What do migraines, skin rashes, and digestive issues all have in common? They can all be triggered by a complex condition known as mast cell activation syndrome – a tricky imbalance that causes some of your immune cells to begin malfunctioning.

Getting to the root cause of this perplexing condition and its troubling symptoms can be tricky. But more and more research is finding that the underlying trigger may be a stealthy culprit that could be lurking within your home – quietly wreaking havoc on your health unbeknownst to you.

This stealthy culprit I’m referring to is toxic mold. Today we’re going to dive into the nitty-gritty details of exactly what mast cell activation syndrome is, how mold can trigger your mast cells to begin misbehaving, how this complex condition is diagnosed, and most importantly – what you can do about it.

What Exactly Are Mast Cells?

Mast cells are specialized immune cells that serve as sentinels for your immune system – essentially “sounding the alarm” when a threat is detected. When your mast cells perceive a threat, they discharge and distribute a cascade of pro-inflammatory signaling molecules in a process known as degranulation.

In a healthy balanced immune system, the process goes something like this:¹

• Your mast cells degranulate – releasing a cocktail of inflammation-stoking signaling molecules.
• These molecules spread throughout your body and activate your immune system – revving up inflammation and preparing your body to launch an attack against the foreign invader.
• Your immune system identifies, neutralizes, and eliminates the threat.
• Your immune system recognizes that the threat has been neutralized and begins returning to homeostasis – down-regulating inflammation and sending your immune cells back into “standby” mode.

But in some cases, your mast cells can begin malfunctioning – throwing this whole process out of whack and creating a whole slew of troubles for your health.

Mast Cell Activation Syndrome Versus Mastocytosis: What’s the Difference?

There are a couple of distinct ways your mast cells can potentially begin malfunctioning – and it’s important to know the difference. Let’s take a look at the differences between the two primary mast cell-mediated imbalances:^2,3

• Mastocytosis: With mastocytosis, there is a proliferation or growth of mast cells that can begin accumulating in organs and spreading through your body, almost like a cancer. Mastocytosis is quite rare and is not usually triggered by any environmental irritant.
• Mast cell activation syndrome: In mast cell activation syndrome, also known as MCAS, you have a normal amount of mast cells floating around within your body. But these mast cells are overactive and aggressive – meaning even the slightest irritant can cause them to become highly aggravated and immediately release their store of pro-inflammatory mediators.

So as the name implies, mast cell activation syndrome is a condition in which your mast cells become overactivated – causing them to have a heightened and dramatic response to anything it identifies as a potential threat. But before we dive into the symptoms associated with MCAS, it’s important to differentiate it from another complex condition that it’s often confused with – histamine intolerance.

What About Histamine? Is Histamine Intolerance the Same As Mast Cell Activation Syndrome?

Histamine intolerance is a condition characterized by an accumulation of a compound known as histamine within the body – either due to increased histamine availability or impaired histamine degradation.⁴ Because mast cells are some of the primary producers of histamine, it has been widely assumed that histamine intolerance and MCAS simply go hand in hand. But is histamine intolerance really the same thing as MCAS?

The answer to that question is – it’s complicated. You see, MCAS can certainly be a major contributing factor when it comes to histamine intolerance. But true mast cell activation is much more complicated than that and the histamine released during mast cell degranulation is just a small part of the story. That’s because when mast cells degranulate, they release a whole host of chemical mediators, including:^5,6

• Histamine
• Cytokines
• Interleukins
• Prostaglandins
• Chemokines

And the release of each of these pro-inflammatory mediators has a distinct impact on your body. This combination of effects triggered by each of these specific signaling molecules is what creates the constellation of symptoms seen in MCAS.

So, What Are the Symptoms of Mast Cell Activation Syndrome (MCAS)?

Inflammation is a natural protective and healing mechanism your body initiates in response to a threat. But if this inflammatory process goes overboard or extends for too long without resolution, it can trigger a wide constellation of symptoms that can impact just about every inch of your body from the inside out. Some of the most common symptoms associated with the overzealous influx of pro-inflammatory mediators triggered by MCAS include:^7,8

• Fatigue
• Poor memory
• Brain fog
• Inability to focus
• Mood disorders
• Migraines
• Rashes
• Hives
• Low blood pressure
• Heart racing
• Becomes lightheaded when you stand up quickly
• Diarrhea
• Abdominal pain
• Constipation
• Nausea
• Bloating
• Strong PMS symptoms
• Allergy-like symptoms
• Asthma
• Wheezing
• Shortness of breath

So, what on earth can cause your mast cells to begin malfunctioning to the point that you develop these symptoms seen in mast cell activation syndrome?

What Causes Mast Cell Activation Syndrome?

MCAS can potentially be triggered by any number of exposures that can essentially overload your immune system and cause your mast cells to go a little haywire. Some of the more common underlying causes include elevated or prolonged exposure to:

• Chemicals
• Allergens
• Viruses
• Heavy metals
• Toxins
• Hidden infections

But there’s another potent trigger that is often the most problematic when it comes to MCAS – toxic mold.

Can Mold Toxicity Cause Mast Cell Activation Syndrome (MCAS)?

The answer to this question is – yes, absolutely! You see, while mold is a natural part of our environment, toxic mold can grow inconspicuously in many homes and buildings – exposing you to unhealthy levels of these stealthy fungi. As these toxic mold strains release their spores, you inevitably come into contact with them.

As these spores make their way into your body and release their microscopic poisons your immune system becomes activated – triggering massive mast cell degranulation. With repeated exposure, this mast cell degranulation triggered by toxic fungi can lead to an increase in levels of a pro-inflammatory mediator known as Prostaglandin D2 or PGD2. An increase in PGD2 levels can create a vicious cycle – triggering mast cell hypersensitivity which leads to increased degranulation, which further ups PGD2 levels, and so on and so forth.⁹

This cascade of inflammation and mast cell degranulation triggered by mold can send your mast cells into a tailspin – causing them to be chronically stuck in overproduction mode. So how exactly do you identify these misbehaving mast cells as the root of your symptoms and arrive at a diagnosis of MCAS?

So, How Do You Get Diagnosed With Mast Cell Activation Syndrome? 

Mast cell activation can be somewhat tricky to diagnose. Part of the reason MCAS can be tricky to diagnose is because it’s triggered by overactive mast cells, not an overabundance of mast cells – meaning lab tests often come up normal.

So, unfortunately, when it comes to inherently complex conditions like MCAS, diagnosis becomes a process of elimination. Arriving at a diagnosis of MCAS requires time and detective work – systematically ruling out other potential diagnoses until a conclusion of MCAS is reached.

With that being said, there are a couple of strategies that can help us potentially arrive at a diagnosis of MCAS more quickly:

Biomarkers for Chronic Inflammatory Response Syndrome

Though there is no definitive test for MCAS there are numerous tests you can combine to support your diagnosis. When it comes to MCAS that’s triggered by mold, there are a few biomarkers that are more common than others which are:

• Matrix metalloproteinase-9 (MMP-9)
• Complement C4a (C4b is usually seen with bacterial triggers)
• Transforming growth factor beta (TGF-β)
• Vascular endothelial growth factor (VEGF)

There are a couple of important points to keep in mind when it comes to these biomarkers and lab testing in general:

• You may have to request lab work from multiple labs. Because these are more obscure lab tests, not all labs are capable of performing all of them.
• It’s important to ensure both your doctor and the lab know how to carefully handle samples for accurate results – as inappropriate handling and testing can skew results and provide an inaccurate picture. This is why I highly recommend partnering with an experienced Integrative and Functional Medicine Doctor if you’re concerned about MCAS.
• Ultimately, blood tests can’t really confirm or deny the presence of an illness, they can simply help provide more clues to the inflammation going on below the surface.

MCAS Diagnosis Consensus-2

The updated version of diagnostic criteria has been dubbed consensus-2 and includes the following guidelines for MCAS diagnosis:⁵

Typical clinical signs: Consensus-2 has a slightly altered description of clinical signs to include the presence of severe, recurrent episodes of systemic mast cell activation. Systemic is defined as including a minimum of two distinct organ systems and may include:

• Urticaria
• Flushing
• Pruritus
• Angioedema
• Nasal congestion
• Nasal pruritus
• Wheezing
• Throat swelling
• Hoarseness
• Headache
• Hypotensive syncope
• Tachycardia
• Abdominal cramping
• Diarrhea

Biochemical markers: Consensus-2 also includes a 20% plus 2 ng/ml increase in serum tryptase level from the individual’s baseline but extends to additional biochemical markers as well. Additional mast cell-derived biochemical markers that can be used for diagnosis include:

• Histamine
• Histamine metabolites
• PGD₂ metabolites
• Heparin

Symptoms improvement: Consensus-2 also includes a measurable response and improvement of symptoms when administered the following drug therapies:

• Mast cell-stabilizing agents
• Drugs directed against mast cell mediator production
• Drugs blocking mediator release or effects of mast cell-derived mediators

Having broader and more robust diagnostic guidelines as seen in the updated consensus-2 criteria allows us to more accurately diagnose patients. And with increased diagnostic capabilities, we can better address symptoms and get patients on a path to management and healing.

MTHFR Status and MCAS

MTHFR stands for methylenetetrahydrofolate reductase and is an essential enzyme that’s necessary for a process known as methylation. Methylation is a complex process that your body uses to process, metabolize, and convert certain compounds and nutrients into different forms – either to be better utilized by the body or broken down for elimination. And one of the most important pathways your body uses to break down histamine – one of the pro-inflammatory mediators secreted by mast cells – is methylation.

Some people have a mutation in the genes that control how their body methylates – impairing their ability to properly break down histamine as well impeding their ability to properly activate and utilize crucial nutrients. To learn more about MTHFR mutation and excess histamine, head over and check out the following articles:

• MTHFR Gene Mutation: How to Know If You Have It and What to Do
• What’s the Big Deal About Methylation?! Update of the Popular MTHFR Blog Post…
• Boost Your DAO Levels to Fight Histamine

Testing MTHFR status and assessing for this genetic mutation can help create a clearer picture of whether or not you may be dealing with MCAS. So you’re probably wondering what happens once a diagnosis of MCAS is reached and what kind of treatment options there are.

What Is the Best Treatment for Mast Cell Activation Syndrome?

Treating MCAS requires a big-picture approach that addresses multiple factors. Here’s what I recommend:

Address Mold Exposure:When it comes to treating MCAS that’s been triggered by mold, reducing mold exposure is the name of the game. Without identifying and addressing mold exposure, symptoms will only continue to get worse and treatments will be ineffective. To learn how you can begin addressing mold exposure and eliminating mold growth from your home, head over and check out the following resources:

• Got Mold? Prevent Mold by Healing Your Home’s Microbiome
• How to Get Rid of Mold – Definitive Mold Removal Guide
• Mycotoxins: The Hidden Danger Lurking In Your Kitchen
• The Low Mold Diet: What It Is and How to Follow It

Addressing mold exposure is foundational – you simply can’t begin treating mold-mediated MCAS without removing mold from the equation.

Minimize Your Toxic Burden: While mold can be a major trigger of MCAS, it’s not the only toxic compound that can contribute to and exacerbate these malfunctioning mast cells. It’s important to address your overall toxic burden and take steps to minimize your exposure to toxins from all sources. To get started on minimizing your toxic burden, check out my article What is Your Total Toxic Burden? How To Reduce It For Better Health.

Incorporate MCAS-Stabilizing Supplements: There are a number of supplements you can take to help MCAS. These include natural antihistamines and mast cell stabilizers such as:

• Ascorbic acid and Vitamin C
• Diamine Oxidase enzymes (DAO)
• Glutathione
• Methyl Boost
• Omega-3 fatty acids
• Pyridoxal 5-Phosphate (P5P)
• Probiotics that contain Bifidobacterium and Lactobacillus
• Quercetin
• Resveratrol
• Turmeric
• B Vitamins – especially B6 and B12

Supporting your body with these natural supplements can help soothe your over-sensitive mast cells and help restore balance to your body.

Partner With a Specialist: Treating MCAS can be tricky and often requires a significant level of personalization as well as some trial-and-error to figure out what works best for you. So if you’ve been diagnosed with MCAS or suspect you may be struggling with symptoms of MCAS, I cannot overemphasize the importance of working with an experienced Integrative and Functional Medicine Practitioner.

Unfortunately, many conventional medical doctors have a poor or nonexistent understanding of the complexities of MCAS. So it’s crucial to partner with a practitioner who will help you get to the root cause of your symptoms and help create a comprehensive and customized plan for helping you heal. To dive deeper into some of the diagnostic criteria and treatment protocols a Functional Medicine Doctor may implement in MCAS, check out my article Mast Cell Activation Syndrome: How It’s Diagnosed and 2 Exciting New Treatments.

My Personal Experience with Mold and Mast Cells

I know firsthand how scary, perplexing, and frustrating mold toxicity and mast cell activation syndrome can be. You see, in 2014 my office flooded and this triggered massive mold growth that we were unfortunately unaware of for several months. As soon as I realized I’d been exposed to toxic levels of mold for months, I immediately removed myself from the exposure and started implementing a detox and healing protocol.

As my body began to detox, I experienced brain fog, respiratory issues, gastrointestinal distress, and my skin was covered in hives. I quickly realized that as my body began to release and process out the toxic mold within my body, it triggered a massive mast cell activation.

Even with my extensive knowledge and experience as a functional medicine doctor, experiencing these perplexing symptoms was downright frightening. All that to say, if you’re struggling with MCAS, the emotions you’re feeling are normal and you don’t have to go at this alone.

Are You Concerned About MCAS?

The truth is, working to get a chronic condition like MCAS under control can take time, patience, and a lot of faith. But the good news is, with the right protocol and some consistency, it is absolutely possible to live a full and healthy life with MCAS. If you have any suspicion that you may be struggling with the symptoms of MCAS, I cannot overemphasize the importance of seeking out the guidance of a functional medicine practitioner as soon as possible – the steady guidance and support of an experienced practitioner are truly invaluable.

Resources

1. Mast Cell Activation Syndrome: A Primer for the Gastroenterologist – PubMed (nih.gov)
2. Mastocytosis and Mast Cell Activation Disorders: Clearing the Air (nih.gov)
3. Spectrum of mast cell activation disorders – PubMed (nih.gov)
4. Histamine and histamine intolerance | The American Journal of Clinical Nutrition | Oxford Academic (oup.com)
5. Mast cell activation syndrome: a review – PubMed (nih.gov)
6. Mast Cell Activation Syndrome: Proposed Diagnostic Criteria (nih.gov)
7. Diagnosis of mast cell activation syndrome: a global “consensus-2” (degruyter.com)Diagnosis of mast cell activation syndrome: a global “consensus-2” (degruyter.com)
8. Mast Cell Activation Syndrome: Proposed Diagnostic Criteria (nih.gov)
9. Impact of mold on mast cell-cytokine immune response – PubMed (nih.gov)

* These statements have not been evaluated by the Food and Drug Administration. The product mentioned in this article are not intended to diagnose, treat, cure, or prevent any disease.   The information in this article is not intended to replace any recommendations or relationship with your physician.  Please review references sited at end of article for scientific support of any claims made.

Published June 29, 2024