MCAS 101: Understanding Mast Cell Activation Syndrome

Learn the symptoms, root causes, and functional medicine solutions for Mast Cell Activation Syndrome (MCAS). Discover natural ways to calm mast cells, reduce histamine, and support your body.

Yay me- post wedding and honeymoon I had a mouth infection that needed antibiotics – and it sent me into a mast cell flare! So- let’s talk about mast cells and MCAS. I do not personally have MCAS- but I do deal with mast cell activation like flares from my previous mold issue earlier this year! (black mold in my home for those that weren’t following my stories!) 

For an audio form of this blog you can listen to my podcast here

What Is Mast Cell Activation Syndrome (MCAS)?

Mast cells are a key part of our immune system, acting as first responders when the body detects invaders like bacteria, parasites, or allergens. I think of them like pac man in the body- trying to engulf and destory invaders!

These cells and “pac man” release chemical messengers—like histamine and cytokines—to help us fight off threats. But when mast cells become overactive or hypersensitive, they can go into overdrive, releasing too many mediators too often. That’s what we call Mast Cell Activation Syndrome (MCAS).

Since mast cells live all over the body—in the skin, gut, brain, lungs, and more—symptoms can be incredibly diverse, making MCAS tricky to pinpoint.

Why MCAS is So Misunderstood

There’s a lot of debate around what causes MCAS. While some practitioners attribute it to mold exposure or chronic infections like Lyme disease, I view it through a different lens. Often, MCAS arises when the body is under chronic stress and the nervous system is in survival mode. Instead of obsessively searching for a single root cause (which can lead to expensive testing and added stress), I focus on calming the system, building resilience, and going back to basics—especially for those who are sensitive to supplements and interventions. I focus on full body system healing and brain retraining WHILE addressing the potential root causes.

Common Symptoms of MCAS

Because mast cells affect multiple systems, symptoms can vary widely:

Skin:

Flushing

Hives or rashes

Swelling (especially in the face or lips)

Itching or raised welts

Gut:

Bloating

Nausea

Diarrhea

Reflux or abdominal pain

Heart & Blood Pressure:

Rapid heartbeat

Low blood pressure

Dizziness or fainting

Lungs & Airways:

Shortness of breath

Wheezing

Throat tightness

Nasal congestion or runny nose 

Neurological:

Headaches

Brain fog

Anxiety

Mood swings

Other:

Joint pain

Fatigue

Menstrual cramps

Root Causes & Triggers of MCAS

Everyone’s triggers are unique, but here are some common ones:

-Temperature extremes or weather changes

-Stress, lack of sleep, or sensory overload

-Environmental irritants (pollution, fragrances, EMFs, mold, etc.)

-High-histamine foods

-Certain medications (like NSAIDs or antibiotics)

-Physical exertion or injury

-Insect bites or stings

Some of the biggest root causes and triggers include:

• Mold toxicity (mycotoxins overstimulate mast cells)
• Lyme disease and co-infections (such as Bartonella, Babesia)
• Chronic viral infections (EBV, long-haul viruses)
• Environmental toxins (chemicals, heavy metals, fragrances)
• Gut dysbiosis & leaky gut (bacterial endotoxins trigger immune activation)
• Hormonal imbalances (estrogen dominance, thyroid issues)
• Stress and trauma (limbic system dysregulation worsens mast cell sensitivity)

In a one on one call- we can talk about identifying your personal triggers and building your own “flare toolkit” —it’s all about being prepared and empowered.

My triggers? Mold caused my mast cell responses. Now I get triggered with lack of sleep, stress, gut issues (hello antibiotics), medications (hello again antibiotics), and too much exercise. I also get slight flares sometimes when estrogen is highest in my luteal phase- but this only happens for me during a created flare not consistently (:

Functional Medicine Approach to MCAS

Instead of only suppressing symptoms, functional medicine looks at what’s driving mast cell over-activation. Key strategies include:

1. Identify & Remove Triggers

• Mold remediation and safe living environments
• Gut healing protocols to reduce dysbiosis and endotoxins
• Reducing environmental toxin exposure (air filters, clean beauty products)
• Evaluation of chrinic infections such as Lyme & Bartonella

2. Stabilize Mast Cells

• Quercetin – natural mast cell stabilizer and antioxidant
• Luteolin – calms neuroinflammation and mast cell activity
• Vitamin C – lowers histamine and stabilizes mast cells
• DAO enzyme – supports histamine breakdown
• Perilla– natural mast cell stabilizer

Nutrient deficiencies can amplify histamine reactions—especially when the essential cofactors needed for histamine breakdown are missing. Mast cells release histamine, but your body also has built-in pathways to break it down (DAO and HNMT enzymes). Without the right vitamins and minerals, those pathways stall, leaving histamine to build up and drive symptoms like flushing, itching, migraines, bloating, anxiety, or insomnia.

Key Nutrients That Keep Histamine in Balance:

• Vitamin C – helps degrade histamine, directly stabilizes mast cells
• Vitamin E – antioxidant that reduces oxidative stress, which otherwise worsens mast cell activation
• Vitamin B6 (P5P) – essential for DAO enzyme activity, key in histamine breakdown
• Folate + B12 + B2 (Riboflavin) – methyl donors that support the HNMT enzyme pathway to break down histamine inside cells
• SAM-e – direct methyl donor; enhances histamine clearance via HNMT
• Magnesium – calms nervous system excitability and supports DAO activity
• Copper – cofactor for DAO enzyme; low copper may impair histamine breakdown
• Zinc – regulates mast cell mediator release and supports antioxidant defenses

The Big Picture:
If these nutrients are depleted (from stress, poor diet, chronic illness, medications like PPIs, birth control, or metformin), histamine accumulates and mast cell reactivity worsens. This is why nutrient repletion is a core piece of any functional medicine approach to MCAS and histamine intolerance.

H1 and H2 medications to help block mast cells

The anti histamine medications below may be recommended by a physician to treat symptoms of mast cell activation or support MCAS during healing. These medications are meant to improve symptoms and provide supportive care and not to be used as a forever fix.

• H1 antihistamines: help with itching, abdominal pain, flushing, headaches, brain fog
• H2 antihistamines: help with gastrointestinal symptoms and overall mast cell stability (all mast cell activation symptoms)
• Mast cell stabilizers: help with stomach and intestinal symptoms and brain fog
• Leukotriene inhibitors: help with respiratory symptoms and overall mast cell stability (all mast cell activation symptoms)
• Aspirin therapy (under direct supervision of a physician): if tolerated and if prostaglandins are elevated, helps with flushing, brain fog and bone pain

Table 1. Some First Generation H1 Antihistamines

Brand Name	Generic Name
Atarax®	Hydroxyzine hydrochloride
Benadryl®	Diphenhydramine
Chlortrimeton®	Chlorpheniramine
Doxepin®, Sinequan®	Doxepin hydrochloride
Tavist®	Clemastine

Table 2. Some Second Generation H1 Antihistamines (may tend to cause less drowsiness)

Brand Name	Generic Name
Allegra®	Fexofenadine
Claritin®	Loratidine
Clarinex®	Desloratidine
Zaditor®/Zaditen® (in Europe)*	Ketotifen
Xyzal®	Levocetirizine
Zyrtec®	Cetirizine

Table 3. Some H2 Antihistamines

Brand Name	Generic Name
Axid®	Nizatidine
Pepcid®	Famotidine
Tagament®	Cimetidine

---

Table 4. Some Leukotriene Inhibitors

Brand Name	Generic Name
Singulair®	Montelukast
Accolate®	Zafirlukast
Zyflo®/Zyflo CR®	Zileuton

Table 5. Mast Cell Stabilizers

Brand Name	Generic Name
Gastrocrom®	Oral cromolyn sodium
Zaditor®/Zaditen® (in Europe)*	Ketotifen
Algonot, Neuroprotect, etc.	Food supplements containing bioflavonoids such as quercetin and luteolin
Bayer aspirin; Aspirin; ASA	Aspirin, acetylsalicylic acid (for those with high prostaglandin levels; aspirin therapy must be initiated under the direct supervision of a physician!)

3. Support Gut & Immune Health

The gut is the frontline of the immune system, and for those with MCAS, it’s often a key driver of histamine overload and chronic inflammation. A leaky, inflamed gut lining can allow bacterial endotoxins (LPS) and food particles to enter circulation, stimulating mast cells and worsening reactivity. Restoring gut integrity and balancing the microbiome is essential for calming mast cell activation.

• Digestive enzymes – support proper protein breakdown, reducing undigested food particles that could trigger immune reactions. For MCAS, I often recommend broad-spectrum enzymes combined with ox bile (if bile flow is sluggish) to improve fat absorption.
• Probiotics (strain-specific, low histamine) – not all probiotics are safe for MCAS. Avoid histamine-producing strains like Lactobacillus casei or bulgaricus, and instead focus on histamine-degrading or neutral strains such as Bifidobacterium infantis, Bifidobacterium breve, Lactobacillus plantarum, and Lactobacillus rhamnosus GG. These can support barrier integrity and immune balance without flaring symptoms.

Note with mold and lyme- these are both BIG MCAS triggers. I have seperate posts all about there! Learn about mold toxicity and MCAS here. Learn about lyme and MCAS here.

Gut Lining Repair & Immune Modulation:

• L-glutamine – primary fuel for enterocytes (gut lining cells), reduces permeability.
• Colostrum or IgG immunoglobulins – bind bacterial toxins and calm gut-driven immune activation. SBI Protect (serum-derived immunoglobulins) is one of my favorite tools here.
• Zinc carnosine – clinically shown to promote mucosal healing and reduce inflammation in the GI tract.
• N-acetyl glucosamine (NAG) – supports mucin production and tight junctions, helping seal “leaky gut.”
• Aloe vera & DGL (deglycyrrhizinated licorice) – soothe mucosal irritation and reduce inflammation.
• Addressing Overgrowths & Pathogens:
• When stool or OAT testing reveals dysbiosis or infections, targeted antimicrobials are critical. Herbs I often use in rotation include:
• Berberine – broad antimicrobial, also improves blood sugar regulation.
• Oregano oil – potent antifungal/antibacterial, though best in short courses due to potency.
• Neem – excellent for bacterial overgrowth and parasites.
• Artemisia (wormwood) – used for parasitic infections and protozoa.
• Caprylic acid & undecylenic acid – antifungal support against Candida.

4. Regulate the Nervous System

• Breathwork, meditation, and limbic retraining programs (DNRS, Gupta, Primal Trust)
• Gentle exercise to improve circulation and reduce inflammation- too much can stimulate mast cells too much
• Sleep hygiene to calm histamine surges at night
• Gentle sweating and sauna work if tolerated

If this resonates with you or someone you love, I highly recommend forwarding it to them! As always- reach out to me if you need one on one help!

FAQs About Mast Cell Activation Syndrome

Q1: Is MCAS the same as histamine intolerance?
Not exactly. Histamine intolerance is primarily due to an imbalance between histamine intake/production and the body’s ability to break it down (DAO enzyme activity). MCAS involves mast cells releasing multiple mediators, not just histamine. MCAS think multiple body systems affected vs just slow breakdown of histamine.

Q2: How do doctors diagnose MCAS?
Diagnosis can be challenging. Common labs include tryptase, histamine, prostaglandins, and chromogranin A. Functional medicine practitioners often look at symptom patterns and triggers alongside lab testing.

Q3: Can MCAS be cured?
There is no quick cure, but addressing root causes—like mold, infections, gut health, and toxins—alongside mast cell stabilizers can dramatically improve quality of life.

Q4: What diet helps with MCAS?
Many clients benefit from a low-histamine, anti-inflammatory diet that removes alcohol, aged cheeses, processed foods, and high-histamine leftovers. With MCAS I typically recommend a gluten free, dairy free, low histamine diet. Some need further adjustments!

MCAS can feel overwhelming, but with the right tools, you can calm mast cells, identify your root causes, and regain quality of life.

If you’re struggling with symptoms of MCAS, mold toxicity, or histamine intolerance, you don’t have to do it alone.

👉 Click here to schedule a consultation with me

Together, we’ll find the root causes behind your MCAS and create a step-by-step healing plan tailored to you.

With Love,
Lacey Dunn Holland, MS, RD, LD, CPT

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