All About Mast Cell Activation Syndrome: What Is It and How to Treat It

If you are suffering from a strange array of symptoms that traditional medicine can't explain, mast cell activation syndrome may be to blame. Symptoms of this disorder can include skin rashes, headaches, fatigue, digestive issues, and more. However treating MCAS with a functional medicine approach can help get to the root of the problem and provide relief from these often debilitating symptoms.

Let's learn what MCAS is, how it's diagnosed, and treatment options using a functional medicine approach.

What is mast cell activation syndrome?

Mast cell activation syndrome (MCAS), is a chronic disorder caused by the overactive response from a group of specialized immune cells known as mast cells. Mast cells are a type of danger signal for the immune system. They store inflammatory defense compounds, including histamine, which is the all-too-well-known culprit behind allergic reactions. 

When a mast cell detects a harmful invader, they signal the release of pro-inflammatory molecules, including histamine, that tell the immune system it’s time to fight back (1).

In a healthy reaction, mast cells trigger an inflammatory response, the immune system springs into action to defend the body, and then your immune system tamps down the inflammation to return to a normal baseline—the threat now resolved.

But with MCAS, mast cells begin to malfunction. Instead of turning off after they’ve done their job, they keep releasing proinflammatory signals. What’s meant to be a protective response from your mast cells instead triggers distressing local and systemic symptoms.

Related: Warning Signs for Chronic Inflammationauto

Symptoms of mast cell activation syndrome

Because mast cells are designed to protect the body, they are located in higher concentration in critical areas that most frequently come into contact with the environment—in airways, intestines, and skin (2). Because of this, mast cell disorders often cause symptoms in the skin, gut, or respiratory system (3).

  • Skin-related symptoms of mast cell disorders: Itching, swelling, and/or flushing (with or without a rash)
  • Gastrointestinal symptoms: Nausea, vomiting, diarrhea, abdominal pain, reflux, or bloating
  • Cardiovascular symptoms: Changes in blood pressure or heart rate
  • Respiratory-related symptoms: Shortness of breath, coughing, itchy throat, and/or asthma-like symptoms
  • Brain and mental health symptoms: Brain fog, fatigue, headaches, difficulty concentrating, bone/muscle pain.

Similar to other immune-related diseases (autoimmunity, etc.) MCAS often causes flare ups triggered by stress, illness, or other stimuli, followed by a period of regularity. One of the hallmark signs of MCAS is a cyclical waxing and waning of symptoms with varying degrees of severity depending on what exactly triggers overactive mast cell activity (4). 

What triggers MCAS flare up?

MCAS occurs in response to anything that your body thinks is a threat—whether it really is or not. What triggers MCAS symptoms varies from one person to another, and they may change over time. Some of the identifiable triggers of MCAS include (5):

  • Heat, cold or sudden temperature changes
  • Stress: emotional, physical, including pain, or environmental (i.e., weather changes, pollution, pollen, pet dander, etc.)
  • Exercise
  • Fatigue
  • Drugs (opioids, NSAIDs, antibiotics and some local anesthetics) and contrast dyes
  • Natural odors, chemical odors, perfumes and scents
  • Venoms (bee, wasp, spiders, fire ants, jellyfish, snakes, biting insects, such as flies, mosquitos and fleas, etc.)
  • Infections (viral, bacterial or fungal)
  • Irritation on the skin, friction, or vibration
  • Sun/sunlight

Hormonal changes, especially estrogen fluctuations may also influence mast cell activity (6). 

High histamine foods and beverages include fermented foods, alcohol, aged meat and cheese, nuts, and certain fruits & vegetables.

Related: Hidden Triggers of Autoimmune Disease

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Causes of Mast Cell Activation Syndrome

Mast cell activation syndrome is an immune disorder, caused by immune dysfunction. There are other types of mast cell activation disease that are caused by an abnormally high number of mast cells or as a result of infection.

However, MCAS involves the dysfunction or hyperactivity of an otherwise normal number of mast cells.

Environmental toxins may provoke mast cells

A high toxic load could potentially cause mast cell dysfunction, causing the release of histamine and other inflammatory mediators.

In one study, more than half of those with MCAS also fit criteria for chemical intolerance (CI). Essentially, as your immune system is exposed to environmental toxins either during a one-time acute event, a series of exposures, or long-term, low-level exposures, tolerance decreases until mast cells begin to malfunction (7). As a result, some people experience systemic symptoms and persistent intolerances to chemicals—and often foods and drugs—which never bothered them before and do not bother most people.

Read: The Benefits of Quercetin & Other Natural Antihistamines


Infections can both be a trigger for symptom flare up, but also the underlying root cause of MCAS. Sometimes a severe, chronic, or underlying infection (known as a latent infection) can essentially trick your immune system to remain hypervigilant and cause decreased function of natural killer cells, increased systemic inflammation, and overall immune system dysfunction (8,9). 

Life-threatening Covid infections have one thing in common with MCAS—a massive release and accumulation of inflammatory cytokines and immune dysfunction. 

Read more: Long Covid Influenced by Gut Microbiome

Methylation & MCAS

MTHFR stands for methylenetetrahydrofolate reductase and it’s an essential enzyme that’s key for the body-wide process known as methylation. Methylation drives the metabolism of compounds and nutrients, changing them into different forms either to be used by the body, or to be properly eliminated. Converting synthetic folic acid to the bioavailable methyl-folate is one example. 

Methylation also breaks down histamine and other pro-inflammatory signaling molecules released by mast cells. Genetic changes can impair the methylation process, possibly also restricting the ability to break down histamine as well.

Read: Half the Population Has This Genetic Mutation—Here’s What It Means for Your Health

Treating MCAS with functional medicine

Treating MCAS requires a comprehensive, tailored approach. This includes identifying any underlying triggers or root causes, as well as supporting the body’s natural ability to regulate inflammation and histamine.

Functional medicine practitioners may recommend various therapies to stabilize mast cells, including:

  • Dietary changes to reduce your intake of histamine-rich foods 
  • Antihistamines or mast cell stabilizing nutraceuticals
  • Optimization of detox pathways to reduce toxic triggers
  • Sleep, stress, and exercise recommendations

Working with an integrative medicine team is key to stabilizing your immune response if you’re experiencing symptoms of MCAS.

Navigating a chronic illness like MCAS can feel frustrating, lonely, intimidating. But with a functional medicine team in your corner, you’ll be on the road to recovery. Together, we’ll develop the right strategies to stabilize overactive mast cells and restore immune balance.




Antibiotics, autoimmune disease, Holistic Medicine

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