MTHFR and Histamine Intolerance: What’s the Connection?

Your genetic make-up is what makes you unique. This doesn’t mean, however, that all your genes are perfect. Genetic mutations and variations may occur. MTHFR gene mutation is one of the more common issues that people may experience. While MTHFR mutations may increase your symptoms of histamine intolerance and related symptoms, you shouldn’t be worried if you have MTHFR issues. Through natural dietary and lifestyle strategies, you can support your body and regain your health even with MTHFR mutation.

In this article, I will discuss what genes and enzymes are involved in histamine regulation. You will learn what MTHFR is and everything you need to know about MTHFR mutation. You will understand the connection between MTHFR mutation and histamine intolerance. I will explain how to get tested for MTHFR mutation. I will also offer some natural solutions for MTHFR issues and histamine intolerance. 

Genes and Enzymes Involved in Histamine Regulation

Before I jump into talking about MTHFR and its connection to histamine intolerance, I first want you to understand the genes and enzymes that are involved in histamine regulation.

  • MTHFR: Methylenetetrahydrofolate reductase (MTHFR) gene is necessary to make the MTHFR enzyme. This enzyme is necessary to convert homocysteine into methionine and plays a critical role in methylation and detoxification as well. You will learn more about MTHFR later in this article.
  • HNMT: HNMT is a gene that is needed to process, regulate, and break down histamine.
  • SAMe: S-Adenosyl-L-methionine (SAMe) is a cofactor of HNMT. It helps the formation, activation, and breakdown of a variety of hormones, proteins, and drugs in your body. Supplementing with SAMe is often beneficial for those with anxiety, depression, PMS, premenstrual dysphoria disorder, and fibromyalgia when their body is unable to naturally produce SAMe.
  • MAO: Monoamine oxidase (MAO) is an enzyme that helps the breakdown of histamine. 
  • DAO: Diamine oxidase (DAO) is an enzyme that is critical for the breakdown of histamine.

What Is MTHFR?

MTHFR is an enzyme that is the catalyst of various critical biochemical reactions that occur in your body. It is responsible for methylation, which is the process of converting vitamin B9 (folate) into methyl-folate. Methylation is important for your body for repairing damaged cells, processing hormones, detoxification, optimizing DNA cell function, regulating neurotransmitters, and metabolizing B vitamins. Clearly, MTHFR and methylation are absolutely critical for all areas of your health, including hormonal health, mental health, behavior, and sleep.

Converting homocysteine into methionine is one of the most important functions of methylation. Methionine is important for detoxification, repairing cells, building protein, processing fats, and supporting your body’s healthy inflammatory response. Methionine also produces a potent detoxifier, glutathione. Your liver breaks down methionine into SAMe, and anti-inflammatory superhero that helps to break down neurotransmitters and repair cellular damage (1, 2, 3, 4, 5, 6, 7).

What Is MTHFR Mutation?

Your MTHFR gene is one of the 20 to 25,000 genes you have in your body. It is responsible for the production of the MTHFR enzyme. 

As with any gene, genetic mutations or variations may occur. In fact, MTHFR mutations are incredibly common affecting about half of the population. They often lead to methylation issues and a variety of health issues, including histamine intolerance, allergies, hormonal issues, food and chemical sensitivities, anxiety, depression, sleep issues, and more. MTHFR genetic mutations are referred to as single nucleotide polymorphisms (SNPs). One SNP represents one single DNA building block difference. SNPs are fantastic biomarkers that can help us identify the genes that are associated with your symptoms and disease. The more MTHFR SNP mutations you have, the less effective your MTHFR enzymes will be resulting in decreased methylations and more health issues (1, 2, 3, 4, 5, 6, 7).

So how is this all related to histamine intolerance? Great question. Let’s learn more about genetic links to histamine intolerance.

MTHFR: Genetic Links to Histamine Intolerance

If you remember from earlier, HNMT is a gene that is absolutely critical for histamine processing. It also requires SAMe as a cofactor to do its job. However, SAMe requires a functioning MTHFR enzyme in order to be produced. Now you can understand that if your body is dealing with MTHFR genetic mutation, it will lead to lower MTHFR function and disrupt the HNMT’s work. This can slow the removal of histamine from your body leading to an array of symptoms associated with histamine intolerance, including anxiety, skin problems, digestive troubles, headaches, migraines, fatigue, and an abnormal menstrual cycle.

Moreover, MTHFR gene mutation also interferes with methylation. Methylation is critical for detoxification. Methylation problems may lead to your body’s inability to effectively remove toxins creating a build-up of histamine, which increases histamine intolerance and symptoms. Furthermore, mutations may occur in DAO, MAO, and HNMT as well, which can further interfere with removing histamine from your body and further increasing histamine intolerance and symptoms (1, 2, 3, 4, 5, 6, 7).

Testing for MTHFR Mutations

Your healthcare provider may be able to order an MTHFR blood test for you. However, these tests are usually not covered by insurance, can cost up to a thousand dollars, and are also less definitive and less comprehensive than cheaper alternatives.

As of right now, 23andMe test is the standard test for genetic mutations using SNP testing. While your results do not include all the genetic SNPs listed earlier, you can enter your results into a third-party company for a throughout the genetic report to determine that you have MTHFR or other genetic mutations. Be vary of the list of supplements these companies may try to sell you. Having a genetic SNP does not necessarily mean that you have a health condition. I prefer StrateGene genetic analysis from Dr. Ben Lynch for accurate results you can trust.  I recommend that you go over your results with a functional health practitioner, like myself for treatment and supplementation protocol as needed.

Solutions for MTHFR Mutations and Histamine Intolerance

If you have an MTHFR mutation and histamine intolerance, don’t worry. There are natural solutions you can try to start feeling better and live a healthy life free from symptoms.

Focus on Natural Folate

MTHFR mutations interfere with your body’s ability to methylate and convert B vitamins. I recommend that you consume natural folate and stay away from folic acid. Dark leafy vegetables are a fantastic source of folate and are low in histamine. Asparagus, broccoli, and avocados (unfortunately high in histamine) are also great options. If you are taking B vitamins, make sure to always take pre-methylated forms.

Support Your Digestive Health Issues

Digestive health issues, including leaky gut and irritable bowel syndrome, can increase histamine intolerance and its symptoms. Supporting your gut with healthy nutrition and probiotics is critical. To learn more about leaky gut syndrome and how to support your gut health, read this article.

Manage Stress

Reduce anxiety and learn to manage stress better. I recommend meditation, mindfulness exercises, journaling, breathwork, coloring, regular exercise, nature walks, yoga, qigong, TaiChi, prayer, connection with loved ones, and proper sleep.

Support Detoxification

Reduce your toxic load by eliminating toxic cleaning, body, and beauty products, and using organic, natural, and homemade alternatives. Get a HEPA filter and water purifier for fresh air and clean water. Support your detoxification pathways through hydration, exercise, infrared sauna, dry-brushing, and eating lots of low-histamine vegetables.

Elimination Diet

To address histamine intolerance,  I recommend that you follow a nutrient-dense and low-histamine diet. Remove all histamine foods for one to three months, then slowly re-introduce them one by one following The 4-Phase Histamine Reset Plan. To understand each step of this simple yet refined system, I recommend that you read my book, The 4-Phase Histamine Reset Plan: Getting to the Root of Migraines, Eczema, Vertigo, Allergies and More where I explain everything about histamine intolerance and each phase of the plan in detail. You will also find my favorite low-histamine recipes to nourish your body. 

Support Your Liver and Hormone Levels

Your liver is a major detoxifying organ that’s critical for your recovery from histamine intolerance. I recommend Optimal Reset Liver Love, a powerful blend of botanical and mushroom extracts and N-Acetyl-L-Cysteine (NAC)  for optimal liver function, detoxification, hormonal health, and brain function (8).

Reduce Histamine Intolerance

To improve histamine intolerance, I recommend HistoRelief. It is a synergistic blend of nutrients including Tinofend®, quercetin, nettle leaf, vitamin C, and bicarbonate salts, that provides natural support to balance your immune response, inflammation reduction, and histamine release (9).

Final Thoughts

MTHFR is a very common genetic mutation. While it may increase your risk of histamine intolerance and related symptoms, you can support your body with the help of natural dietary and lifestyle strategies. Follow my tips to support your body, regain your health, and live a happy life with MTHFR mutation.

If you are dealing with symptoms of histamine intolerance or suspect that you have MHTFR mutation, I invite you to schedule a consultation with us. I can help to identify the root cause of your problems and recommend a personalized treatment plan to repair your body and regain your health and well-being. Schedule your consultation here.

1. Tsaffir J. MTHFR, Methylation and Histamine in Psychiatric Conditions. Link Here
2. Lynch B. Histamine Intolerance, MTHFR and Methylation. MTHFR. Link Here
3. Matosin, N., Cruceanu, C., & Binder, E. B. (2017). Preclinical and Clinical Evidence of DNA Methylation Changes in Response to Trauma and Chronic Stress. Chronic Stress (Thousand Oaks, Calif.), Link Here
4. Reilly, R., McNulty, H, Pentieva, K, Strain, J. J., Ward, M. (2014). MTHFR 677TT genotype and disease risk: is there a modulating role for B-vitamins? The Proceedings of The Nutrition Society. 73(1):47-56. Link Here
5. Dean L. Methylenetetrahydrofolate Reductase Deficiency. 2012 Mar 8 [Updated 2016 Oct 27]. In: Pratt VM, McLeod HL, Rubinstein WS, et al., editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012. Link Here
6. Liew SC, Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet. 2015;58(1):1-10. Link Here
7. Lynch B. MTHFR Mutations and Associated Conditions. Link Here
8. Rodriguez RR. Headache and liver disease: is their relationship more apparent than real? Dig Dis Sci. 2004 Jun;49(6):1016-8. PMID: 15309894 
9. Histamine intolerance. Vickerstaff Health Services. Link Here




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.

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