Histamine intolerance is becoming more and more prevalent.

I have it.

I also have MTHFR and susceptible to methylation deficiency.

Given the prevalence of the MTHFR polymorphism, it only makes sense that the general population is also very susceptible to histamine intolerance.


I wish I knew I had histamine intolerance 30 yrs ago.  Now that I’ve addressed it, so many of my symptoms are gone – or managable.

If there are two things to try in order to reduce histamine intolerance:

  1. Creatine and Phosphatidylcholine
  2. Reducing stress (sleep, mindset, meditation, exercise, hobbies, adaptogens)

The issue is histamine intolerance can rear its ugly head anytime, anywhere.  You have to be ready for it and know how to deal with it.

Identifying if you have histamine intolerance is not easy – and it is COMMONLY missed.

The only true way to know if you have histamine intolerance or not is to go on a low histamine diet for a period of time.

Feel better?

You are then histamine intolerant.


You’ve joined the elite club of folks who actually understand what is ailing them.


Now – my job is to help you beat it.

Before we do that, let’s get into what histamine intolerance actually is.

Imagine a 5 gallon bucket.

You have a lot of things to put into that 5 gallon bucket: soap, toys, screwdriver, watermelon, your favorite cat who doesn’t sit still, a pound of sand and 2 gallons of water.

Obviously, you’re going to have issues.

You need to make some decisions.

What stays? What goes?

The cat must stay. You’d love the water to stay but your favorite cat told you otherwise. Sand is chosen as is the soap because you know your favorite cat is going to do something to the sand.

The rest stays behind and off you go with your favorite cat, sand and soap in the bucket.

You’re happy and all is good.

Ignore the people on the beach. They’ll get over it.

This is the same thing as histamine intolerance.

You have a bucket of histamine and your body requires histamine in order to function.

You need histamine to do a variety of things – such as:

  • get blood, ie nutrients and oxygen, delivered to various areas
  • pay attention
  • digest your food
  • move your bowels
  • enhance exercise

The ideal amount of histamine allows these things to occur – and occur perfectly.

As histamine levels increase, your tolerance for it goes down.

You start to get too much blood flow, have too much attention, moving bowels too often and your exercise is now affected negatively.

This translates into histamine INtolerance.

Your histamine bucket is overflowing.

You need to get rid of some of it.

How do you do that?

Not easy as there are many factors which increase histamine – and they should all be addressed.

The causative factors for histamine intolerance are many:

  • Genetic susceptibility (MTHFR, DAO, MAO, HNMT, PEMT…)
  • Pathogens (a number of which produce histamine or block methylation)
  • Nutrient deficiencies (B12, folate, B6, B2, B1, Zn, Cu, C, methionine)
  • Nutrient excesses (histidine, protein excess in general)
  • Medications (antibiotics, antacids and even antihistamines (long term))
  • Nutrient demands (stress, anxiety, lack of sleep)
  • Hormonal insufficiciency (adrenal fatigue)
  • Hormonal excess (estrogen)
  • Lifestyle (excessive exercise, alcohol)
  • Diet (fermented foods, high protein intake, aged foods, leftovers, citrus, fish)
  • Environment (high pollen counts, dust mites)
  • Associated conditions (leaky gut, IBD, IBS)
  • others which I cannot think of off the top of my head – if you think of one – post a comment below and share

There are three main genes which are central to processing histamine:

  • HNMT – which requires SAMe as a cofactor (and this requires an effective MTHFR enzyme to help produce SAMe)
  • DAO – which requires vitamin B6 and copper
  • MAO – which requires vitamin B2 and iron
  • NAT2 – which requires CoA which stems from vitamin B5

If any one of these genes are slowed or burdened, then the removal of histamine is slowed – and symptoms of histamine intolerance occur.

How can you see if these histamine-related genes are slowed down due to genetic polymorphisms?

Order a 23andMe genetic test and then run your raw data through StrateGene. I developed StrateGene with a team of researchers. We specifically have one section of the report dedicated to histamine metabolism. Here we show the genes associated with histamine breakdown along with the epigenetic controls and cofactors. Very cool seeing it graphically.

What are symptoms of histamine intolerance?


I want to share with you one of my favorite research papers of all time – as it is so beautifully done.

Here it is:
Histamine and Histamine Intolerance

But don’t make me jealous – come back and finish this article as that paper – while great – is not nearly as comprehensive as mine – especially in terms of how to deal with histamine intolerance 🙂 .

Signs and symptoms of histamine intolerance are difficult to identify because many have delayed reactions – we’re talking a few hours after eating possibly.

Common signs and symptoms of histamine intolerance:

  • flushing
  • rapid heart beat
  • profuse sweating
  • headache
  • migraine
  • food allergies
  • seasonal allergies
  • urticaria
  • prickly heat
  • large swollen mosquito bites
  • runny nose
  • bloody nose
  • car sick
  • seasickness
  • motion sickness in general
  • itchy
  • irritable
  • nausea
  • vomiting
  • higher sex drive (not really a problem typically but good to know)
  • asthma
  • exercise-induced asthma
  • stomach ache
  • menstrual cramps
  • chest tightness
  • loose stools
  • skin issues (eczema, psoriasis)
  • insomnia
  • and others which I am forgetting

This is a slurry of symptoms and issues, isn’t it?

This goes to show you that it is best to think WHY, HOW and MECHANISM of various conditions rather than focusing on the ‘condition’ itself.

Can you imagine a patient walking in with the list above?

They do.

Every day.

They’d have to go to a variety of different doctors:

  • dermatologist
  • pulmonologist
  • psychiatrist
  • gastroenterologist
  • gynecologist
  • endocrinologist
  • cardiologist
  • general practitioner

Then, each doctor is going to prescribe a variety of medications:

  • cortisone
  • antihistamines
  • SSRI
  • calcium-channel blockers
  • hormones
  • fiber

All of the above medications are palliative only.

They simply mask the symptoms and not one of them addresses the underlying cause.

In fact, some of them exacerabate the actual main complaints!!

This happens to thousands of patients – daily.

This has to stop.

Let’s look at it from the way doctors should be looking at this.

Instead of asking, “What is your chief complaint?”, it should be:

“Please list ALL of your symptoms from most aggravating to least aggravating.”

This way, the physician can see all of them and see if they are correlated.

Guess what?

They are.

The body is connected.

The brain bone is connected to the heart bone which is connected to the lung bone which is connected to the intestine bone.

Remember that song when you were a kid?!

I think the lyrics were a little different but the idea is the same.


Stop DISCONNECTING patients and spreading their organs from one doctor to another.

Instead, understand how their body works as a whole and why these various symptoms and conditions are related!!

If this patient walked into my clinic with all of these symptoms, I’d be evaluating:

  • lifestyle (sleep, hobbies, work, family, friends, enemies)
  • environment (zipcode, farming community, urban, location to wires, cell towers)
  • mindset (optimist vs pessimist, ‘not my fault’ vs ‘all my fault’, talker vs listener, how vs what, etc)
  • diet (usual foods – unedited – a journal is key here – including fluids)
  • supplements
  • meds (include OTC)
  • calendar of events (in utero to current – use a timeline of main issues in life – sickness, stressors, exposures, surgeries)

In terms of labs, I’d be evaluating (if a first office call and patient could afford them – otherwise would skip labs and wait to do it until I was stuck and patient not improving):

  • CDSA (comprehensive digestive and stool analysis with O & P x 3)
  • RBC fatty acids
  • Urinary organic acids
  • Plasma amino acids
  • Serum ferritin
  • Thyroid panel (free T3, free T4, TSH, rT3, anti-TPO, anti-TG)
  • Homocysteine
  • Methylation profile (SAM:SAH ratio)
  • Lipid peroxides
  • Vitamin D
  • Histamine (but not very good marker – varies a LOT – need to evaluate history)
  • Total IgE, IgG, IgM, IgA
  • CBC with chem panel
  • Genetic testing
  • and some others if needed

From Michael McEvoy via my Facebook page – I thought this to be an interesting comment and worthy of sharing here:
“Consistently I’ve observed a basophil % of 1 or greater to correspond approximately to a whole blood histamine of 60 or greater. A % basophils of 2 typically features a whole blood histamine greater than 150.”

It needs to be clear – CRYSTAL – that histamine intolerance is COMMON.

Now let me be clear on another point.

Histamine intolerance is ONE issue out of potentially many that are going on. This is why I outlined all the causative factors above. I am NOT saying that all you have to do is address histamine intolerance and that laundry list of symptoms will go away.

What I am saying is that histamine intolerance is a major contributor to a laundry list of symptoms and must be evaluated – in addition to other things.

This is why you need a health professional trained in methylation and nutrigenomics on your team.

I wish I didn’t have to always state the above disclaimer/disclosure but I must. People sometimes think that there is a magic bullet and constantly seek it. There isn’t. It’s complex and a team of health professionals is needed.

Back to addressing histamine intolerance.

A simple trial of what I am going to recommend is highly recommended for those suffering from a chronic long term variety of ailments which may come and go or just stay or get worse.

In order to reduce histamine loads, I typically recommend these things right out of the gate:

  • Diet: no fermented foods, no leftovers, no citrus, only FRESH fish or no fish, no alcohol, no aged foods. This includes cheeses, wines and processed meats. Limit protein intake to about 0.8 grams protein/2.2 lbs of body weight as protein provides histidine. Histidine transforms to histamine. Eat more fatty foods (healthy – like ghee) and whole grains (quinoa, wild rice). A more ketogenic diet would be great – but some cannot tolerate this (due to adrenal fatigue and electrolyte imbalance).
  • Lifestyle: sleep, reduce stress (huge), breathe (seriously), optimize exercise – don’t overdo it, laugh!, do things you love – don’t wait anymore.
  • Environment: new pillow, dust mite covers, clean the house, clean ducts, air purifiers, no air fresheners (dang things SUCK and are very nasty and contribute to histamine intolerance due to aldehydes), rip out carpet, install hardwood or tile, fresh air, drive with air recycle on whilst in traffic otherwise fresh air.
  • Mindset: positive, get it done attitude, empower, remove the ‘fix me’ mentality as it is the patient who must fix themselves and seek the right healthcare (which is NOT easy to do). Those of you who are struggling with this – I am trying my best to transform medicine and doctors are getting it. It’s a beautiful thing to watch evolve. We’re just beginning…. It is not just me doing it either – entire organizations are trying – such as IFM, AAEM, AANP and others.
  • Learn: give them reading material. Like Keto Clarity, The Metabolic Makeover, Think BIG, Aspire, I Can Do Anything If I Only Knew What It Was, …. Never stop learning.
  • Resources: The Low Histamine Chef – fantastic resource. I cannot vouch for all content though. Some is great and some is likely not. Kinda like here at MTHFR.Net – some of my articles are great – and others – ‘eh’.

Genetics which predispose you to higher histamine intolerance (just a few):

  • MAO: a gene which requires B2 as cofactor, is polymorphic, slower in men and reduces tyramines, histamine and catecholamines (stress neurotransmitters). Hmmmm. Riboflavin is great for migraine sufferers….
  • DAO: a gene which requires B6 and copper as cofactors, is polymorphic a LOT and reduces extracellular histamine (bacteria and food).
  • HNMT: a gene which requires SAMe as a cofactor, is polymorphic and reduces intracellular histamine.
  • MTHFR: helps regulate methylation which is needed to reduce intracellular histamine. Uses B2 as cofactor.
  • PEMT: produces phosphatidylcholine which is needed to for cell membranes – which keeps them stable and healthy.

There are common supplement recommendations which I use if the dietary, lifestyle and environmental changes are implemented.

It is NO use to take supplementation if you are going to just keep on living a life which is not conducive to health. A supplement is designed to ENHANCE – not to REPLACE basic lifestyle, dietary and environmental choices.

As one transforms their lifestyle, diet and environment – and mindset – many things resolve on their own – however, not always of course.

Supplementation requires all systems to be supported.

If any one system is unsupported, then symptoms of histamine intolerance may not resolve.

For example, a friend of mine has had allergies for longer than I’ve known him – which is over 20 yrs.

His allergies were improving significantly but the missing piece?

Supporting his adrenals.

After adding this in, despite a high pollen count, allergies were gone.

The more one adjusts and cleans up their diet, lifestyle, environment and mindset, the less supplementation is needed.

Also, at first, more supplementation may be needed to restore missing nutrients, eliminate pathogens, restore beneficial bacteria, stabilize cell membranes, restore gut health and adapt to stress.

Phew – that was me some time ago – and it also may be you.

I still suffer from histamine intolerance – and – always will – but with my changes all around, I have improved SO much.

My genetics predispose me to histamine intolerance – big time.

  • MTHFR compound heterozygous (1298 x 677) – check
  • MAO – slowed and male – check and check
  • DAO – multiple homozygous polymorphisms – check, check, check
  • HNMT – don’t know status but my MTHFR is messing with my methylation by itself – so already setting up my HNMT to struggle.

To give you an idea of my histamine intolerance situation:

  • Life long – but had no idea until about a year ago
  • Total IgE: elevated
  • CDSA: normal
  • CBC with chem panel: normal
  • Food allergy panel: high histamine foods came back high – lime, avocado
  • Consume histamine-containing foods: reaction – irritable, sweaty, insomnia, eczema, sweaty feet, rapid heart rate, nose bleeds (since I was a kid), tight chest.
  • Intolerant to alcohol – especially red wine
  • Serious dust mite intolerance
  • Huge mosquito bite welts
  • Tingling skin
  • Intolerant to heat

Having since cleaned up my lifestyle, diet, environment, gut, mindset and added supplementation, my histamine intolerance is now significantly improved.

It comes back fast, however.

On a flight to London, I wanted to sleep so I decided to drink some red wine.

Within 10 minutes, I had a nose bleed, faster heart rate and sweating.

I wanted to hit myself – but I already looked like someone hit me in the face so I didn’t make it any worse.

That goes to show you how fast it can come back – especially with slowed histamine metabolizing genes. I was also under stress – flying, work stuff and tired. I didn’t take my adrenal support….

Supplements which support methylation, MTHFR, histamine metabolism and histamine regulation: 

  • Histamine Block: useful when taking before eating foods/drinks with histamine. I should have taken this before the red wine – but it was buried in my bag located in the overhead compartment. This supplement contains the natural DAO enzyme which breaks food-derived histamine down. This may also be taken if your digestive system is full of histamine-producing bacteria. Talk with your doc. Get tested with the CDSA. Interesting fact: Pigs don’t get seasick as they have a TON of DAO enzyme and metabolize histamine very well. Hmmm – they can eat a ton of rotten food/leftovers and are fine with it….
  • HistaminX: useful to help reduce seasonal allergies or blunt histamine symptoms. Best to take in AM, afternoon and evening or as directed by your healthcare professional – during times of histamine intolerance. When not having symptoms, then only taking once a day or not at all is recommended. If I have a runny nose from dust mite allergies, I take one of these. It stops. It’s a new product so still experimenting with ideal dosing and recommendations.
  • ProBiota Bifido: a probiotic which supports a healthy flora but without increasing histamine-producing bacteria. Best to take after dinner and away from anti-microbials.
  • Optimal Liposomal B12 with L-5-MTHF: a higher dose of methylcobalamin and a little methylfolate to help support the methylation cycle. Great to give to kids or sensitive people and graduate the dose – drop by drop if needed or full dropperful or as directed by your healthcare professional. This is what I give to my son with histamine intolerance. He, like me, is compound heterozygous MTHFR, DAO snps and slow MAO. He doesn’t do well with that much methylfolate but he needs some – and this is what I turn to.
  • Optimal Liposomal Vitamin C: vitamin C is known to help stabilize mast cells and thus reduce histamine intolerance. The added phosphatidylcholine is supportive as well to cell membranes. Take anytime during the day with or without food. Some need food to reduce the acidity of the vitamin C.
  • Optimal PC (softgel or liquid): if methylation is hindered, then so is cell membrane formation. Did you know that 70% of your methylation is dedicated to making cell membranes?! If cell membranes are not made from the appropriate material – phosphatidylcholine, then inflammation and cell damage will occur. This leads to histamine release. Support cell membrane integrity by providing phosphatidylcholine with Optimal PC. Also eating eggs is a great way to get choline.
  • Optimal Creatine: if methylation is hindered, and it typically is in those with histamine intolerance, then creatine formation is likely hindered as well. Given that most of your methylation is used up to produce both phosphatidylcholine and creatine, wouldn’t it make sense to supplement with both of these in order to conserve methylation so it can then focus on reducing histamine?! Yes! It works! Using creatine that is bound to magnesium is way more effective than other creatines which may contribute to gas and bloating.
  • Optimal Fish Oil: useful to stabilize cell membranes which are inflamed and leaking histamine from mast cells.
  • L-Glutamine Powder or Optimal GI Powder: healing the intestines is key as the DAO enzyme lives in the intestinal wall. If one has leaky gut or GI inflammation, the DAO enzyme is not going to be present in nearly enough amounts. Healing the gut brings back the DAO enzyme – if it is not messed up like mine due to a genetic polymorphism. Regardless of a DAO polymorphism, one still needs to heal the gut. If your gut is healthy, then you can skip this step. If you get irritable from taking L-Glutamine Powder, back off the amount you are taking and support with Magnesium and B6. You likely have higher levels of glutamate and not getting it out fast enough. Magnesium Plus is useful to help metabolize glutamate.
  • Multivitamin which works for you: having comprehensive support – minerals, vitamins and others – is needed to optimize all pathways of histamine metabolism.


As mentioned previously, stress increases the demand of the MTHFR and MAO enzymes – and also methylation in general.

If you stress your methylation, you are on the road to histamine intolerance.

The bucket of histamine may overfill as your body has to deal with other things.

Thus, reducing and balancing stress is an incredibly important thing to do.

Get stress out of your bucket.

(I get into the science, reasons and mechanisms of how stress affects us negatively in a conference held in the UK. This is the best presentation I’ve done to date illustrating the negative effects of stress. You may access the recording here.)

The way to balance stress is multifactoral – as most anything.

  • Breathing: are you breathing properly? Seriously. Not a stupid question. Belly breathe, find good books and teachers – yoga is great to teach how to breathe. Are you holding your breath at times? Tune in to that. I found that I hold my breath sometimes when I am reading or writing….and I read and write a lot. I’m fixing this issue and trying to find out why I do it. Note – I think it comes down to histamine as I take a HistaminX and I seem to belly breathe more effectively – not as constricted. Still evaluating.
  • Oxygenation:  Work, be outside and sleep with your window open at least a crack. Get rid of the stale air and bring in fresh oxygen into your area and being. Increasing oxygenation reduces anxiety and stress.
  • Sleeping: are you sleeping well? Able to go to bed consistently, fall asleep, stay asleep and wake rested? If not, this is going to add to your stress – physical and emotional. Consider Optimal Sleep to support the nutrients needed for healthier and more effective sleep.
  • Eating: eat a balanced whole foods diet as much as possible. Limit large breaks between meals or at least eat when you feel hungry – don’t hold out. If hungry, eat. If not hungry, well then maybe you don’t have to but if your stress increases, go get some protein, healthy fats and quality whole grain carbs like quinoa or wild rice or veggies. Limit sugar as this will just cause a long term issue and spike your stress. Also don’t eat loads of protein as this just provides the building block to histamine – via the amino acid found in protein – histidine.
  • Adrenals: if your adrenals are burned out, so are you. Restore adrenals with the above recommendations. Supporting with nutrition and herbal interventions are also helpful for some. If you find you jump or are intolerant to stress, ie. yelling too much, quick to anger, scare easily, then you could use some adaptogens. I formulated Optimal Adrenal to help adapt to stressful situations and take the edge off – without being sleepy or losing focus. If tired upon waking and hard to get out of bed in the morning – and a night owl – then you may need something like Adrenal Cortex to really nourish your adrenals. Only take Adrenal Cortex in the morning with breakfast or as directed by your healthcare professional. You’ll find you need these nutrients some days and other days not. I only take them both periodically.
  • Exercise: if you have the energy, get out and burn some of it off by doing what you love. Sports, walking with a friend – and it can be a four-legged friend (there are some three-legged ones out there which is awesome to see them doing well Did you know I actually was studying to become an equine veterinarian? I changed course obviously). If you exercise, don’t push yourself past what you are comfortable in doing. If you do, you are going to stress your body, deplete your methylation and increase your histamine levels. Exercise-induced asthma?? Yes – you wore out your methylation and now your histamine levels built up and now you cannot run anymore. I’ll be addressing this here solely in an upcoming article and video. It’s surprisingly easy to fix. A key to supporting yourself during exercise is nourishing your electrolytes and mitochondria. If you do this, you can exercise more productively and optimally. Consider Optimal Electrolyte prior to exercise. It’s what I do and my three boys. People wonder how my boy won cross country for our district last season. Well – this is part of it. I have other tricks also 🙂 which I’ll be sharing when I do the exercise-induced asthma video (Free).

Can you cure histamine intolerance?


Can you maintain and support your body’s ability to balance histamine levels?


This is why this article is so long.

I had to teach you how to balance your histamine levels – by addressing a variety of pathways and mechanisms.

Go out and try some of these lifestyle, dietary and environmental tricks.

You’ll be surprised! 🙂

Symptoms which affected you your entire life will start disappearing and your friends will start asking questions.

With a smile, you’ll tell them you’re one skilled MTHF’R who knows the biochemistry of histamine.

Comment below how you support your histamine intolerance – and also how long you suffered with it prior to realizing you had it. How did you get your histamine intolerance diagnosed?

If you haven’t thought of histamine intolerance or didn’t know about it until now – what do you think? Going to try some of the above recommendations? If so – keep us all posted by posting a comment or two!

If you’re a health professional, are you seeing more and more histamine intolerance in your clinic? What are your tricks in resolving it in your patients? Did you find this article useful?

I’m loving this – one puzzle piece at a time. Knocking them out 🙂

Go knock out your histamine intolerance!

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