TL;DR: Histamine intolerance can be linked to MTHFR gene mutations and methylation issues. MTHFR plays a key role in methylation, which supports important enzymes like HNMT that break down histamine. If you suspect histamine intolerance, trying a low-histamine diet is crucial to determine if it’s the issue. Genetic testing can reveal specific mutations that impact histamine metabolism, and personalized strategies can be developed to manage symptoms. To support healthy histamine levels naturally, focus on diet, stress management, a clean environment, and specific supplements.†
What is the Link Between MTHFR, Methylation, and Histamine Intolerance?
Histamine intolerance is becoming increasingly common, but many people don’t realize it’s often linked to MTHFR gene mutations and other methylation issues.
Dr. Ben Lynch calls the MTHFR gene your Methylation Master. That’s because MTHFR is your #1 gene in supporting SAM (or SAMe) production: essential for transferring methyl groups needed for DNA synthesis, repair, and regulating other genes.1
Here’s a breakdown of how these factors connect:
Histamine is processed by a group of enzymes. One of these enzymes, HNMT, needs SAM to do its job.2 So, for HNMT to break down histamine properly, it’s important that the MTHFR enzyme is working well to support this process.
HNMT is found throughout the body. It works by breaking down histamine that has been produced inside cells by the HDC enzyme.3
Here’s a look at some of the key enzymes involved in Histamine Metabolism:4
- HNMT – requires SAM as a cofactor.
- DAO – which requires vitamin B6 and copper.
- MAO – which requires vitamin B2 and iron.
- NAT2 – requires CoA, which stems from vitamin B5.
How to Tell if You Have Histamine Intolerance
Histamine intolerance often goes undiagnosed because its symptoms can mimic other conditions. You may be more likely to experience histamine intolerance if you have an MTHFR gene variation.5
Histamine intolerance can be understood as your body struggling to manage too much histamine, a substance it naturally uses to function.6
Think of it like trying to fit too much into a 5-gallon bucket—if you overfill it, things spill out and cause issues.
The best way to find out if you have histamine intolerance is to try a low-histamine diet for a while. If your symptoms improve, it's a strong sign that you are histamine intolerant.
Want to learn more about histamine intolerance but don’t know where to start? Download our free Histamine Intolerance Guide.
Main Genetic Factors Predisposing You to Histamine Intolerance
Certain genetic variations can predispose you to histamine intolerance, including those in the following genes:
- MTHFR: MTHFR helps regulate methylation which is needed to reduce intracellular histamine by the HNMT route.
- MAO: a gene that requires B2 as a cofactor, is slower in men and reduces tyramines, histamine, and catecholamines (stress neurotransmitters).
- DAO: a gene that requires copper as a cofactor and reduces extracellular histamine (bacteria and food).
- HNMT: a gene that requires SAMe as a cofactor and reduces intracellular histamine.
- PEMT: produces phosphatidylcholine which is needed for keeping cell membranes stable and healthy. When mast cells have robust membranes, they are more stable and release just the right amount of histamine when activated.
- COMT: helps break down estrogen and stress neurotransmitters. If both of these are high, your histamine is likely high.
To fully address each of these genes and have the best chance at balancing your histamine levels, it’s a great idea to read Dirty Genes.
Just taking supplements or medications probably won’t help your histamine intolerance if you're not making the necessary adjustments to support your overall health. Supplements are meant to enhance, not replace, healthy habits like good nutrition and a balanced lifestyle.
As you improve your diet, lifestyle, environment, and mindset, many issues may start to resolve on their own—though this isn’t always the case. Remember, supplementation works best when all systems are supported.
How to Identify if Your Histamine-Related Genes Are Affected by Mutations
Genetic testing offers a unique opportunity to uncover valuable insights about your health. Like any decision, it comes with its own set of benefits and drawbacks.
Genetic Testing is for you if:
- You want to identify which specific supplements and lifestyle strategies are most effective for you.
- You have been struggling with chronic health issues, and current approaches haven’t provided any relief.
- You are comfortable with the financial investment required for genetic testing.
- You are curious about your genetics and deeply interested in exploring this area.
Here are the companies that Dr. Lynch recommends for Genetic Testing:
- SelfDecode: this company is privately owned and operated. The owner, Joe Cohen, is passionate about educating people about genetic variations. Use code SDDRLYNCH to save 10% on your purchase.
- Ancestry: you can get this on Amazon, and it’s quite inexpensive and fast.
Once you have your genetic data, you can upload it to the Histamine Genetic Report, which helps you understand your genetic vulnerabilities to histamine and provides strategies to support your histamine pathway genes with lifestyle, food, environment factors, and nutrients.†
Easy Ways to Manage and Support Histamine Levels
Can you “cure” histamine intolerance?
No.
Can you maintain and support your body’s ability to balance histamine levels?
Absolutely.
Here are some simple ways you can get started:
- Diet: Focus on fresh, unprocessed foods. Avoid fermented foods, leftovers, citrus, alcohol, and aged items like cheese, wine, and processed meats. Stick to fresh fish or skip it entirely. Limit protein intake to roughly 0.8 grams per 2.2 lbs of body weight since excess protein can convert to histamine. Incorporate healthy fats like ghee and whole grains such as quinoa or wild rice.
- Lifestyle: Prioritize sleep and stress reduction, as these are crucial. Practice breathing techniques, exercise appropriately without overexerting yourself, laugh often, and engage in activities you genuinely enjoy—don’t put them off.
- Environment: Create a clean, allergen-free space. Use a new pillow with dust mite covers, clean your house and air ducts, invest in air purifiers, and filter your water. Avoid air fresheners, as they can worsen histamine intolerance. Replace carpets with hardwood or tile flooring if possible, ensure good airflow with fresh air circulation, and use air recycling in your car when stuck in traffic.
- Mindset: Cultivate a positive mindset and take a proactive attitude toward your own well-being. Move away from a "fix me" mentality and understand that taking responsibility is key. Seek out healthcare providers who understand histamine intolerance, MTHFR, and methylation.
- Learn: Expand your understanding by reading resources like Dirty Genes and The Histamine Workbook.
- Supplements: When needed, consider supplements specifically designed to support histamine intolerance.†
Histamine Intolerance Supplements by Seeking Health™
Histamine Digest supports your DAO enzyme directly by providing you with the DAO enzyme right in the capsule. The patented DAOgest® enzyme supports healthy histamine levels in the small intestines, colon, uterus, bladder, prostate, placenta, and breast milk.
Histamine Nutrients provide nutrients and bioactive compounds needed to support healthy histamine breakdown throughout the whole body. Each nutrient included is directly associated with the genes that break down histamine.
ProBiota HistaminX is a histamine-friendly probiotic specially formulated to exclude strains known for high histamine production. Supports a balanced microbiome and promotes a healthy gut response to dietary histamine.
HistaminX supports healthy mast cell stability and inflammatory responses, promoting immune health and comfort during the changing seasons. This helps keep histamine inside your cell vs getting out into the blood. Do not use if pregnant.
Glutathione Plus Lozenge helps support histamine intolerance through its antioxidant properties, support for immune function and methylation, enhancement of histamine metabolism, and promotion of enzyme activity necessary for breaking down histamine.
Liposomal Vitamin C supports cell membrane stability, thereby reducing the release of histamine, while also supporting healthy inflammation levels related to mast cell activation.
Fish Oil assists with mast cell stability, thereby reducing the unnecessary release of histamine. This is achieved by serving as essential building blocks for membranes and supporting healthy levels of inflammation.
Comprehensive Histamine Support†
Histamine Bundle: This provides you with the top 4 best-selling histamine-supportive supplements at a 20% savings:
- ProBiota HistaminX
- HistaminX
- Histamine Digest
- Histamine Nutrients.
- Bonus: The Histamine Workbook (free). The workbook points you to the potential causes of high histamine in your life. There are many, and there are some odd ones. Then, it guides you on how to eliminate each contributing factor so your histamine intolerance improves bit by bit. It’s all about total load. The more factors you identify and remove, the better you feel.
Histamine Genetic Report: The most comprehensive tool to help you identify and support your genetic vulnerabilities to histamine. Use your genetic raw data from 23andme, Ancestry, and SelfDecode.
The Bottom Line
Histamine Intolerance is sometimes linked to MTHFR variations and methylation issues, and the main genetic factors that predispose you to it are MTHFR and other key genes like MAO, DAO, and HNMT. Supporting your MTHFR gene by avoiding folic acid and prioritizing proper methylation can significantly help. To take control of your histamine symptoms, consider genetic testing, but mainly focus on optimizing your diet, lifestyle, environment, and mindset as part of a holistic approach.
References:
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8703276/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC6386932/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC6386932/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7463562/
- https://pubmed.ncbi.nlm.nih.gov/25449138/
- https://pubmed.ncbi.nlm.nih.gov/17490952/
† These statements have not been evaluated by the Food and Drug Administration (FDA). This product is not intended to diagnose, treat, cure, or prevent any disease.