Genetics of Histamine Intolerance

Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.

What is Histamine Intolerance?

Histamine intolerance or HIT happens when the body has trouble breaking down histamine, a natural chemical found in certain foods and also made by the body. Normally, an enzyme called diamine oxidase or DAO helps remove extra histamine. But if there isn’t enough DAO or it doesn’t work properly, histamine may build up and cause problems.

Even though HIT involves histamine, a substance released in an allergic reaction, and can cause symptoms like itching, headaches, or stomach pain, it is not an allergy per se. Instead, it happens because the body can’t get rid of histamine fast enough. Many things may lead to HIT, including genetics, diet, medications, and gut health. Understanding the genetic side of HIT and how it can affect histamine breakdown is important so that professionals and doctors can find better ways to diagnose and manage HIT.

You Might Want to Read: A Quick Guide on Food Intolerances

What Causes Histamine Intolerance?

Several factors may lead to HIT, making it difficult for some people to get rid of histamine effectively. Here are some of the most common:

Genetics: Some people are born with changes in their genes that affect how their bodies produce diamine oxidase (DAO), or histamine-N-methyltransferase (HNMT), the enzymes responsible for breaking down or inactivating histamine. If someone has a genetic variants that reduce the production of these enzymes or makes them work less effectively, histamine stays in the body longer and can cause symptoms. Understanding these genetic factors helps doctors determine who may be more likely to develop HIT and find better ways to manage it.
Medicines: Certain medications, such as verapamil (used for heart conditions) and clavulanic acid (found in some antibiotics), may block DAO activity. When this happens, histamine is not broken down as quickly, leading to an overload in the body. People who take these medicines regularly may experience HIT symptoms, even if they did not have problems before. Recognizing the connection between medications and DAO function may help doctors adjust treatments to reduce histamine buildup.
Missing Nutrients: The body needs specific nutrients, like vitamin C and copper, to help DAO work properly. If someone does not get enough of these through their diet, DAO may not function well, leading to histamine accumulation. Vitamin C, for example, not only helps with DAO activity but also directly breaks down histamine. Copper is another essential nutrient for enzyme function. A lack of these nutrients may increase HIT symptoms, so making sure to get enough of them through food or supplements can be a key part of managing the condition.
Alcohol: Drinking alcohol can make HIT worse because it both increases the release of histamine and slows down its breakdown. Alcohol also blocks DAO, meaning histamine stays in the body longer. This is why some people notice symptoms like headaches, flushing, or stomach problems after drinking wine or beer, which naturally contain histamine. For those with HIT, avoiding alcohol or limiting intake can help prevent symptoms from becoming severe.
Unhealthy Gut Bacteria: The gut plays a big role in controlling histamine levels. Some types of gut bacteria produce histamine, while others help break it down. If there is an imbalance, meaning too many histamine-producing bacteria and not enough that remove it, histamine may build up, leading to HIT symptoms. Eating foods that support good gut bacteria, like fiber-rich vegetables and probiotics, may help improve HIT symptoms over time.

What are The Symptoms of Histamine Intolerance?

Since histamine affects different parts of the body, the symptoms may vary from person to person, making HIT difficult to diagnose. Here are some of the most common symptoms and how they are linked to histamine buildup:

Stomach Problems: Many people with HIT experience digestive issues like nausea, bloating, diarrhea, or stomach pain. This happens because histamine plays a role in digestion, helping the stomach produce acid. But when there is too much histamine, it may irritate the gut lining, leading to discomfort and inflammation. If a person often feels sick or has digestive troubles after eating certain foods, it could be a sign of HIT.
Skin Issues: Histamine may make the skin red, itchy, or swollen, leading to hives or rashes. This is because histamine causes blood vessels to expand, which may create inflammation under the skin. People with HIT might notice that their skin reacts to certain foods, stress, or even changes in temperature. These skin reactions can be frustrating and sometimes mistaken for allergies, but they are actually due to the body’s inability to break down histamine properly.
Breathing Problems: Some people with HIT develop a stuffy nose, sneezing, or even trouble breathing. This happens because histamine causes swelling in the nasal passages and increases mucus production. The symptoms may feel like seasonal allergies or a cold, but they are actually triggered by histamine overload. This can be especially noticeable after eating histamine-rich foods like aged cheese, wine, or fermented foods.
Heart Issues: HIT may also affect the heart and nervous system. Some people experience dizziness, headaches, or a fast heartbeat (palpitations) when histamine levels are too high. This is because histamine causes blood vessels to widen, which may lead to changes in blood pressure. If a personoften feels lightheaded or their heart races after eating certain foods, histamine buildup could be the cause.
Feeling Tired or Anxious: Histamine affects the brain, so too much of it may lead to sleep problems, extreme tiredness, or feelings of anxiety. Some people with HIT struggle to fall asleep or wake up feeling exhausted. Others may feel restless or nervous without knowing why. This is because histamine acts as a neurotransmitter in the brain, meaning it may influence mood and energy levels. If histamine is not properly broken down, it may overstimulate the nervous system and lead to these symptoms.

How Can Genetics Affect Histamine Intolerance?

Genes play a big role in how well the body breaks down histamine by coding for the proteins and enzymes that are involved. The body uses special enzymes to remove extra histamine, and these enzymes are made by certain genes. If there are changes (common variations or rare mutations) in these genes, histamine might not be broken down properly, leading to histamine intolerance (HIT). Two important genes are involved in this process:

AOC1 Gene (DAO Enzyme): This gene is responsible for making diamine oxidase (DAO), the enzyme that helps break down histamine from food. If there is a change in the AOC1 gene, the body may produce less DAO or make a weaker version of it. This means histamine from food stays in the body longer and builds up, leading to symptoms like stomach pain, headaches, and skin rashes. People with low DAO activity often struggle to eat foods high in histamine, such as aged cheese, wine, or fermented foods, without feeling sick.
HNMT Gene: This gene makes an enzyme called histamine-N-methyltransferase (HNMT), which breaks down histamine inside cells. While DAO mainly works in the gut, HNMT works throughout the body to control histamine levels. If the HNMT gene has a mutation, histamine can build up in the brain, lungs, and other tissues, leading to symptoms like anxiety, trouble sleeping, or breathing issues. Unlike DAO, which works outside of cells, HNMT helps remove histamine already inside the body.

Doctors can check for small changes in the AOC1 and HNMT genes through a process called single nucleotide polymorphism (SNP) testing. This test looks at tiny variations in DNA that might make it harder for the body to break down histamine. If someone has these genetic changes, they may be more likely to develop HIT. Understanding a person’s genetic risk can help doctors recommend better ways to manage symptoms.

How to Test for Histamine Intolerance

Since HIT symptoms can look like allergies or other food intolerances, testing is important to confirm the condition. There is no single test that can diagnose HIT, so doctors use a combination of methods to assess histamine levels and enzyme activity. Here are the following:

DAO Activity Test: A blood test that measures how much active DAO enzyme is in the body. Low DAO levels may mean the body cannot break down histamine properly.
Histamine Blood Test: Measures histamine levels in the blood. High histamine levels could suggest HIT, especially if DAO levels are low.
Histamine 50-Skin-Prick Test: A small amount of histamine is placed on the skin and pricked with a tiny needle. If a red, itchy bump appears and stays longer than usual, it may mean the body has trouble breaking down histamine.
Oral Histamine Challenge: The person drinks a small amount of histamine while a doctor observes for symptoms. This test can cause strong reactions and must be done under medical supervision.
Genetic Testing: Checks for genetic changes in the AOC1 gene (which makes DAO) and the HNMT gene (which helps break down histamine inside cells). This helps doctors understand if a person is more likely to have HIT due to their genetics.

Can Histamine Intolerance be Cured?

Histamine intolerance cannot be completely cured because it is often caused by genetic factors, enzyme deficiencies, or chronic conditions that affect histamine breakdown. Since the body either lacks enough active diamine oxidase (DAO) or HNMT, or has difficulty breaking down histamine efficiently for other reasons, there is no permanent fix or cure. However, it can be managed by controlling histamine levels in the body.

How to Manage Histamine Intolerance

Histamine intolerance can’t be completely cured, but it can be managed by reducing the amount of histamine in the body and improving how the body breaks it down. Here are some effective ways to manage HIT:

Eating a Low-Histamine Diet: Certain foods contain high levels of histamine or trigger its release in the body. People with HIT can reduce symptoms by avoiding aged cheese, alcohol, fermented foods, processed meats, and some fruits and vegetables like tomatoes and spinach. Fresh, unprocessed foods are usually the best choice for those managing HIT.

Taking DAO Supplements: Since many people with HIT have low levels of the DAO enzyme, taking DAO supplements before meals can help break down histamine from food. This can reduce symptoms like stomach pain, headaches, and skin reactions.

Getting Enough Nutrients: The body needs certain vitamins and minerals to help DAO work properly. Eating foods rich in vitamin C, copper, and vitamin B6 can support DAO activity and help break down histamine more effectively. Some people may need supplements if they do not get enough of these nutrients from their diet.

Keeping the Gut Healthy: A healthy gut plays an important role in histamine breakdown. Taking probiotics and eating fiber-rich foods can help balance gut bacteria, which may improve histamine digestion. Avoiding processed foods and antibiotics (unless necessary) can also support gut health.

Avoiding Certain Medications: Some drugs, such as pain relievers like aspirin and ibuprofen, some antibiotics, and blood pressure medications, can block DAO or increase histamine levels. Talking to a doctor about alternatives can help people with HIT avoid worsening symptoms.

By making these lifestyle changes, people with HIT can reduce symptoms and improve their overall well-being. While managing HIT requires some effort, understanding how histamine affects the body and taking the right steps can make a big difference in daily well-being.