inflammation & autoimmunity

AOC1

How to Combat Histamine Intolerance Through Genetics (DAO)

Written by Jasmine Foster, BSc, BEd on September 9th, 2019

Do you get migraines or rashes after eating certain foods? Your genes affect how well two important enzymes clear histamine from your gut, skin, and brain. We’ll explore your genetic risk of intolerance and how to combat it.

What is Histamine Intolerance?

People with histamine intolerance have too much histamine: they either create it in excess or they can’t break it down quickly enough [R].

As a result, when they eat foods that contain histamine, it crosses into their blood, and they experience inflammation; by contrast, a healthy person would break down most dietary histamine before it ever reaches the bloodstream [R, R].

The most common culprit is low diamine oxidase (DAO), the enzyme that breaks histamine down in the gut [R].

Allergy-Like Symptoms

Histamine intolerance mimics an allergic reaction. Symptoms may include diarrhea, headaches, stuffy and runny nose, eye redness, asthma, low blood pressure, arrhythmia, hives, itching, and flushing [R].

People with less efficient DAO are more likely to suffer from migraine headaches as well. According to one study, those with the ‘T’ allele at rs10156191 or rs2052129 (or both) are at a significantly higher risk of developing migraines [R].

How Can You Tell If You’re Intolerant?

Approximately 1% of the population has histamine intolerance. In contrast to food allergies, in which even a small amount of the allergen causes a reaction, the cumulative amount of histamine is crucial to inducing a reaction [R].

Although 75 mg of liquid histamine can provoke symptoms in healthy volunteers, defining the safe threshold level in sensitive individuals is difficult. Canned sardines, which are very likely to trigger symptoms in intolerant people, have as much as 20 mg per 100 g, but some people react to foods that contain much less [R, R, R, R].

If you think you may be intolerant, monitor yourself for allergy-like symptoms after you consume a high-histamine food such as canned sardines.

Histamine intolerance, which is most often caused by deficient or defective DAO enzymes, causes allergy-like symptoms including headaches, rashes, and a stuffy nose.

Why is AOC1 (DAO) Important?

AOC1 (or DAO) codes for diamine oxidase, one of the major enzymes that breaks down histamine. DAO is mostly found in the gut, though it’s also in the kidneys and connective tissues [R, R].

Because of its location in the gut, this enzyme is our primary defense against histamine and histamine-producing bacteria in our food. Unsurprisingly, DAO deficiency is the primary cause of histamine intolerance [R].

DAO is the major histamine-degrading enzyme in the gut. It is our primary defense against histamine produced by bacteria in our food.

Your Histamine Gene Results for Intolerance Risk

Important SNPs

AOC1 rs10156191:

‘C’ = Normal production of diamine oxidase (DAO)
‘T’ = Reduced production of DAO, increased risk of histamine intolerance

AOC1 rs2052129:

‘G’ = Normal production of DAO
‘T’ = Reduced production of DAO, increased risk of histamine intolerance

AOC1 rs1049742:

‘C’ = Normal production of DAO
‘T’ = Reduced production of DAO, increased risk of histamine intolerance

AOC1 rs1049793:

‘C’ = Normal DAO enzyme activity
‘G’ = Reduced DAO enzyme activity, increased risk of histamine intolerance

SNP Table

variant	genotype	frequency	risk allele
rs10156191
rs2052129
rs1049742
rs1049793

How Does Defective DAO Cause Problems?

Defective or deficient DAO is the leading cause of histamine intolerance. Any one of several variations (as shown in the table above) can slow down your DAO enzyme; the more bad variants you have, the more likely you are to be intolerant [R, R, R].

Recommendations

To Prevent Histamine Release

Most of the strategies for managing histamine intolerance prevent histamine from being either produced (histidine decarboxylase inhibitors) or released (mast cell stabilizers). Over on SelfHacked, we’ve compiled a comprehensive list of supplements and lifestyle options that can help; check out this post to see them all.

It’s also a good idea to reduce the amount of histamine you consume in your food. This post explains how to make the most of a low-histamine diet. For a dive into which foods are high and low in histamine, check out this post.

To Increase DAO Activity

Diet

Lathyrus sativus (white pea or grass pea) is a tropical legume that naturally contains DAO. However, it also contains a neurotoxin that can be dangerous if the peas are not properly prepared. If you choose to eat white peas, make sure to closely follow cooking instructions to eliminate the threat [R, R].

DAO requires vitamin C, vitamin B6, and copper to function normally. Make sure you get enough of these nutrients in your diet [R].

The omega-3 fatty acids DHA and EPA appear to encourage the release of DAO in the gut. These healthy fats are generally anti-inflammatory, so it’s a good idea to increase your intake [R, R].

Supplements

The simplest solution for reduced DAO activity is also the easiest: diamine oxidase is available as a supplement. DAO supplements reduce or eliminate headaches in people with confirmed enzyme deficiency [R].

You can also get DHA and EPA as a supplement by taking fish oil [R].

Drugs

Diphenhydramine (the active ingredient in Benadryl) blocks histamine from binding to the H1R receptor, but it may also increase DAO activity. In one cell study, diphenhydramine enhanced DAO by 19% at the highest studied concentration. Note, however, that this effect has not yet been observed in animals or humans [R].

Jasmine Foster

BSc, BEd

Jasmine received her BS from McGill University and her BEd from Vancouver Island University.

Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

More inflammation & autoimmunity blogs

How to Combat Histamine Intolerance Through Genetics (DAO) Are You Genetically Vulnerable to High Brain Histamine, Migraines, or ADHD? (HNMT) How to Tell if You’re Lectin Sensitive Using Your Genetic Data (CNR1) Are You Sensitive to Lectins? (MTHFR) Fight Oxidative Stress, Inflammation, and Brain Fog (PARP1) Is This Gene Causing Your Autoimmune Problems? (PTPN22) Are You Genetically Susceptible to Post-Treatment Lyme? (ABCB1) A Key Genetic Player in Autoimmunity (HLA-B) Is This Inflammation Gene Reducing Your Intelligence? (TNFSF9) Can You Manage Allergies and Asthma by Balancing Methylation? (MTHFR)

Content

What is Histamine Intolerance? Your Histamine Gene Results for Intolerance Risk How Does Defective DAO Cause Problems?

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