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High Histamine, gene SNPs, and MTHFR

Histamine and MTHFR are bound together for so many reasons. One, is because just like MTHFR, histamine has its fingers in so much more than just allergies.

Histamine is involved in:

  • Allergic reactions – this is the part everyone knows about.
  • Immune response
  • Opening blood vessels (or vasodilation)
  • It’s a neurotransmitter!
  • Signaling within your stomach

Histamine levels in your body depend on two factors.

  1. How much histamine is being produced – this depends on your gut microbiome, how easily your mast cells degranulate, and allergies and the action of your basophils, which are one of your white blood cells.
  2. How much histamine is being broken down – this depends on MTHFR, and two histmine-specific enzymes called DAO and HNMT.

Histamine is mostly formed in your mast cells, which are immune cells that protect sites vulnerable to injuries like mucus membranes in your nose and mouth, your internal body surfaces, and the insides of your blood vessels. Also, in your basophils, which are white blood cells in your immune system that respond to allergins. It is also scattered throughout your body tissues and has an incredibly diverse range of effects including:

  • Promoting wakefulness (otherwise known as stopping a good night’s sleep)
  • Constricting airways
  • Increasing stomach acid secretion
  • Modulating pain signals
  • Itch perception
High histamine symptoms, histamine and MTHFR, histamine and natural remedies,

Histamine is important with MTHFR for a couple of other reasons as well. Histamine breakdown is dependent on healthy methylation just like other monoamine neurotransmitters, and the HNMT enzyme needs a methyl group from SAMe in order to function. That means if you have a sluggish MTHFR, then it is much harder to break down histamine and you are more likely to have a high histamine picture.

Keep in mind that high histamine states are one of the characteristics of the “undermethylation” (legacy term) basic state – these are the folks I like to call the Achievers. Of course more than just your MTHFR status goes into high histamine – there are several gene SNPs that can affect it including DAO and HNMT – the two major histamine breakdown pathways – but it is still really useful for us MTHFR folks to know. I believe this simply because the general patterns between over- and under-methylators (again, that’s a legacy term handed down from the Walsh Research Institute and doesn’t necessarily describe what is happening physiologically) are still really useful.

The most useful aspect, in my opinion, is the drug and supplement reactions in each group, which I find to be shockingly accurate.

Gene SNPs That Affect HIstamine

  1. MTHFR and other genes in the methylation pathway – especially MTR (or MTRR which affects MTR’s ability to function. Remember that MTHFR is dependent on riboflavin as well, so low riboflavin status can look like difficult methylation.
  2. DAO – DAO is one of the major breakdown pathways of histamine and gene SNPs can cause problems.
  3. HNMT – HNMT is the other major breakdown pathway and it needs a SAMe (from the methylation cycle) in order to function.

High Histamine Symptoms Include

  • Seasonal allergies that present as hayfever type allergies – sneezing, watery eyes and runny nose, itching, hives, itchy nose, sudden symptoms.
  • Headaches and migraines
  • Shortness of breath
  • Skin itching for no apparent reason, or because of any and everything that happens, and low pain tolerance
  • Digestive symptoms including cramping, diarrhea, and bloating
  • Wakefuless, insomnia, anxiety
  • Drop in blood pressure, dizziness on change of position, or irregular heart beat.

Managing High Histamine Naturally

HIgh histamine can be seasonal, or it can be constant in the case of something called Histamine Intolerance. Either way, here are some steps you can take toward managing high histamine levels.

 Having high histamine levels, genes with SNPs, and MTHFR mutations
Having high histamine levels, genes with SNPs, and MTHFR mutations
  • Eat a low histamine diet – some foods are extremely high in histamine including alcohol, fermented foods, processed or smoked meats, aged cheeses, and shellfish. Avoid these and focus on fresh unprocessed foods.
  • Ditch the leftovers – food that sits for a while, like leftovers, accumulates histamine while it sits so if you generally have a high histamine picture then leftovers may not be your friend. Make enough food for one sitting and cook fresh each time.
  • Vitamin C – vitamin C helps to prevent mast cell degranulation, which is the histamine-release event. In my own clinical experience, it is quite often a larger than average dose of vitamin C, and a buffered vitamin C product like Ester-C can be most effective.
  • Calcium – calcium helps to lower histamine levels in brain tissues and has a generally complicated relationship with histamine in mast cells – stimulating histamine release in some circumstances and regulating it in others. Some people seem to feel a direct and clear improvement in their symptoms with calcium supplementation and some people don’t notice anything.
  • Watch your folate levels – histamine increases with increasing folate, and often people with folic acid toxicity have problems with high histamine levels. Also, people who are supplementing with too much folate in any form – even the good ones like 5-LMTHF – can experience high histamine symptoms.
  • DAO enzyme – DAO, remember, is one of your main histamine breakdown pathways and a DAO supplement can help tremendously, especially if you experience a lot of histamine release directly related to foods. Still eat a low histamine diet if possible, but supplement a DAO enzyme to help your body calm down.
  • Try Quercetin – quercetin is well known and well researched to inhibit histamine production and to reduce pro-inflammatory mediatiors. For allergies it should be taken in a higher dose. Around 400 mg twice daily away from food is most common.

Thank you so much for listening today and it’s official – a free MTHFR Basics course has launched at and an in-depth MTHFR for Life course is coming soon. That one will need beta testers who will be able to attend the course for 1/4 of the usual price, so please do sign up for the mailing list at, or on the courses page.

One of the best way to deal with high histamine is to make changes in your diet. While some foods and vitamins for histamine intolerance can moderate the excessive levels in the body, there are certain foods that contain histamine in high amounts and can cause inflammatory reactions.

Some of the food items that may cause histamine food allergy are:

  • Fermented foods like sauerkraut, yoghut, kimchi, vinegar
  • Processed meats
  • Alcohol
  • Leftovers
  • Slow-cooked bone broth
  • Dried fruits
  • Shellfish
  • Aged cheese
  • Avocado
  • Dairy products
  • Eggplant
  • Spinach

Aside from the diet changes including replacing the high-histamine foods with low-histamine fresh foods, there are ways you can help balance your histamine levels. 

You may have to use a combination of strategies to help:

  • Balance your methylation to optimize histamine clearance
  • Use a DAO enzyme supplement to help clear histamine faster
  • Use antihistamine herbs such as quercetin, NAC, stinging nettle, bromelaine, or butterbur
  • Use over the counter antihistamines as needed

Histamine intolerance is often difficult to diagnose because the symptoms overlap with many common problems. Symptoms arise in many parts of the body and can affect the gut, lungs, skin, and brain. People diagnosed with histamine intolerance can feel excess histamine symptoms such as:

  • Bloating
  • Diarrhoea
  • Nausea
  • Headaches
  • Hives, rashes, or itchy skin
  • Congested and/or runny nose
  • Red, itchy, or watery eyes
  • Dizziness
  • Heart palpitations
  • Abdominal pain

Some of the lesser-known, but common allergic responses and symptoms are:

  • Low blood pressure
  • Shock
  • Narrowing of airways

When histamine accumulates in the body a person can develop histamine intolerance or histaminosis. Histamine problems mostly occur when the enzymes Diamine oxidase or DAO and Histamine N-Methyltranferase, or HNMT fail to break down the histamine properly. This can be due to genetic issues with DAO or HNMT, or related genetic issues like MTHFR. Roughly 1% of the world’s population suffers from a histamine disorder.

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MTHFR is a common genetic mutation that can contribute to anxiety, depression, fatigue, chronic pain, infertility, and more serious conditions like breast implant illness, heart attack, stroke, chronic fatigue syndrome, and some types of cancer. If you know or suspect you have an MTHFR variant, schedule a free 15-minute meet-and-greet appointment with MTHFR expert Dr. Amy today.

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Amy Neuzil
Amy Neuzil

Dr. Amy Neuzil, N.D. is a leading expert in MTHFR and epigenetics, and she is passionate about helping people achieve optimal health and wellness for their genetic picture. She has helped thousands of people overcome health challenges using a simple, step-by-step approach that starts with where they are today. Dr. Neuzil's unique approach to wellness has helped countless people improve their energy levels, lose weight, and feel better mentally and emotionally. If you're looking for a way to feel your best, Dr. Amy Neuzil can help. Contact her today to learn more about how she can help you achieve optimal health and wellness.

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