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14 Facts About Histamine Intolerance To Help You Get Healthy

As evidenced by this excellent paper in the American Journal of Clinical Nutrition, histamine intolerance is a condition that is starting to gain more awareness in the medical community.

It’s a problem I have battled with in the past, and one that can seriously degrade anyone’s quality of life. Based on my experience with histamine issues, and after our research team spent over 100 hours combing through all the relevant peer reviewed studies on histamine and histamine metabolism, there are 14 things we’d like you to know about this condition.

It is our hope that the information we share in this post will help some of you as you battle through this difficult time, but before we get started, some words of optimism.

First, you can get a handle on histamine intolerance, it’s not easy, but you can beat it with a personalized approach.  

Next, and this is crucially important – do not fear the fridge! Histamine intolerance is bigger than food. Ultra restrictive diets with 100 foods to avoid aren’t the solution long term. In order to be healthy, you must eat. This doesn’t mean that low histamine diets can’t help, but food isn’t the whole story, as we will learn in this post, there are multiple factors that contribute to histamine overload.

With those preliminary notes out of the way, let’s get into the list.

#1. Histamine is a neurotransmitter

Yes, that is correct, 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. Each of us has a histamine bucket. As our bodies make histamine, and as we ingest it in food, it is cleared by an enzyme known as diamine oxidase. When more histamine accumulates than our diamine oxidase levels can handle, symptoms begin which leads to the condition known as “histamine intolerance.”

#2. Histamine is released from mast cells

We can eat histamine, our brains use histamine, and the immune system also releases histamine from a special class of cells, called mast cells. Think of mast cells as the military sentinels of the immune system.

When these cells see a foreign invader, like a virus, or allergen, they react by “degranulating” and releasing cytokines that can seek out and kill the invader. Histamine is released from mast cells as part of this process. It acts as a vasodilator to facilitate blood flow to injury sites in the body.

The key thing to understand when experiencing histamine intolerance is that mast cells can become chronically irritated, causing the near constant release of histamine. We need mast cells for a properly functioning immune system, but they also need rest. When bacteria, or an environmental toxin, or an allergy continues to trigger mast cells, the resulting cytokine activity can start to cause tissue damage which leads to chronic inflammation.

Based on the commonly reported symptoms of histamine intolerance, it probably won’t come as a big surprise that mast cells are found in greatest numbers at the site of mucous membranes: skin, nose, throat, gut, lungs, and bladder.

In a very real sense, the quest to get over histamine intolerance is the quest to discover what it irritating the immune system and to remove it from the equation. Histamine intolerance can also be misdiagnosed as mast cell activation disorder.

#3. Excess histamine causes food poisoning

You may have heard the expression – “the dose makes the poison.” If you have one bourbon, you have a great time. If you have the whole bottle, you end up in the hospital. The same principle applies to dietary histamine. At a high enough dose, every one of us is histamine intolerant, as large doses of histamine cause food poisoning.

#4. One percent of people suffer from histamine intolerance

The American Journal of Clinical Nutrition estimates that 1% of the population suffers from histamine intolerance and 80% of those patients are middle aged. Because the symptoms of histamine intolerance overlap with many other conditions, struggles with histamine often go undiagnosed. For me, one of the biggest signs that my histamine levels were out of control was “normal” bug bites that would swell out of control. It took me years, and the insight of an excellent physician, to understand that this issue was related to histamine and allergy.

#5. Seasonal allergies can contribute to histamine intolerance

This is a big factor that isn’t discussed as much as it should be. Food gets all the attention, but histamine intolerance goes well beyond food. Allergy to the environment triggers the immune system to produce histamine, which starts to fill the histamine bucket.

Consider this quote from the American Journal of Clinical Nutrition: 

Underlying conditions for increased availability [of histamine] may be an endogenous histamine overproduction caused by allergies…

In my experience, seasonal allergies alone can bring histamine levels to the very top of my bucket. For example, I couldn’t eat the same way in Austin, Texas, a city where I have severe allergies, as I did when I spent time on the California coast, especially during grass pollen season in Austin.

The production of histamine by air-borne allergens took up a good chunk of my histamine bucket, leaving me with reduced wiggle room for food. This means that location alone can be a 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.

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.

#6. Histamine intolerance has a genetic component

I touched on this at the outset, but an enzyme called diamine oxidase is responsible for cleaning up histamine in the gut. 2 The AOC1 genes are coded to make this important enzyme, but not everyone is born with the same enzyme activity, which makes some of us genetically more susceptible for developing histamine intolerance.

So as not to confuse the DAO enzyme with the DAO gene (which many online forums do) 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, another histamine gene, processes histamine in the cell.

Variants in the AOC1 genes have been associated with reduced DAO activity. For example, this Italian study found that 10 out of 14 patients with histamine intolerance had very low levels of serum DAO.

#7. Histamine intolerance can cause gut issues

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.

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.

Decreased DAO levels are linked to a number of inflammatory bowel conditions, including Crohn’s disease and ulcerative colitis. This small study, which evaluated tissue samples from the intestine of 20 patients struggling with Crohn’s, found that all of the patients had very low levels of DAO.

To make matters worse, many fermented foods, marketed for “gut repair,” are very high in histamine. Collagen is a bad one. 

Not sure what to eat?

Gene Food uses a proprietary algorithm to divide people into one of twenty diet types based on genetics. We score for fat metabolism, histamine clearance, carbohydrate tolerance, and more. Where do you fit?

Learn More

#8. Our microbiome can produce histamine

Changes to the flora in our guts may be a contributing factor to histamine intolerance, which is why some of us develop histamine problems after a severe infection and multiple rounds of antibiotics.

Small scale studies have shown that the microbiomes of those with histamine intolerance are altered in noticeable ways. Again, the studies aren’t enormous, but patients with histamine intolerance have been found to have elevated levels of Proteobacteria above what is considered normal.  Proteobacteria are a type of microbe found commonly in disease states.

Further, healthy microbes in the gut, like many Bifidobacterium species can degrade histamine, while other unhealthy microbes, such as Escherichia, can produce histamine. 3

#9. NSAIDs can aggravate histamine intolerance in some people

Certain variants in the AOC1 genes are associated not only with lower levels of diamine oxidase, but with NSAID allergy as well. The SNP in question is rs10156191.

Carriers of the T allelle, which is also linked to lower DAO activity, are likely to have a hypersensitive reaction to NSAID drugs.

#10. Alcohol makes histamine intolerance worse

As we’ve established, one factor in the body’s ability to deal with histamine is genetic, however, lifestyle also plays an important role.

You may have read that alcohol degrades DAO activity, which further worsens histamine issues. This is a widely reported “fact” on the internet, but the evidence is limited. Having said that, drinking alcohol is not good for you under normal circumstances, but it’s especially bad if you are suffering from histamine intolerance.

Most alcohol, and especially beer and wine, is fermented and very high in histamine. If you’re looking for a drink to quickly fill and overflow the histamine bucket, it’s booze of any kind. Some people report success sticking to clear liquor rather than beers, wines, and liquors with more additives.

This study, which appeared in the Journal Allergy and Asthma Proceedings, evaluated the histamine levels of 28 wine intolerant subjects before and after drinking red wine. Within 30 minutes, 22 of the subjects saw their histamine levels sky rocket.

#11. All food has histamine

In some cases, especially when medical supervision is present, a low histamine diet can be just what the doctor ordered to help curb a problem with histamine intolerance. However, it’s important to recognize that almost all food has some histamine. Known as a “biogenic amine” histamine in food accumulates the longer food sits out, and is especially bad in aged and fermented foods. However, it is impossible to completely avoid dietary histamine. When I have tried eating an ultra strict low histamine diet, I’ve lost weight and felt miserable. All of us, regardless of whether we have histamine problems, must eat to be healthy.

#12. Freshness of food is key

Why is red wine such a problem? In part because it’s aged and fermented. That’s part of what makes it delicious, but that’s also what makes it high in histamine. The same is true for:

  • Leftovers
  • Smoked meat and fish
  • Deli meat
  • Aged cheese
  • Meal prep services
  • Fish that is not fresh
  • Avocado and banana

Any food given time to ripen or age will only increase in histamine the longer it sits out. Keeping an eye on the freshness of food is key if your goal is to defeat histamine intolerance.

#13. Elimination diets can be easier than you think

If the thought of cutting out 100 foods to go on a low histamine diet scares you, you’re not alone.

Even the list I cite above seems rather large, doesn’t it? Well, if you want to experiment with food triggers, and go low histamine, start by cutting out the least nutrient dense foods and move on from there.

What does this look like?

It means ditching the condiments. Pickles, sauerkraut, ketchup, salsa. These foods are notoriously high in histamine, and although they are tasty, they confer very little in the way of nutrient density.

Next, get rid of the booze, especially the heavily fermented kind, and sorry, but no more cold cuts, leftovers, aged cheese, and smoked salmon.

Oh, and take a break from coffee and tea. They are both histamine liberators, but more simply, they contain caffeine which increases cortisol. Most people with histamine issues need to balance stress as a first priority because…

#14. Stress makes histamine intolerance worse

At the beginning of this post I wrote about the role that mast cells play in histamine intolerance. There are a myriad of factors that can trigger mast cells, but stress is one of them.

High stress environments will make a case of histamine intolerance worse. Consider this review by world renowned mast cell expert Dr. Theoharis Theoharides in which he discusses the stress response and its impact on the immune system.

For interested readers, we interviewed Dr. Theoharides on the podcast last year.

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, a nutrigenomic startup helping people all over the world personalize nutrition. John is the 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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95 Comments

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  1. Lieve says:

    I get constant headaches and can often not pinpoint the culprit food. I get stuffed sinusses and insomia as well. I has SIBO but had the problems already before but maybe not as severe. I follow the diet using the Swiss HIT list but right now it doesn’t seem to help much. DAO by Seeking Health doesn’t seem to do anything for me. Any ideas? Anyone getting headaches from HIT? Thanks!

  2. Genius Turner says:

    Thanks for the excellent post, John.

    Of late I’ve noticed there appears to be a correlation between body heat and mast cell activation. Namely, after a round of exercise I invariably notice a small number of hives; it’s as though histamine sufferers would be best served to monitor the inflow/outflow of energy. In short, everything from caffeine and heat, in general, which is a form of energy, all seem to trigger histamine.

    At any rate, thanks for the insight! Keep up the good work.

  3. Jean-Pierre says:

    Some good info here, but some bad advice too. Apple Cider Vinegar is a definite no no for those with histamine intolerance.

  4. Christina says:

    Just curious, have you had allergy testing? Did you test positive for seasonal allergies? I have read most histamine intolerance responses are not true ige allergies.

  5. Elaine Moore says:

    Great article. I have an irregular heartbeat and palpitations when i take most probiotics but don’t have any significant symptoms from tea, red wine or cheese. I’ve ordered diamine oxidase and some probiotics with non-histamine producers. I do have the SNP mutation for low diamine oxidase and i take many antioxidants. Is this primarily a gut issue?

  6. Femke says:

    Thanks for this very clarifying article. This completely explained what I have suspected these last couple of months. I’ve had a stressful period followed up by my season allergies and ‘all of a sudden’I’m histamine intolerant. With very severe complaints. For e.g: Can’t eat tomatoes without lying wide awake at the moment and having heart palpitations and heat flushes while during winter I eat a lot of tomatoes without any problem. Had some issues with food during earlier springs, but not anything like this…. Love that you mentioned Dr Janice Joneja, think she’s fab. Thanks again, xx from the Netherlands

  7. jodi says:

    My 8 year old son has suffered from severe environmental allergies since he was 2. He takes a high dose of anti-histamines daily along with flonase and asthma medication. In the spring though, the higher levels of pollen cause him to develop anxiety. It has been suggested to me that he needs to lower the candida levels in his gut. Any suggestions on how to do this without a major diet change? He eats well balanced meals, but he’s 8 so there are snacks in there and I’m not going to be able to get him to eat buckwheat porridge.

  8. Gino Côté says:

    Greay article but you are confusing High Histamine with Histamine liberator. For example, Coffee is not hight in Histamine its a Histamine liberator. It contain zero Histamine.

  9. martha says:

    I would like to understand the relationship between histaminosis due to DAO deficit and high ammonium levels. From what I’ve read in your fantastic blog, the answer may be in the low levels of gastric acid? Can a high protein intake in the diet increase ammonium and histamine at the same time by these low levels of gastric acid?
    On the other hand, is it possible to have headaches when it rains or the weather is humid due to a problem with mycotoxins?Thank you so much…great job 🙂

  10. Samia says:

    Hi John,
    Do you ever take antihistamines during allergy season? Natural remedies don’t seem to work for me when the weather is particularly bad (usually rainy days with mild temperatures). I used to take Zyrtec daily and when I stopped my symptoms came back 100x worse so I’m always hesitant to take any antihistamines but my allergies are unmanageable right before spring. Would be grateful for any insight!

    • Hey Samia, yes, I do. I will intermittently take loratadine and Zyrtec on and off when I feel my allergies are particularly bad. I do not take them everyday for any extended period.

  11. Mick says:

    Hi John

    1. I feel you’ve forgotten to highlight an import point. You mention it once during the above but don’t mention it agin.it’s Lectins [” the pressure cooking process completely eliminates the lectin in buckwheat, but not in oats”]. I think avoiding high Lectins foods is an important thing and if you are going to eat high Lectin foods, do what you mention and pressure cook those foods as it destroys the lectins.

    2. HealingHistamine website has some good recipes for a low histamine diet. Sadly Yasmine past away but the family is still looking after the website and taking orders for her books [i’ve got one of the cooks books and its great]. Yasmine’s focus was all about not getting bogged down in food lists of what NOT to eat and slowly expanding the diet – a sensible approach

    Thanks
    M

  12. Paula says:

    Hi John,
    This comment/question is long, so skip to last 6 lines for actual question!!
    I loved this post, but now I’m more confused than ever. I’ve been reading so much that my brain is about to explode. I have had symptoms of eczema all my life but they have gotten worse over the years. Tons of corticosteroids topical and orals when flair ups were bad. I never wanted to take those scary eczema drugs, so 7 years ago I went Whole 30 and found foods that triggered my eczema. Easy to avoid- if I chose to have any of those foods, I’d just be aware of accumulation, and limit other offenders—so to say, I practiced balance. Fast forward to this Dec, I started getting super itchy and literally pummeled my legs in my sleep— until bruised. (I had acrylic nails which are rounded edges instead of sharp so scratching won’t let you break skin, so I found out). I thought, wow, I guess I had a few too many cookies this holiday season. Continued itching all over my body beyond my normal eczema, but wasn’t putting anything together. I eat typically a 90% organic well-sourced diet that includes some animal protein. Did a Whole 30 again to ‘reset’ and get rid of those things previously identified and that I had been partaking (because I’m human), but this time, my eczema was getting increasingly worse and now had a rash on my trunk, neck, arms…WTH?? I started researching gut dysbiosis, I felt like despite my good food, I wasn’t absorbing any nutrients. I found GAPS diet and started the intro and got worse!! I felt tired, then got the flu. One thing lead me to another and I arrived here. Here’s the big, possible epiphany??…. I started thinking back and I remembered my PCP talked me into getting a flu shot, which I have always avoided, even though I am a dental hygienist and it is strongly recommended- not required. It seems all my terrible symptoms started about 2 weeks after that….I can’t find anything that may link HI to flu vaccines. Did my histamine cup runneth over?🧐 Am I crazy? Do I treat SIBO, leaky gut, or HI?I’m seriously confused, and feeling defeated.

  13. Sara says:

    Hi John, thank you for the excellent article, very helpful! I was just wondering what your thoughts on two things that I find skyrocket my allergy response:
    1. Sugar, sweets etc
    2. Lack of proper sleep!
    So why isn’t sugar mentioned anywhere regarding food histmane response or does it have an indorect effect on histamine production? Also I know that sleep has something to do with it because when i sleep late and get up early feeling exhausted I just have a very bad allergy day!
    One more question, how bad is canned tuna? I

  14. Marie says:

    I just want to clear this out; Tea is not good if you’re histamine intolerant, right (“the very worst offenders like aged cheese, tea and wine.”). But a pill with L-Theanine is ok? I’ve been drinking a lot of green tea since I thought it was good for me! But now I understand that I probably have histamine intolerance, can I change that green tea-drinking to a L-Theanine intake instead?
    Best Regards: Marie

  15. Diane says:

    Thank You, John.
    Glad to see you can approach this from a sensible perspective. I little rationalism can go a long way when we want to develop a lifestyle for long-term sustainability. Great ideas here!

  16. Carol says:

    Although I do understand why you are encouraging people not to freak out when they determine histamine is behind their symptoms, it does feel a bit irreverent towards those of us who have no choice but to hunker down and avoid the food. It is the only thing I CAN fully control, and, when I don’t control it I suffer drastically for it. When my histamine cup runneth over, regardless of the reason, experimentation has proved to me that I can eat only a narrow number of vegetables, and that is where I must stay for several months until the levels drop. Any deviations lead to an immediate undoing or exacerbation within 5 minutes of ingestion. I do take the important supplements to help assist, and eventually I can relax a little bit and try a few nuts, or a piece of bread. I can’t do what you describe for yourself and have a bit of high histamine here or there. Please don’t imply that we are going overboard or acting erratically if we have to jump all in. Often, we learn something valuable on that ‘jump in’ journey. Other than that, thanks for a great article.

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