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Exploring the Role of Genetics in Histamine Intolerance and Symptom Expression

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Uncovering Six Key Genes Behind Histamine Intolerance

Histamine intolerance, with its array of frustrating symptoms, confuses many individuals seeking relief. But here’s the thing: our genetics play a big role in how our body metabolizes histamine. 

Yes, you read that right – our very own genes play a role in determining our susceptibility to histamine intolerance. And I’ve experienced this first hand. 

You see, I happen to have the MTHFR gene mutation – a genetic quirk that affects how my body handles folate, a crucial nutrient. But little did I know that this seemingly innocent mutation would have a surprising impact on my histamine intolerance journey!

So let’s uncover how genetics influence histamine metabolism and regulation and reveal how six common gene variations can sway the intensity and expression of symptoms.

Is Histamine Intolerance Genetic?

The short answer is yes. Genetic factors can influence your susceptibility to developing histamine intolerance. 

Specific histamine metabolism and regulation genes have been associated with an increased risk of histamine intolerance. And variations or mutations in these genes can affect the production or activity of enzymes responsible for breaking down histamine or the sensitivity of histamine receptors in the body. 

However, your genetic predisposition alone is not the sole determinant of histamine intolerance. Other factors, such as diet, environmental triggers, and overall health, can also contribute to the development and manifestation of histamine intolerance symptoms. 

How do genetics influence histamine intolerance symptoms?

histamine genetics

Genetic factors can impact histamine intolerance by influencing diverse elements of histamine metabolism and regulation within the body. The following are several ways in which genes can determine an individual’s vulnerability to histamine intolerance:

  • Enzyme Activity: Genes play a role in producing enzymes involved in histamine metabolism. Variations or mutations in genes, such as DAO, can lead to reduced enzyme activity, resulting in impaired histamine breakdown and an increased risk of histamine intolerance. 
  • Enzyme Regulation: Genes can also influence the regulation of histamine-metabolizing enzymes. Variations in genes such as HNMT or HDC can affect the activity and expression of these enzymes, impacting the production and breakdown of histamine.
  • Histamine Receptors: Genes coding for histamine receptors, such as the HRH1 gene, can influence the sensitivity and response to histamine. Genetic variations in these receptors may affect how your body’s cells and tissues react to histamine, potentially contributing to the development of histamine intolerance symptoms.
  • Genetic Interactions: Histamine intolerance is likely influenced by the interplay of multiple genes rather than a single gene alone. Different genetic variations can interact with each other or with other factors, controlling your histamine intolerance’s overall risk and severity.

Understanding the genetic aspects of histamine intolerance provides valuable information that allows for a comprehensive approach to managing the condition. Integrating genetic insights with dietary modifications, environmental awareness, and overall health considerations enable me to provide personalized strategies that will help you effectively manage histamine intolerance and mitigate your symptoms.

Six Common Genes That Affect Histamine Intolerance

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Several genes have been identified as potentially influencing histamine intolerance. Six of the most common genes associated with histamine intolerance include: 

1. DAO

The DAO gene plays a crucial role in producing the enzyme diamine oxidase (DAO), which breaks down histamine in the digestive tract. 

DAO typically metabolizes histamine from ingested food or produced by the body to prevent its accumulation and the onset of symptoms. Variations or mutations in the DAO gene can affect the production or activity of the DAO enzyme, leading to impaired histamine breakdown, which causes histamine to accumulate in the body and potentially trigger histamine intolerance symptoms.  

People with DAO gene variations may experience headaches, migraines, digestive issues, skin problems, and allergic-like reactions after consuming foods high in histamine or histamine-releasing substances.


The HNMT gene codes for the enzyme histamine N-methyltransferase (HNMT), which plays a role in the breakdown and inactivation of histamine in the body.

Variations or mutations in the HNMT gene can impact the activity or expression of the HNMT enzyme, affecting the efficiency of histamine metabolism. This leads to reduced histamine breakdown and increased histamine levels in the body.

People with HNMT gene variations may experience symptoms of histamine intolerance, such as headaches, nasal congestion, skin rashes, GI issues, and other allergic-like reactions. 

3. Histidine decarboxylase (HDC)

The HDC gene, which stands for histidine decarboxylase, plays a crucial role in the production of histamine within the body. 

The HDC gene provides instructions for producing the histidine decarboxylase enzyme, which converts the amino acid histidine into histamine. Variations or mutations in the HDC gene can impact the histidine decarboxylase enzyme’s activity or expression, leading to changes in histamine production. This can result in imbalanced histamine levels, contributing to histamine intolerance symptoms.

When the HDC gene is affected, it can increase or decrease histamine production depending on the specific variation. Higher histamine synthesis can result in an excess of histamine in the body, leading to heightened sensitivity and intolerance symptoms. On the other hand, lower histamine synthesis may affect the body’s ability to maintain optimal histamine levels, contributing to histamine intolerance symptoms.


The MTHFR gene, which stands for methylenetetrahydrofolate reductase, is not directly linked to histamine intolerance. However, it plays a crucial role in a biochemical process known as methylation. The MTHFR gene provides instructions for producing the MTHFR enzyme, which converts folate (vitamin B9) into its active form called methylfolate. Methylfolate is a critical component in the methylation process, which affects various bodily functions, including the metabolism and elimination of histamine. 

Impairments in the MTHFR gene can result in decreased production or activity of the MTHFR enzyme, leading to reduced methylation capacity. This can affect the body’s ability to regulate histamine levels and may contribute to histamine intolerance symptoms. In addition, individuals with MTHFR gene variations may also have a higher tendency to have imbalances in other methylation-related processes, which can further impact histamine metabolism and intolerance.

So while the connection between the MTHFR gene and histamine intolerance is not direct, it highlights the importance of considering overall methylation capacity in relation to histamine regulation.

5. HRH1

The HRH1 gene plays a role in determining the sensitivity and responses to histamine by encoding the H1 receptor (proteins found on the surface of cells that bind to histamine and mediate its effects). 

Altered HRH1 gene variants can lead to increased sensitivity or overactivation of the H1 receptor, causing exaggerated responses to histamine. This heightened sensitivity can contribute to the manifestation of histamine intolerance symptoms, such as skin rashes, itching, nasal congestion, and respiratory difficulties.

Some individuals may have HRH1 genetic variants that result in reduced sensitivity or impaired function of the H1 receptor. In such cases, the body may have difficulty responding appropriately to histamine, potentially leading to histamine accumulation and intolerance symptoms.

6. MAO

The primary role of the Monoamine Oxidase (MAO) enzyme is to degrade biogenic amines like tyramine and catecholamines. Still, it can also impact histamine levels in the body. 

When there is insufficient MAO or a change in the gene responsible for its production, histamine levels may be affected. Lower levels of MAO can result in reduced breakdown of histamine, leading to high histamine concentrations in the body. This imbalance can contribute to the development or exacerbation of histamine intolerance symptoms.

Additionally, variations in the gene that controls the production of MAO can also cause fluctuations in the levels of other biogenic amines. When these levels rise alongside histamine, the overall impact on symptoms can be more severe.

Genes Aren’t Everything

Even though these genes have been implicated in histamine intolerance, the understanding of this condition is still evolving, and individual genetic variations may interact with other factors to determine your susceptibility to histamine intolerance.

Remember, genes aren’t everything when it comes to histamine intolerance. 

While genetics certainly plays a role, numerous other factors, such as dietary triggers, gut health, hormone balance, environmental allergens, stress levels, underlying medical conditions, medication usage, lifestyle choices, and overall well-being, can affect histamine intolerance. A comprehensive approach that considers all of these factors is important for effectively managing the condition. 

If you suspect histamine intolerance, I encourage you to talk with your care to understand your genetic profile better profile and receive individualized guidance in managing histamine intolerance effectively.  

Get Started On Your Journey to Wellness

It’s never too late to get started on your journey to wellness! And I’m living proof of that!

I was in my 30s and a practicing functional medicine provider before I began piecing together my histamine intolerance issues. But when I realized that my symptoms and food sensitivities were driven by histamine intolerance, I started following the plan outlined in my book and online programs. And now, I can eat most foods without any problems, most of my symptoms are gone, and I live a pretty normal life. 

And now it is your turn!

Learn how histamines impact your health and access my simple 4-step plan for overcoming your histamine intolerance with the Histamine Reset Online Program.

It’s time to change and take control of your health! Get started on your wellness journey today!



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Hi, I am Dr. Becky Campbell. I work with men and women who’ve had a health set back and are willing to do whatever it takes to reach optimal health so they can perform their best in their careers and be fully present with their family again.