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What is Histamine Intolerance? Part 2

Updated: Mar 15

Enzyme Deficiency or Sensitivity?

Intolerance is a vague word. If you look it up, you’ll find that it describes both an enzyme deficiency or a sensitivity. The problem with this definition is that these are two very different biochemical pathways in the body.

Previously in What is Histamine Intolerance? Part 1, we discussed histamine intolerance as it relates to diamine oxidase (DAO) deficiency. In this scenario, you may not be producing enough DAO in the GI tract to sufficiently break down histamine from the foods you eat.

In this segment we will expand on that definition by looking at histamine intolerance as a subset of mast cell activation syndrome (MCAS). In this situation, an intolerance can be defined as a sensitivity.

When it comes to histamine, both uses of intolerance apply. Confusing right?

Clearing the Confusion

Mast cells have over 100 different receptors on their surface. Some of these receptors activate the mast cells, while other inhibit them. This activation or inhibition occurs when a ligand or trigger binds to the receptors.

It is the activation of the receptors that stimulates the mast cells to release chemical mediators.

Remember this video we did a while back to showcase what it looks like when a mast cell is degranulating, and releasing some of those chemical mediators? Much like the image to the right here.

With MCAS there is too much of this activation occurring, resulting in an inappropriate or excessive release of chemical mediators. The mast cells are acting just like in the video below on a consistent basis.

Some of the receptors that activate when binding to mast cells include immunoglobulin E (IgE), toll-like receptors, cytokine receptors, receptors for stem cell factor, and receptors for neuropeptides and opioids. This means each of the highlighted words mentioned here are potential triggers that prod your mast cells to release a bunch of different chemicals.

For individuals struggling with non-allergic anaphylactic reactions, the MRGPRX2 receptor has been identified as the relevant receptor (1).

Let’s look at an example. Here is how two different receptors are involved in hives:

  • MRGPRX2 activation (degranulation) is involved in chronic spontaneous urticaria (2)

  • But with vibration induced urticaria, ADGRE2 is activated (mast cell degranulation and increase in histamine being release in the body) (3)

Histamine Sensitivity

Histamine intolerance as a sensitivity occurs because there are also histamine receptors on mast cells. This means that histamine in the foods you eat can bind to mast cells and activate them, which now triggers them to release more histamine in to your system. This is equivalent to turning your tap on 'full blast' when thinking of the sink analogy. It fills your sink up really quickly!

When the mast cell receptors trigger an inappropriate or excessive activation during histamine binding, it means that mast cells are sensitive or sensitized to histamine. Once again, it’s the activation of the receptors that is the trouble.

MCAS is a Better Diagnosis

The problem with being told you have histamine intolerance is that the words don’t adequately explain the complexity of the condition. The words suggest that histamine is the only trigger for the mast cell activation.

It makes people think that by reducing histamine via the food they're eating, their symptoms will resolve. Unfortunately, histamine is not the only thing contributing to the problem here!

Maybe someday there will be simple testing that will allow us to know which receptors are involved. Until then, diet is just one part of the journey to discover what your triggers are.

It’s important to recognize that histamine intolerance is a subset, and not the entirety of what is contributing to your symptoms.

Which one sounds like you?

Do you feel like eating high histamine foods is part of a bigger problem?

Wondering what your triggers are? Start here, and check this out.


All this starting to make your head spin?

We have a Master Class coming up soon that may be able to further help make sense of this, and help you identify what is going on in your body. Consider joining us at our next The Histamine Connection class. It's a free class we host online every month or so, and it's the perfect place to start.

In the class, we'll help you make that histamine connection for yourself, and get you started on solutions to reduce what's driving your symptoms. Register for the next class by visiting this page.  Let's get you feeling better!

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