- #1. Histamine is a neurotransmitter
- #2. Histamine is released from mast cells
- #3. Excess histamine causes food poisoning
- #4. One percent of people suffer from histamine intolerance
- #5. Seasonal allergies can contribute to histamine intolerance
- #6. Histamine intolerance has a genetic component
- #7. Histamine intolerance can cause gut issues
- #8. Our microbiome can produce histamine
- #9. NSAIDs can aggravate histamine intolerance in some people
- #10. Alcohol makes histamine intolerance worse
- #11. All food has histamine
- #12. Freshness of food is key
- #13. Elimination diets can be easier than you think
- #14. Stress makes histamine intolerance worse
- Key Takeaways
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
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.
#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.
#9. NSAIDs can aggravate histamine intolerance in some people
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:
- 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.
- 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.