addition to foods, drug interactions can cause a decrease in the DAO enzyme production. Metformin has been shown to decrease the DAO enzyme.

Vitamin B3 (nicotinamide or niacinamide) may increase histamine levels at doses of 100 mg or higher.[ref]

More to read

Notes about Histamine and Mast Cells

Originally published April, 2015. Updated and revised 12/2019


Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.

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