Histamine Intolerance & the Gut

histamine intolerance and the gut

There is a strong connection between histamine intolerance and the gut. This inability to deal with high histamine foods in my patients with gut conditions like SIBO, coeliac disease and IBS is something I see in the clinic every week. 

Today we will be covering the science behind histamine intolerance, the enzymes that help to break it down and why the gut is such an important player in histamine intolerance. 

In future articles I will explore the connection between gut infections, irritable bowel syndrome, small intestinal bacterial overgrowth, inflammatory bowel disease and mould/mycotoxin exposures causing or contributing to histamine intolerance. I will also be exploring herbs and nutrients to support histamine intolerance and stabalise mast cells. If ever you need a primer simply bookmark this article and pop back for a quick refresher.  

Before we dive into the details let’s get the basics out of the way

What Is Histamine? 

Histamine was discovered back in 1910. Twenty-two years later, in 1932, it was shown to be a major player in anaphylactic reactions. As a biogenic amine, histamine is synthesised from the amino acid histidine by a number of different payers in the body including mast cells, basophils, platelets, histaminergic neurons, and enterochromaffin cells (1).

Histamine plays a range of roles in the body (see image below) including

  • Smooth muscle cell contraction
  • Vasodilatation
  • increased vascular permeability
  • mucus secretion
  • Tachycardia
  • alterations of blood pressure
  • Arrhythmias
  • stimulates gastric acid secretion
  • nociceptive nerve fibers
histamine intolerance and the gut
Image taken from: Histamine and histamine intolerance showing all the roles histamine plays in the body.

How Is Histamine Broken Down

Today we are talking about histamine intolerance. 

The analogy I like to use for my patients is a bucket. I’m sure you have heard this one before but if not the description can be helpful. 

For most people their intake of higher histamine and histamine liberating foods isn’t a problem. While they are filling their bucket with histamine they have no problem breaking it down and eliminating it – ie emptying the bucket.

For histamine intolerant people their ability to empty the bucket is impaired leading to an overflow of histamine and the symptoms it causes. 

The science gets a touch more complicated involving enzymes like diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT) that are involved in breaking down histamine for elimination from the body. 

Which enzyme is used depends on where the histamine is in the body. 

histamine intolerance and the gut
Image taken from: Histamine intolerance: a metabolic disease?

Diamine oxidase (DAO) is stored in the epithelial cells that line our digestive tract and is liberated into circulation when prompted. It breaks down histamine outside of the cells and is mainly made in the small intestine and the ascending colon. 

On the other side of the coin histamine-N-methyltransferase (HNMT) breaks down histamine inside of cells (1).

Image taken from: Histamine and histamine intoleranceshowing the different enzymes that break down histamine. 

Symptoms of Histamine Intolerance 

The classic symptoms that make me think a patient is struggling with a histamine overload is a persistent headache above their eyes, sinus congestion, an inability to breathe through their nose (swollen turbinates), dark bags under their eyes, skin rashes and ongoing sneezing.

histamine intolerance and the gut
Image taken from: Histamine Intolerance: The Current State of the Art

When we look at the research we can see these and a number of other possible symptoms including (1)

  • Painful periods
  • Decreased muscle tone
  • Arrhythmias
  • Hives
  • Flushing
  • Asthma

Causes of Histamine Intolerance 

Now we are getting to the important bits. 

To keep it simple histamine intolerance is caused by either an increased intake or availability of histamine or impaired histamine breakdown. It is important to remember that this isn’t an either or scenario. Both can be playing a role in your histamine intolerance issues. 

This could be as simple as overindulging in high histamine foods like sauerkraut with every meal or it could be slightly more complex involving a downregulation in enzymes (DAO and HNMT) that break down histamine. Frequently I see both an increased intake and poor histamine breakdown as drivers in my patient’s symptoms.

histamine intolerance and the gut
Image taken from: Histamine, histamine intoxication and intolerance

Histamine Intolerance and the Gut

At first the connection between histamine intolerance or overload and digestive issues might seem vague. When we dive a bit deeper it is obvious. 

First histamine overload is connected to a number of digestive upset symptoms including 

  • Diffuse stomach ache
  • Colic
  • Flatulence
  • Diarrhea  

Pair that with the raised histamine levels and low diamine oxidase enzyme (the gut derived enzyme that breaks down histamine) in a range of digestive disorders like Crohn’s disease, ulcerative colitis, allergic enteropathy, food allergy, and colorectal cancer (1) and you can see why it is so commonly seen in the Byron Herbalist clinic. 

Some of the less obvious symptoms of histamine on the digestive tract include (2)

  • Cramping
  • Bloating 
  • Heartburn and reflux 

Histamine Degrading Enzymes and the Gut  

So we have covered the enzyme diamine oxidase (DAO) which is mainly produced in the small intestine in the intestinal villi (3).

It should come as no surprise that histamine intolerance is common in conditions where the villi is damaged and DAO is not being generated in abundance. If the villi are where the enzyme is made and they have been damaged then less of the enzyme will be made. 

A small study found that patients that found benefit from a low-histamine diet had low levels of DAO and that, once supplemented, this enzyme improved their symptoms (4). 

I think about DAO as the frontline defence against high histamine food. It catches and breaks down this biogenic amine before it makes it into systemic circulation. 

An interesting point here is that a low histamine diet in histamine intolerant patients actually raised suboptimal levels of DAO showing that avoiding histamine not only improves symptoms, it can address one of the root causes as well (5).

But low DAO is just one part of the complex puzzle involved in histamine intolerance and the gut.

Histamine N-methyltransferase is the second enzyme we have covered. This particular enzyme is responsible for histamine breakdown in the cells. As you may have guessed, methylation is at the core of how this enzyme functions using a methyl donor from SAMe to break down histamine (6). 

Don’t worry this won’t end up in a deep dive into methylation but it is important to pick this out, especially if you know you are a poor methylator and are suffering from histamine intolerance with no known root cause.

The Gut Balance and Histamine Intolerance 

I’m not talking about probiotics here. I think we are ages away from singling out one particular probiotic strain and saying it is a histamine producer so should be avoided in histamine intolerant patients. 

Even if one probiotic has been shown to produce histamine the net improvements in the digestive tract (antimicrobial action, gut healing, mucous generating, immune system toning, the list goes on) prevents me from thinking of them as contraindicated in every histamine intolerant patient. 

Instead, I wanted to explore the balance of the gut microbiota in histamine intolerant people. 

One interesting study found that histamine intolerant patients had elevated levels of zonulin, a marker of leaky gut found that can be tested for with The Complete Microbiome Mapping test. They also found increased levels of Proteobacteria, a pro-inflammatory and less-than-friendly group of bacteria, and reduced diversity (a major marker of imbalance). Finally they found low levels of Bifidobacteria in histamine intolerant people compared to healthy controls (7). 

What to Do About Histamine Intolerance

I have a mental checklist for patients coming to see me with digestive issues. Histamine intolerance is always near the top of that list and is important to rule out by symptoms, lab testing and finally, if indicated a low histamine diet for 2-4 weeks. 

With most diets I am quite flexible and think there is room for the 80:20 rule (80% of the time you can be strict, 20% of the time you can be slightly more relaxed). When using the low histamine diet as a way to test for histamine intolerance it is important to be strictly low histamine. Now you will never get to no histamine but it is important to give it a good effort so we can tell whether histamine is a contributing factor in your symptoms. 

That’s all from me for now. In future articles we’ll be diving into the nitty gritty of herbal medicine for histamine intolerance, different conditions associated with histamine intolerance. Who knows I might even put together a low histamine workbook and diet. 

Now over to you. Do you struggle with histamine? Let me know in the comments below what helped! 

References and Resources

  1. Histamine and histamine intolerance
  2. Histamine, histamine intoxication and intolerance
  3. Histamine Intolerance: The Current State of the Art
  4. Serum diamine oxidase activity in patients with histamine intolerance
  5. Serum diamine oxidase activity as a diagnostic test for histamine intolerance
  6. Histamine intolerance and dietary management: A complete review
  7. Microbial patterns in patients with histamine intolerance
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1 comment

  1. Hi I believe I am suffering from histamine intolerance caused from an antidepressant that I am trying to taper off, as I am learning now this medication also acts as an antihistamine, my symptoms range from heart palpitations and arrhythmia itching, my skin producing heaps of oil,muscle twitches and low mood and anxiety also my menses have been of track last couple of
    months. Could you please help me on what would be the best steps for me to take I want to get my health back.

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