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Don’t fear the fridge! Histamine intolerance is bigger than food

Histamine intolerance.

A real condition with a very unfortunate name.

No one is actually “histamine intolerant,” we all need histamine, it’s an essential neurotransmitter.1 However, as with anything, too much of a good thing can cause problems. When more histamine accumulates than our body can handle, symptoms begin which means “histamine intolerance.” Under this definition, every one of us is histamine intolerant, as heavy doses of histamine cause food poisoning.2

If you’re reading this blog, you’re likely in the midst of internet research, which can be useful. For example, I never understood until recently that it was an overload of histamine that sometimes caused my insect bites to swell beyond normal, and I wouldn’t have found this information were it not for commentators like Dr. Ben Lynch, who has written about having the same issue. So, yes, do your research. But a word of caution is in order as well. Before you go too far down the high histamine food list rabbit hole, it’s important to remember that histamine intolerance is multifactorial. Food gets all the attention, but food is just one of the issues that cause histamine to build up to unhealthy levels in the body. Severe reactions to high histamine foods are very likely a warning sign that one of the five factors I discuss below is out of balance, especially the microbiome.

As your histamine research continues, also be sure to check out the podcast we did on “The Histamine Leaky Gut Connection.”

For me, one of the aggravating issues was getting my wisdom teeth out while living in a region of the country where I have severe allergies. Wisdom teeth surgery equals antibiotics and high dose NSAIDs, both of which kill off healthy gut bacteria, lower levels of diamine oxidase (the enzyme our bodies use to clear histamine) and invite the spread of pathogens, like Candida, that can help cause reaction to high histamine food, or really just cause immune cells to go haywire in the first place.

But remember, all food contains some histamine. Even if you suspect you have an issue with histamine intolerance, you are not permanently unable to deal with histamine, you just need to do some digging to get a handle on what is the primary driver behind your overactive immune system.

Consider this quote from Chris Kresser:

Histamine intolerance is unlike other food allergies or sensitivities in that the response is cumulative, not immediate. Imagine it like a cup of water. When the cup is very full (high amounts of histamine in the diet), even a drop of additional water will cause the cup to overflow (symptoms activated). But when the cup is less full, it would take more water (histamine) to cause a response. This makes histamine intolerance tricky to recognize. 

What Causes Histamine Intolerance?

So, what factors contribute to the histamine overload Chris references?

There are five big ones. 

  1. Allergic reactions to allergens like pollen, dust and ragweed
  2. Diminished genetic ability to clear histamine
  3. Compromised gut health that is producing histamine, or unable to clear it
  4. Lifestyle: stress and substances that block histamine clearance, like NSAIDs and alcohol
  5. Food that is high in histamine (biogenic amines)

#1 Allergy and environment

This is a big factor almost no one talks about, but allergy to the environment triggers the immune system to produce histamine, which starts to fill the histamine bucket. 

In my experience, especially when the gut has been compromised, seasonal allergies alone can bring histamine levels to the very top of the bucket. For example, immediately after my wisdom tooth ordeal, I couldn’t eat the same way in Austin, Texas as I did when I spent time on the California coast, especially during grass pollen season in Austin. The air-borne allergens took up a good chunk of my histamine bucket, leaving me with reduced wiggle room for food. I would react to foods in Austin that I did not react to in Sonoma for example. The same was true for supplements. I benefit from Lions Mane in California, but because Lions Mane produces Nerve Growth Factor (which is also produced by mast cells when they degranulate and release histamine), I don’t tolerate it as well in Texas, and even experienced intense itching on my arm, which is a known side effect.

In the quote I included above, Chris talks about a “full histamine glass” due to high levels of histamine in the diet. But what about the scenario where the glass is full due to seasonal allergies? If you live in a city where your allergies are particularly bad, your body is constantly producing histamine independent of what you eat. This means that location alone can be the cause of histamine intolerance.

To this point, Dr. Janice Joneja wrote an excellent blog post on the subject of histamine that everyone should read. This quote stands out as particularly important:

A person with histamine intolerance will typically experience a constant fluctuation in the signs and symptoms of histamine excess in response to changing conditions. For example, when a person is experiencing allergy to air-borne allergens such as seasonal pollens, the histamine released in the allergic response alone might put them into the symptom range. In such a case, avoiding histamine-associated foods will no longer relieve their symptoms because their total level of histamine will remain above their limit of tolerance. This explains the observation that during their “pollen allergy season” many people find themselves reacting to foods (usually histamine-rich foods) that they could normally eat with impunity.

Dr. Joneja’s commentary explains why some people feel so much healthier on the coasts. In fact, there are whole communities of people who rate places they’ve lived based on how they felt in that location. Described as the “locations effect,” those suffering from chronic fatigue and mold sensitivity have described significant improvement when they visit certain climates, especially coastal and arid climates.

For more on the Locations Effect, take a look at the podcast episode we did with Erik Johnson, founder of the movement.

A word of caution about the locations effect groups. While their stories are useful in understanding that one’s physical health can be affected by location, and dramatically so, becoming phobic of place after place due to an often vague notion of “mold toxins” is I believe a sickness mentality that will keep people feeling unwell. The goal is to enjoy our food and to enjoy our homes. I mention the locations effect community because I think location plays a larger role in health than the medical community recognizes, but the “extreme mold avoidance” lifestyle, is in my view, just another high histamine food list – an unsustainable lifestyle that prevents full participation in, and enjoyment of life.

Now, having said that, I recognize that there are some people who have such great sensitivity, that they can only thrive in certain environments. My discussion above is not intended to marginalize these groups, but rather to encourage those of us with more benign issues, not to take this location issue too far.

Nonetheless, when the impact of location comes on your radar, you start to realize how much of an impact it can make.

For example, a good friend’s wife was just telling me how amazing she felt in Croatia, and how that all went away when she came back to southeast Michigan. Her puffy eyes and sniffles returned with abandon. Similarly, I’ve noticed that I feel incredible after just a few days in Southern California. I don’t believe this is a coincidence for either of us. San Diego and coastal Croatia are both mediterranean climates where Texas and Michigan allergens are largely non-existent.

It makes logical sense we’d both feel better in climates where we have very few allergies.

Related to this issue of allergy and mold avoidance in the chronic fatigue community, which at their essence are issues rooted in air quality, if you’re having issues with histamine intolerance, it may not be a bad idea to identify potential mold exposure in the past. Mold toxins will cause mast cell activation, which is the process your body undergoes when it releases histamine and other inflammatory substances from immune cells. If a portion of your body has been colonized by mold toxins, conditions like histamine intolerance may not be far behind. Detoxifying from the mold exposure could be what solves the histamine issue, because it could be the chronic release of mold toxin into your body that is driving the activation of your immune system. 

To find out if you have elevated mold toxicity, there are two labs that offer high quality mycotoxin panels: Real Time Laboratories and Great Plains Lab. These are both simple urine tests, but elevated mycotoxins from these labs indicate an issue with mold.

For a discussion of how mold toxins link with mast cell and histamine issues, I have included with interview with Dr. Neil Nathan, a mold and mycotoxin expert and clinician.

#2 Genetics

Note: finding a genetic marker for histamine intolerance does not necessarily mean you will have trouble clearing histamine, it serves as a “clue” to dig deeper into lab work and symptoms.

There are two primary enzymes that break down histamine in the body: diamine oxidase (DAO), and histamine N-methyltransferase (HNMT).34

Both DAO and HMNT production are coded for specific genes. The AOC1 gene makes DAO, and the HNMT gene makes HNMT.

So as not to confuse the DAO enzyme with the DAO gene, take a look at Aaron’s post: You say DAO, I say DAAO.

DAO breaks down “free histamine,” like the histamine found in the gut, while HNMT processes histamine in the cell.  Variants in the AOC1 gene have been associated with reduced DAO activity. This Italian study found that 10 out of 14 patients with histamine intolerance had very low levels of serum DAO.

The thing to remember about DAO is that not everyone has the same amount, and that your day to day habits play a role in shaping your DAO levels. Some people are genetically more efficient at clearing histamine than others, and lifestyle factors can either improve, or inhibit, DAO levels. Antibiotics, alcohol, local anesthetic and NSAIDs, like Motrin, all further reduce our natural ability to clear histamine by reducing DAO levels.

Aaron’s research indicates that histamine issues often coincide with gut problems because histamine, when chronically elevated in the gut, can cause an increase in zonulin, which is a protein shown to break apart the epithelial wall, which is the lining that keeps the contents of the gut from entering the blood stream.

For more on gut health and histamine, take a look at the podcast episode we did on the subject.

One of the factors we use to categorize people into diet groups for the custom nutrition plans is histamine clearance.

#3 Gut Health

Mast cells reside in large numbers in the gut, so a chronic allergic response paired with an inability to clear the histamine (due to reduced DAO) will irritate the gut over time.5 According to Dr. Nathan, mold and fungus tend to colonize the gut and the sinus areas with the greatest frequency and this colonization could be contributing to mast cell activity in some with histamine issues.

Decreased DAO levels are linked to a number of inflammatory bowel conditions, including Crohn’s disease and ulcerative colitis.6 I list leaky gut as a condition that can be caused by allergy in my post 6 strange conditions caused by allergies.

To make matters worse, many fermented foods, marketed for “gut repair,” actually produce histamine. Collagen is a bad one in this regard. 

High protein diets and histamine

Even undigested animal protein can ferment in the gut causing histamine levels to rise.7 Excessive protein consumption is one that doesn’t come up in most histamine discussions (many proteins are listed as “safe”), but histidine is an amino acid in protein that converts to histamine.8 Too much animal protein can cause histamine levels to rise, and your ability to digest protein can be a function of blood type. Although the blood type diet has largely been debunked, the one redeeming scientific feature is hydrochloric acid levels in the stomach. There is actually good science that shows a strong link between certain blood types and their stomach acid levels. Those with more hydrochloric acid, usually type O, have a greater ability to digest animal protein than those with the least (usually type A). If you’re not sure where your stomach acid sits, some doctors recommend taking a hydrochloric acid supplement and seeing whether you feel reflux or burning. If you do, you have adequate stomach acid. If you do not, stomach acid may be on the low side. Dr. Joel Evans, MD discussed this method in our food sensitivities podcast.

For more on that subject, check out: The blood type diet has been debunked, or has it?

Not sure what to eat?

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SIBO and histamine

There also appears to be a link between small intestine bacterial overgrowth (SIBO) and histamine intolerance, with some people reporting renewed ability to eat histamine rich foods after following a SIBO protocol. This story is extreme, but provides a nice example.

Avoid NSAID products

Further, there appears to be a link between SIBO and NSAID use.9 For people with an already diminished capacity for clearing histamine due to decreased DAO levels, NSAID use could make matters even worse. If you’ve had a recent life event that necessitated use of NSAIDs, it could be the cause of SIBO and histamine intolerance. In fact, certain variants in teh AOC1 genes are associated with NSAID allergy. 10

#4 Lifestyle

Lifestyle choices can impact histamine levels in a big way. How we live, what we put in our bodies, and stress levels all contribute to how we handle histamine.

In my case, histamine issues worsened after having my wisdom teeth out.


Prior to the operation, my doctor asked that I take a few days of antibiotics prophylactically as a precaution against infection. Taking antibiotics has been proven to inhibit DAO activity. Of course, I also took local anesthetic, another known DAO inhibitor.4 I also reluctantly took high dose Ibuprofen for a number of days after the operation to ease pain, which is another big no no when it comes to histamine. This is especially the case if you have certain SNPs in the AOC1 gene.10

Both antibiotics and NSAIDs limit DAO production. In doing research for our guide to Genetics and Nutrition, Aaron added NSAIDs as contraindicated for the T allele of ACO1 rs10156191.

So, as you can see, I stumbled upon the perfect storm of lifestyle factors that can add up to histamine intolerance. I took antibiotics, NSAIDs, and local anesthesia, all while living in an environment where my allergies are severe.

What are some other lifestyle factors that can contribute to our histamine bucket overflowing?

Believe it or not, strenuous aerobic exercise releases histamine.11 This is not to say exercise should be avoided, it’s just meant to point out that lifestyle factors play a role in the amount of histamine circulating in our bodies.

Alcohol is another big one. Alcohol, especially red wine, contains high levels of histamine, and is also a DAO inhibitor. If you have histamine issues, it’s best to cut out booze altogether until you can right the ship. 

#5 Diet

In the histamine intolerance blogs I’ve read, diet is usually mentioned first, perhaps because it’s easiest to control. However, as this post discusses, the other four factors listed above will directly affect what foods you can handle.

If you’re living in a city where you have very few allergies, have good stress management and strong histamine genes, your likelihood of developing histamine intolerance goes down.

If you’re drinking alcohol all the time, eating sugary foods and taking antibiotics whenever you catch a cold, your likelihood of developing issues with high histamine food goes up.

The goal is to decrease your histamine load so that you have more room for error when it comes to food, because if you follow a histamine free diet for long enough you will effectively starve yourself. 

Key Takeaways

  • Histamine intolerance is multi-factorial – starting to react to food is a sign that some other upstream factor is amiss.
  • Physical location plays a role in histamine intolerance.
  • Ruling out mold toxicity and examining the health of the microbiome are worthwhile exercises when histamine intolerance strikes.
  • Alcohol, antibiotics and NSAID drugs are kryptonite for those suffering from histamine intolerance.
  • Some people are at a genetic disadvantage in clearing histamine.

John O'Connor

John O'Connor is the founder of Gene Food, host of the Gene Food Podcast and a health coach trained at Duke's Integrative Medicine Program. Read his full bio here.

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