Can A MTHFR Mutation Cause Histamine Intolerance?

Category : Histamine Intolerance / MCAS

The MTHFR (methylenetetrahydrofolate reductase) gene or Mutation in the MTHFR enzyme play an interesting role for people with Histamine Intolerance. The MTHFR gene provides instructions for making an enzyme that plays a role in processing amino acids, the building blocks of proteins.(*) The MTHFR enzyme is particularly important for converting homocysteine to methionine, a step in the pathway that converts folate into its active form and ultimately helps regulate levels of various compounds in the body, including neurotransmitters and histamine.

What Does Histamine Do In The Body?

Histamine is a naturally occurring compound in the body that serves several critical functions, particularly in immune responses, gastric acid secretion, neurotransmission, regulation of blood vessels, and smooth muscle contraction. In the context of the immune system, histamine plays a pivotal role during allergic reactions.

Released by mast cells and basophils, histamine is responsible for common allergic symptoms such as itching, sneezing, runny nose, and watery eyes. It also contributes to the body’s inflammatory response by promoting swelling, redness, and increased blood flow to affected areas, aiding the healing process.

In the digestive system, histamine stimulates the production of stomach acid by acting on H2 receptors in the stomach lining. This action is vital for breaking down proteins and activating other digestive enzymes, helping support digestion. This is one of the reasons it causes bloating and is associated with many GI disorders.

As a neurotransmitter in the brain, histamine significantly influences the sleep-wake cycle, alertness, and appetite regulation, helping to maintain wakefulness during the day.

Histamine also affects blood vessels, causing them to dilate and become more permeable. This allows immune molecules and white blood cells to pass through vessel walls and reach sites of infection or injury, thereby aiding the body’s defensive actions.

Additionally, histamine induces the contraction of smooth muscles, which can influence various bodily systems, including the uterus, respiratory tract (contributing to bronchoconstriction in asthma) and the gastrointestinal tract.

When a person has histamine intolerance or MCAS, various conditions can arise. Allergic conditions such as hives, hay fever, and anaphylaxis are common manifestations. Gastric issues like peptic ulcers and GERD (gastroesophageal reflux disease) can occur due to improper regulation of stomach acid. Patients with Histamine intolerance also are at increased rates of Eosinophilic Esophagitis (EoE)

Chronic inflammation resulting from persistently elevated histamine levels can contribute to various inflammatory and autoimmune diseases.(*)

Additionally, histamine intolerance, characterized by an impaired ability to break down histamine, can lead to an accumulation of the compound, causing symptoms like headaches, flushing, hives, and as I mentioned digestive issues including SIBO. Understanding the roles and mechanisms of histamine is crucial for effectively managing conditions associated with its intolerance or dysregulation.

What Does Histamine Intolerance Have To Do With Methylation and MTHFR?

Methylation is a biochemical process that involves the transfer of a methyl group (one carbon and three hydrogen atoms) to various substrates, including DNA, proteins, and other molecules. This process is crucial for many bodily functions, including the regulation of gene expression, detoxification, and neural activity.

Histamine-N-methyltransferase (HNMT) is one of the enzymes that is responsible for the breakdown of histamine within our brain. This process of breaking down Histamine depends on adequate levels of methyl groups in the body. The methylation Cycle which involves not only MTHFR but also MTR, MTRR, and AHCY all play an important role in breaking down monoamine neurotransmitters including histamine but also in creating the methyl groups needed for the HMNT enzyme to work.

If methylation processes are inefficient due to MTHFR mutations or other (methylation genes), there may not be enough methyl groups available for HNMT to effectively break down histamine. This can result in elevated levels of histamine in the body, contributing to symptoms of histamine intolerance and conditions like MCAS.

So looking at your methylation cycle genes using a test like the Methyl Detox Profile (MTHFR, MTR, MTRR, AHCY, COMT) may also help with balancing out high histamine levels.

Get Your Methylation Cycle Genes Tested Here

MTHFR and Histamine Intolerance Depends On

1. Histamine Breakdown:

When MTHFR function is impaired due to a mutation, folate metabolism can be less efficient. This can result in decreased activity of other enzymes like histamine N-methyltransferase (HNMT), which is responsible for breaking down histamine within cells.

2. Detoxification Pathways:

MTHFR mutations can also impact the methylation cycle, which is essential for detoxification processes in the liver. Reduced capacity to detoxify can lead to an accumulation of toxins and inflammation, exacerbating histamine-related symptoms.

3. Homocysteine Levels:

An impaired MTHFR enzyme can lead to elevated homocysteine levels, which have been associated with various inflammatory conditions, potentially worsening symptoms of histamine intolerance and affecting overall gastrointestinal health.

4. Methyl groups are needed in one of the pathways of histamine metabolism.

Methyl groups play a critical role in the function of the histamine N-methyltransferase (HNMT) enzyme, which is involved in the degradation of histamine in the body. Proper functioning of the HNMT enzyme is important for managing histamine levels, and an imbalance or deficiency in this enzyme can contribute to histamine intolerance.

The methyl group used by HNMT in the methylation process is provided by S-adenosylmethionine (SAMe), a critical methyl donor in numerous biochemical reactions in the body. Without adequate levels of SAMe, the methylation process, and therefore the breakdown of histamine, can be impaired.

5. Genetic variants that affect histamine metabolism may be exacerbated by methylation cycle SNPs.

Factors that Influence HNMT Activity

1. Genetic Polymorphisms

Variations in the gene encoding for the HNMT enzyme can reduce its activity, affecting the ability to metabolize histamine efficiently. If you want to know more about the Genes involved in DAO and HNMT, I recommend you read this article, Genes involved in HNMT, DAO and histamine intolerance.

2. Availability of Methyl Groups

Adequate levels of SAMe and vitamins involved in methylation (such as B vitamins) are essential to support the methylation process carried out by HNMT.(*) Deficiencies in these nutrients can impair HNMT function. Learn how you can Improve DAO and HNMT enzymes naturally.

3. Liver Health

The health of the liver, where a significant portion of methylation occurs, also plays a role in the efficiency of histamine metabolism.

Management Histamine Intolerance When You Have MTHFR

To manage histamine intolerance, especially in individuals with MTHFR mutations, or mutations in any of the methylation SNP’s, several strategies may be considered:

1. Dietary Changes:

Following a low-histamine diet can help. This involves avoiding foods that are high in histamines and eating more foods that are low in histamine. Ensure adequate intake of nutrients involved in methylation, such as B vitamins (especially B6, B12, and folate) and methionine.

Supplement with SAMe levels is also beneficial.

2. Supplementation For Histamine Intolerance and MTHFR

Nature provides all kinds of natural antihistamine support. This can be fantastic news for people looking for natural ways to address Histamine Intolerance. Studies have shown that nature, once again provides natural remedies. Supplementing with active forms of B vitamins, especially methyl folate (5-MTHF) and methylcobalamin (B12), will help support the methylation pathways.

I recommend this supplement Methyl CPG for methylation support.

If you struggle with Histamine Intolerance (HIT) or Mast Cell Activation Syndrome (MCAS), incorporating the right probiotic supplements into your daily routine could be a game-changer. Did you know that when it comes to probiotics, some probiotic strains are considered histamine lowering, while others have the potential to raise histamine levels?

BEFORE you take a probiotic I recommend you read this article.

3. Enzyme Support:

Diamine oxidase supplements (DAO) is an enzyme that you can take that will help break down histamine in the digestive tract. It also helps break down any histamine produced by bacteria in the gut. DAO has been studied and has demonstrated its effectiveness in reducing histamine levels.

Read this article to learn more about DAO and the supplements to help with Histamine Intolerance and MCAS.

4. Medical Guidance:

Working with a Certified functional Medicine Practitioner who understands the interplay between MTHFR mutations and histamine intolerance is important. There is no cookie-cutter approach to fixing this problem. Your treatment plan is determined by the appropriate testing. If you are not testing, you’re guessing.

5. Empty Your Histamine Bucket

Finding the Root Cause of Histamine Intolerance and MCAS is not as simple as many think. Histamine intolerance has many causes and many things including certain medications can aggravate the condition.

With more and more awareness of MCAS/Histamine intolerance, doctors and patients are starting to see that it is not as rare as what was once thought. Here is where you need to know more about the potential reasons for filling up your histamine bucket. Check out this article that digs deep into the Many Root causes of Histamine intolerance and MCAS.

Here Is What You Should Remember About Histamine Intolerance and MTHFR

Managing histamine intolerance involving the MTHFR mutation requires a multifaceted approach, including dietary, supplemental, and medical interventions to ensure balanced folate metabolism and histamine regulation.
Histamine intolerance causes symptoms such as headaches and Migraines, Anxiety, Chronic Pain, Hives, Brain Fog, and heartburn due to excess histamine in the body.
MTHFR is only one enzyme in the Methylation pathway. If you were diagnosed with the MTHFR mutation, then I recommend testing for the other Genetic SNPS in the methylation pathway.
Methyl groups are needed in the HNMT pathway of histamine metabolism.
Genetic variants that affect histamine metabolism may be exacerbated by methylation cycle SNPs.
Worked with a doctor who is Experienced and Certified in Functional Medicine.

What Does Histamine Do In The Body?

What Does Histamine Intolerance Have To Do With Methylation and MTHFR?