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Histamine intolerance and MTHFR: How are they related?

 Histamine intolerance and MTHFR: How are they related?

 Histamine intolerance and MTHFR: How are they related?

Histamine is often associated with hay fever, hives, rashes, and other allergic reactions. These symptoms often have people googling “the best antihistamine for histamine intolerance” rather than trying to figure out what’s actually causing their reactions. 

You might be surprised to learn that histamine intolerance has been linked to the MTHFR mutation. But what’s that? 

First, let’s understand what causes histamine intolerance and your options for histamine intolerance treatment. 

What is histamine?

Histamine is a biologically active molecule known as a vasoactive amine or biogenic amine. It’s formed when the carboxyl group is removed from the amino acid histidine, a process known as decarboxylation.

These amines are chemicals which occur naturally in certain foods and are usually well-tolerated. However, some people experience symptoms after ingestion. This may be due to a lack of diamine oxidase, an enzyme that breaks down histamine in the gut. 

The highest concentrations of histamine are in the gut lining, the skin, and in the respiratory tract. Cells within these tissues called basophils and mast cells produce histamine when the body identifies a foreign substance. This can then trigger an immune response.

What is histamine intolerance?

Histamine intolerance (HIT) is thought to be caused by a disproportionate amount of histamine in the body.  [1] This accumulation is associated with an impaired ability to metabolize ingested histamine. [2]

has been linked to various physiological responses and immune reactions, including inflammation, muscle cramping, vasodilation, and the release of inflammatory chemicals. 

Histamine intolerance symptoms

Histamine is thought to cause multiple gastrointestinal symptoms, which may be accompanied by cardiovascular, respiratory and skin complaints. Symptoms of histamine intolerance may occur 30 minutes or longer after eating, although tolerance levels vary from person to person.

• Gastrointestinal: abdominal pain, diarrhea, constipation, nausea, belching, bloating

• Cardiovascular: Headache, vertigo, palpitations

• Respiratory: runny nose, nose congestion, sneezing and asthma

• Skin: Itching, rashes, redness, swelling, reddened eyelids

How is histamine made in the body?

Histamine is produced when the enzyme L-histidine decarboxylase (HDC) processes L-histidine, an amino acid required for tissue growth and repair.  

As explained above, mast cells are the major producer of histamine and express many receptors on their surface. These receptors are activated through allergens, causing the mast cells to release various inflammatory mediators including histamine.

How is histamine broken down?

Histamine is metabolized in one of two pathways. The first is in the gut by the enzyme diamine oxidase (DAO). DAO (also called histaminase) is considered the main extracellular enzyme for the intestinal degradation of histamine and other biogenic amines. Studies have shown that taking DAO supplements can help to prevent or alleviate histamine intolerance symptoms in patients. [3]

The second pathway involves the histamine N-methyltransferase enzyme (HNMT). HMNT inactivates histamine by transferring a methyl group from S-adenosyl-l-methionine (SAMe) to histamine. This process is driven by methylation. 

How does the MTHFR mutation affect histamine? 

The MTHFR gene provides the body with instructions for making methylenetetrahydrofolate reductase (the MTHFR enzyme). This enzyme converts folic acid into methylfolate, which is required for proper absorption and methylation. However, a mutation on the MTHFR gene will 

result in insufficient methylenetetrahydrofolate reductase, which means the body cannot produce the folate it needs for methylation reactions. 

Methylation plays an important role in histamine intolerance because it is required for the proper functioning of the HNMT enzyme. 

Methylation occurs as a result of two important cycles - folate and methionine. Both of these are required to produce 5-MTHF and S-adenosyl methionine (SAMe), the body’s main methyl donor. Many body systems are dependent on SAMe for this purpose.

Impaired methylation due to a MTHFR mutation can lead to low SAMe levels and COMT inhibition.[4] Reduced 5 MTHF methylation results in insufficient SAMe production for the metabolism of histamine, which can potentially lead to a buildup of histamine in the body. 

How to treat histamine intolerance if you have a MTHFR mutation

Supplements:  How methylfolate helps in histamine breakdown 

A MTHFR mutation can result in insufficient methylation and poor functioning of the HNMT enzyme. Methylation is critical for the proper function of genes involved with processing histamine and its detoxification. Proper methylation relies on specific nutrients, including the bioactive form of folate, 5-methyltetrahydrofolate (5-MTHF).

While there are no specific histamine intolerance supplements, some of the best methylfolate supplements for those with a MTHFR mutation include Methyl-Life® products such as B-Methylated II, Methylfolate 7.5+, and the Methylated Multivitamin. This range has been created by a team of natural health experts and includes the most stable, potent, and patented methylfolate. 


Eat a nutritious, low-histamine diet

If your tolerance for histamine is low, you are likely to react when you eat or drink something containing histamine.

The first step in managing your symptoms is to eat a low-histamine diet. Foods with the lowest amount of histamine are fresh, natural foods, including: [5]

• Fresh fruits and vegetables

• Gluten-free grains (these are less likely to aggravate an irritated gut lining): amaranth, corn, millet, quinoa, rice, teff.

• Fresh herbs

• Fresh animal proteins: fish, chicken, beef, lamb.

• Anti-inflammatory foods such as fatty fish, bone broth, berries

Histamine intolerance foods to avoid

The levels of histamine in foods increases with fermentation and the degree of processing. Your histamine intolerance food list might include:

• Alcohol, especially red wine

• Avocado

• Dried fruits

• Eggplant

• Processed or smoked meats: salami, sausages, pepperoni, lunch meat, hot dogs

• Fermented beverages such as kombucha

• Fermented dairy products: yogurt, kefir, sour cream, buttermilk, cottage cheese, ricotta

• Fermented vegetables: miso, kimchi, sauerkraut, pickles, natto

• Fish and seafood, especially smoked, salted, canned

• Matured cheeses

• Beans and pulses such as chickpeas, soy

• Nuts prone to mold: peanuts, cashew nuts, almonds

• Chocolates and other cocoa-based products

• Rice vinegar

• Instant or packaged meals

• Snacks and sweets with preservatives and artificial additives

• Soy sauce, tamari, coconut aminos, liquid aminos

What Does it Mean to be the “Best” Methylfolate

Manage stress and anxiety

Histamine is a neurotransmitter and has a variety of physiological roles in brain function. Acute stress increases the histamine turnover in the brain and also influences the hormones involved in the stress response. [6]

Poor gut microbiome due to gastrointestinal symptoms may also contribute to a variety of cognitive and mood disorders via the gut-brain axis. 

Effective techniques for stress management may include nutrition and exercise, along with strategies that improve cognitive and emotional functioning. Breathing meditation and yoga have been clinically proven to reduce stress and anxiety when practiced regularly.  

Support liver function 

Studies have shown that histamine levels are significantly greater in those with chronic liver disease, which suggests mast cell activation. This causes the itchy, red skin associated with histamine intolerance.

The main function of the liver is to remove toxic substances from the body. Support the liver by:

• Drinking 2-3L filtered water every day

• Exercising regularly

• Avoiding processed foods and artificial additives

• Eating an antioxidant-rich (and low histamine) diet

The takeaway

Although the MTHFR genetic mutation may increase your risk of histamine intolerance and related symptoms, it is possible to manage these symptoms through diet and lifestyle changes. Reducing your intake of histamine by eating a low-histamine diet may help to reduce symptoms. Supporting your body’s methylation process by supplementing with methylfolate will also help to break down any histamine you do ingest. Check out Methyl-Life® for the purest and most stable methylfolate currently available in the US market. 











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