Histamine that is out of balance, overwhelming the body’s ability to break it down, can cause symptoms known as histamine intolerance.
Genetics plays a big role in how well your body breaks down histamine, and you can use your genetic data to figure out if this is a reason why you have histamine intolerance.
Classified as a biogenic amine, histamine is a molecule that plays many roles in the body. It is involved in allergic reactions, plays a role in our immune defense system, acts as a vasodilator, 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.
Histamine intolerance symptoms include:
The two main causes of histamine intolerance are:
This article digs into the genes involved in the production of the enzymes that break down histamine.
Histamine is broken down and excreted by the diamine oxidase (DAO) enzyme in the gut. 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.
The other side of the histamine equation is the histamine receptors to which histamine binds.
In the intestines, which is the body’s largest immune organ, three types of histamine receptors have been found: H1, H2, and H4. Low levels of H3 were found in intestinal samples in a few of the study participants. Interestingly, those with food allergies and IBS had significantly higher levels of H1 and H2 receptors in their intestines. [ref]
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.
Genetic variants of the AOC1/ABP1 gene can affect how much DAO enzyme is produced, and HMNT variants can cause variations in the production of that enzyme also. Some of the variants that are included with 23andMe results are listed below. Note that there are rarer mutations that influence DAO production not included with 23andMe data, so the information below may not give you the complete picture.[ref][ref]
AOC1 Gene which produces DAO (diamine oxidase):
Check your genetic data for rs10156191 (23andMe v4; AncestryDNA):
Check your genetic data for rs2052129 (23andMe v.5 only):
Check your genetic data for rs1049742 (23andMe v4 only):
Check your genetic data for rs1049793(23andMe v4; AncestryDNA):
Histamine n-methyltransferase is an enzyme that regulates histamine through metabolizing it from histamine to N-methylhistamine.
Check your genetic data for rs1050891 (23andMe v4, v5):
Check your genetic data for rs11558538 (23andMe results for i3000469, v4; AncestryDNA):
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.
Most people with histamine intolerance find that a low histamine diet can help manage symptoms while getting to the root cause. There are many lists online for foods that are high in histamine or cause the release of histamine. Here is the list that I like to use.
Low histamine diet:
A low histamine diet can be difficult to incorporate at first, but it should only take a few days to a week to know if it is helping your histamine intolerance type symptoms. There are several research studies showing that a low histamine diet helps chronic urticaria (itchiness, hives), migraines, and asthma. [ref][ref]
There are DAO supplements available that may help some people who don’t produce enough of the enzyme.
Additionally, pea shoots are supposed to be naturally high in DAO.[ref] You can easily grow pea shoots at home and they are a tasty addition to a salad.
A new study looked at the correlation between symptoms of histamine intolerance and gluten intolerance. It concluded that there was significant overlap in symptoms and that it is possible that a low histamine diet may help people with gluten sensitivity. [ref]
How food is prepared makes a 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.
In addition to foods, drug interactions can cause a decrease in the DAO enzyme production. Metformin has been shown to decrease the DAO enzyme.
For anyone taking nicotinamide (also called niacinamide or B3), here is an interesting research paper looking at the increase in plasma histamine level after taking 100 mg of nicotinamide.
Read even more: Notes about Histamine and Mast Cells