Jill Carnahan, MD

Mast Cell Activation Syndrome: Here’s What You Need to Know When Histamine Goes Haywire

Mast cell Activation Syndrome (MCAS)

If you’ve ever experienced a runny nose, sneezing, or watery eyes, then you’ve experienced an allergic reaction. Allergens are bombarding our bodies all the time, and this reaction is a highly protective response by your immune system when mast cells sound the alarm.

Mast cells, also known as “jack of all trades” immune cells, are intricately involved in your body’s allergic response.1 They’re your first line of defense against foreign substances entering your body, and their central role is to protect you. Without them, your body wouldn’t even be able to heal from a wound.

Mast cells are best known for the role they play in allergic and anaphylactic response. But, studies are revealing that they also play a significant role in immune activation, the development of autoimmunity, and increased inflammation.3

Unfortunately, mast cell disorders and mast cell activation syndrome (MCAS), in particular, are on the rise these days. I believe it’s in part because of the constant barrage of environmental toxins, molds, and chemicals. 

Let’s take a look at what exactly mast cell activation syndrome is, how it might be causing your mystery symptoms, and what you can do.


What is Mast Cell Activation Syndrome?

Mast cell activation syndrome is an immune disorder. It’s just one type of mast cell activation disease. 

What sets MCAS apart from other mast cell activation diseases is that it isn’t caused by an abnormally large amount of mast cells, and it isn’t a result of pathogen infection. Instead, when you have MCAS, you have a normal amount of mast cells, but they’re overactive and malfunctioning. 

When your body is exposed to what it thinks is a threat, these overactive mast cells start to go haywire and secrete massive amounts of chemical mediators stored in the cytoplasm of your cells—degranulation. What’s meant to be a positive, protective response from your mast cells instead triggers both local and systemic negative effects. 

When chemical messengers are released into your body, they set off an alarm that triggers an immune system response. And when this response becomes chronic—the chemical messengers are set off too much, too often—the result is mast cell activation syndrome.4


Mast Cell Activation Syndrome and Chemical Mediators

Mast cells are located near the border of just about every tissue in your body because they’re your first line of defense.

Mast cells are especially concentrated in your: 

Because of their close location just below the surface of your tissues, mast cells are readily available to defend against foreign invaders as soon as they enter your body.5

If your immune system is working as it’s designed, it’s able to fight off these foreign invaders effectively. We see problems arise when your immune system goes into a constant state of reaction to allergens. When this happens, your body becomes flooded with histamine and other chemical mediators released by mast cells in response to the allergen.

These mediators include:6

These chemical mediators are responsible for affecting early phases of allergic reactions. And once these chemical messengers are released into your system, they can trigger even more late-phase and systemic effects. 

When you have MCAS, you have repeated episodes of symptoms, although the organ systems that are affected and the combination of symptoms does vary. Let’s take a look at the variety of symptoms caused by overactive mast cells.


What Are the Symptoms of Overactive Mast Cells?

Symptoms associated with MCAS are caused by large amounts of histamine in your body when mast cells become hypersensitive and overactive. I’ve found that even with the huge variation of symptoms that can be present, the number one complaint from my patients with MCAS is often fatigue. 

Along with chronic fatigue, here’s a list of symptoms I most commonly see in my practice that cause me to suspect mast cell activation in my patients:7,8,9,10


What Diseases are Associated with Mast Cell Activation Syndrome?

A growing body of research reveals that mast cells play a key role in the early stages of many diseases. The list I give below is likely not all-inclusive but includes some of the ones that have been identified so far as being associated with MCAS:11,12,13,14,15,16,17


What Triggers Mast Cell Activation Syndrome?

Since 2007, when MCAS was officially recognized, our knowledge about the syndrome has increased significantly.18 But the reality is, even with this new data, we still have a lot of questions about MCAS.

One of them is: exactly what triggers the activation of mast cells and causes them to malfunction in the first place?

A severe flare-up of symptoms might be triggered by pollen in the spring, while a flare-up in the summer might be due to heat and increased exposure to sunlight. Unfortunately, we really can’t be sure exactly what the triggers are when it comes to MCAS. But, the good news is, even with these uncertainties, we do have a basic idea of potential triggers of mast cell activation. 

Let’s take a look at some of the triggers that can throw malfunctioning mast cells into overproduction mode:19,20

We know that overactive mast cells play a significant role in exacerbating autoimmunity. But the triggers that can cause mast cells to become hypersensitive are vast, as you can see above, and highly variable.


How is Mast Cell Activation Syndrome Diagnosed?

Diagnosing MCAS is difficult in part because we still don’t have a consensus for objective guidelines for a diagnosis. Despite a lack of consensus, a diagnosis of MCAS is sometimes given when a wide variety of signs and symptoms are present without a known trigger and other possible diagnoses have been ruled out. 

When a specific trigger can’t be identified and the mast cell activation doesn’t appear to have a known cause, it’s known as idiopathic.21

The first step I take with my patients is to determine if unexplainable symptoms like itching, flushing, gastrointestinal disturbances, systemic hypotension, and fluctuations in blood pressure are better explained by another diagnosis. The next step is to determine if these symptoms can be eliminated through routine treatment.

If symptoms aren’t eliminated, I’ll do a workup to see if there’s a known allergic basis for the symptoms. This allergic basis falls under two categories:

  1. Primary: activation of mast cells by mutations resulting in an abnormal amount of cells
  2. Secondary: external triggers like allergic antibodies or infection

If what’s going on doesn’t seem to fit in either the primary or secondary category, and if mast cells are found in a normal amount but are hyperresponsive, then I suspect mast cell activation syndrome.22

When I make a diagnosis of MCAS with my patients, I use this commonly accepted criteria. I look for two or more of the following:23

  1. Two or more organs that show symptoms of mast cell activation, such as wheezing, flushing, diarrhea, and hives.
  2. Two episodes with elevated levels of chemical mediators such as 11β-PGF2, serum tryptase, or 24-hour N-methylhistamine. 
  3. At least one episode with serum tryptase consistently greater than 15 ng/ml.
  4. Primary and secondary disorders, such as systemic mastocytosis or a clonal mast cell disease, have been ruled out with a negative bone marrow and tissue biopsy.

Although not necessarily a criteria for diagnosis, I consider the improvement of symptoms with drugs that target mast cell mediators as more evidence pointing to MCAS.24

Currently, we only know of a few biomarkers that implicate mast cell activation as the root cause of various symptoms and diseases. More research is needed to help us make a more definitive and accurate diagnosis.25 


How is Mast Cell Activation Syndrome Treated?

While mast cell activation syndrome isn’t curable, if you’ve been diagnosed with mast cell activation syndrome, you do have treatment options available to help you manage your symptoms.26

Because of the wide range of possible symptoms caused by mast cell activation syndrome, treatment will need to be tailored specifically to you and your symptoms. Thankfully, research studies on effective treatment options for sufferers of mast cell activation syndrome are ongoing.  

Antihistamines are typically the first course of treatment I recommend because they target the overwhelming amount of histamine produced by mast cells. I highly recommend Hist Assist to my patients. It’s a very effective antihistamine with a targeted blend of all-natural ingredients that create a powerful combination to promote optimal health and provide you with relief from mast cell activation syndrome symptoms.

For a more comprehensive course of treatment, here are three basic options to help manage your symptoms.


Three Basic Treatment Options 

We know that mast cell activation syndrome results from overactive mast cells. So, inhibiting and stabilizing them is an important step in managing your symptoms. There are three basic treatment options that are generally used:27,28,29

Inhibit the production of mediators through the use of:

Inhibit the release of mediators by stabilizing mast cells using:

Block the release of mediators through:

Beyond these basic therapy treatments, there are more options available that work by targeting specific symptoms caused by mast cell activation syndrome. For an in-depth look at more treatment options, I’ve listed several effective ones in my article 9 Proven Treatments for Mast Cell Activation Syndrome—Plus, a Surprising Newcomer.

I know that trying to figure out the best medications and supplements to treat your symptoms can be daunting. Not to mention, time-consuming. When you have a lot of options in front of you, it can be hard to know where to start and what’s best. To help reduce overwhelm, I recommend you take a look at your diet as an easy first step.

Becoming familiar with foods high in histamine, so you know what to avoid, is a natural place to start.  


High-Histamine Foods to Avoid

Mast cell activation syndrome can make you highly reactive to a wide variety of food. 30 So, avoiding foods that are high in histamine can help you identify foods you’re sensitive to. You might find that you’re able to consume some of the foods restricted on a low-histamine diet and tolerate them well. 

I suggest you use the following list as a general guideline and start by eliminating all of these foods in the beginning. Then, you can choose to add certain foods back into your diet. Always be sure to take note of how you feel when you’ve added a food back in, so you can recognize what, if any, symptoms reappear. Keeping a food journal is a great way to do this.

Here’s a list of the top high-histamine foods you’ll want to avoid:31

If you decide to add any food back into your diet, my recommendation is to continue avoiding, or at the very least limiting, all processed foods, artificial preservatives and sweeteners, sugar, dairy, wheat, and restricted spices. 

And, as an extra measure to help you control the amount of histamine you consume from food, I recommend Histamine Blocker to my patients. This patented supplement is formulated to help your body combat excessive histamine found in the food you eat.  


Where Do You Go From Here?

Mast cell activation syndrome is complicated because it can have both common and unusual symptoms that affect you on a multisystemic level. A doctor who’s familiar with this lesser known syndrome will help take the mystery out of what’s going on in your body. And, the information in this article is an excellent way for you to get started on your path toward healing. 

It’s important that you work with a doctor who’s familiar with mast cell activation syndrome and the various ways it shows up. 

If you have or suspect you have mast cell activation syndrome, you might feel overwhelmed and uncertain about what you can do to lessen your symptoms and improve your health. Know that most sufferers of mast cell activation syndrome are able to find an effective strategy that works for them and helps them feel significantly better. But, it will take patience, persistence, and an approach that’s made specifically for you and your symptoms. 

Now I want to hear from you. Do you suspect you have mast cell activation syndrome or have you already been diagnosed with mast cell activation syndrome? Have you found antihistamines like Hist Assist to be helpful in managing your symptoms?  Let me know in the comments! 


1 https://www.sciencedirect.com/science/article/pii/S0925443911000445

2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424662/  

3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597223/


5 https://www.sciencedaily.com/releases/2010/06/100607111308.htm

6 https://www.sciencedirect.com/science/article/pii/S0925443911000445

7 http://www.jillcarnahan.com/downloads/MCAS-Afrin.pdf

8 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753019/

9 https://www.aaaai.org/conditions-and-treatments/related-conditions/mcas

10 https://jhoonline.biomedcentral.com/articles/10.1186/1756-8722-4-10

11 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341697/

12 https://www.nature.com/articles/s41598-019-38679-4

13 https://www.ncbi.nlm.nih.gov/pubmed/25941080

14 https://www.ehlers-danlos.com/pdf/2017-Criteria-Nonexpert-PDFs/Mast-Cell-Disorders-in-EDS-Nonexpert-S.pdf

15 http://www.jillcarnahan.com/downloads/MCAS-Afrin.pdf

16 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888802/

17 http://www.dysautonomiainternational.org/blog/wordpress/a-tale-of-two-syndromes-pots-and-mcas/

18 http://www.jillcarnahan.com/downloads/MCAS-Afrin.pdf

19 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069946/

20 https://www.ncbi.nlm.nih.gov/pubmed/18680704

21 https://www.aaaai.org/conditions-and-treatments/related-conditions/mcas

22 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753019/

23 https://www.ncbi.nlm.nih.gov/pubmed/17537151

24 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753019/

25 https://www.jacionline.org/article/S0091-6749(18)30854-6/fulltext

26 http://www.jillcarnahan.com/downloads/MCASReview.pdf

27 http://www.jillcarnahan.com/downloads/MastCellActivationDxandTxMolderings.pdf

28 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903110/

29 http://www.jillcarnahan.com/downloads/MCAS-Afrin.pdf

30 http://www.jillcarnahan.com/downloads/MCAS-Afrin.pdf

31 https://histamine-sensitivity.com/histamine_joneja.html