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TL;DR: I reduced my MCAS symptoms—itching, hives, flushing and more—by following a comprehensive “MCAS kitchen sink protocol” combining antihistamines, mast cell stabilizers, and supplements. This post breaks down what I used and how it helped me reclaim my life.

Living with mast cell activation syndrome (MCAS) can feel like fighting an invisible enemy. If you’re like me, you know how unpredictable and exhausting MCAS can be—flushing, itching, hives, headaches, nausea, fatigue, brain fog. It’s a condition where mast cells release inflammatory chemicals in response to common triggers like food, stress, hormones, or even mild infections.

For years, I felt like I was just reacting to symptoms. MCAS treatment felt impossible to personalize, and no single intervention gave lasting relief. That’s when I came across the idea of a “kitchen sink protocol” for MCAS—a layered approach using different types of medications, supplements, and lifestyle tools that work together to calm the immune system.

After trial and error—and close work with my immunologist and LLMD—I created a customized protocol that transformed my life. This post shares everything I learned: what I took, how I felt, and tips for building your own version of the protocol in partnership with your doctor.

What Is MCAS (Mast Cell Activation Syndrome)?

Mast Cell Activation Syndrome (MCAS) is a complex and often misunderstood condition where the body’s mast cells release an overload of chemical mediators—like histamine, prostaglandins, and cytokines—causing widespread inflammation and unpredictable symptoms.

Unlike classic allergies, which usually have a clear trigger and reaction pattern, MCAS symptoms can vary daily and affect multiple systems, including:

• Skin: itching, rashes, hives, flushing
• Digestive tract: nausea, abdominal pain, diarrhea
• Nervous system: brain fog, migraines, anxiety
• Cardiovascular system: lightheadedness, rapid heart rate
• Musculoskeletal system: fatigue, joint pain

Triggers can include:

• Foods (especially high-histamine or fermented items)
• Stress and strong emotions
• Temperature changes
• Infections or viruses (like COVID-19)
• Hormonal shifts
• Chemical exposures (like perfumes or cleaning agents)

MCAS is commonly seen in people with conditions like Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Long COVID, POTS, Ehlers-Danlos Syndrome (EDS), and mold illness. Diagnosing it can be tricky, and many people go years without answers.

My Struggles with Chronic MCAS Symptoms

Before I found a way to manage my MCAS, my life was ruled by symptoms I didn’t fully understand. Some days, it felt like my body was in a constant state of emergency. I experienced chronic itching, flushing, palpitations, frequency, rashes, low grade fevers, sore throat, headaches, nausea, brain fog, swelling, reflux, diarrhea and fatigue, even when I avoided obvious triggers.

I tried all the usual treatments: rotating antihistamines, dietary changes, topical creams, and even prescription meds. But nothing seemed to bring lasting relief. I’d have short stretches of improvement, followed by major flares that left me completely wiped out.

The hardest part was the unpredictability. A food I tolerated yesterday would cause hives today. A light walk would trigger asthma and leave me bedbound for days. Managing MCAS felt like chasing a moving target, and I started to lose hope that I’d ever feel normal again.

Worse still, these symptoms didn’t exist in isolation. I live with ME/CFS, and my MCAS flare-ups often amplified the fatigue, post-exertional malaise (PEM), and brain fog I was already managing. Every day was a puzzle: What caused this flare? What can I even do about it?

That all began to shift in 2021, when I decided to take a more layered and aggressive approach. That’s when I started building what I now call my “MCAS Kitchen Sink Protocol.”

What Is the MCAS Kitchen Sink Protocol?

When it comes to treating MCAS, there’s rarely a one-size-fits-all solution. For me, the turning point came when I stopped waiting for a single magic fix and began combining multiple tools to calm my overactive immune system.

This layered approach—what my doctors referred to as throwing the kitchen sink is the MCAS Kitchen Sink Protocol—targets different aspects of mast cell activation, histamine release, and systemic inflammation. It’s designed to block mediators, prevent flares, and support the body through MCAS-specific supplements, medications, and natural compounds.

I built this protocol with the help of my immunologist and Lyme-literate doctor (LLMD), tailoring it over time based on what worked and what didn’t. Here’s a breakdown of the four core “stacks” I used:

Stack 1: Antihistamines for MCAS Relief

Antihistamines are the frontline defense against histamine overload, a major cause of MCAS symptoms like rashes, itching, flushing, and digestive upset.

There are two primary types:

• H1 blockers – Target symptoms like itching and skin irritation
  • Examples: cetirizine (Zyrtec), loratadine (Claritin), diphenhydramine (Benadryl)
• H2 blockers – Help with GI-related symptoms like nausea, reflux, and stomach pain
  • Examples: famotidine (Pepcid), ranitidine (Zantac, discontinued in some areas)

Most people need both H1 and H2 blockers to get full coverage.

Stack 2: Mast Cell Stabilizers

These treatments calm mast cells and reduce their likelihood of releasing inflammatory mediators. They’re especially useful when you’re highly sensitive or experiencing daily flares.

• Cromolyn sodium (Gastrocrom) – Oral mast cell stabilizer often taken before meals
• Ketotifen – A prescription antihistamine with mast cell stabilizing properties

These agents work more proactively than reactively, helping stabilize your baseline over time.

Stack 3: Supplements for MCAS Support

This stack includes compounds with natural anti-inflammatory, antioxidant, or mast cell stabilizing effects. While supplements aren’t a replacement for medication, they’re often critical support tools.

Some that helped me:

• Quercetin – A bioflavonoid that inhibits histamine release
• Luteolin – Antioxidant with neuroprotective effects
• Magnesium glycinate – Helps calm the nervous system and supports better sleep and muscle function.
• PEA (Palmitoylethanolamide) – For neuroinflammation and pain regulation.
• DAO Enzyme – Taken before meals to reduce food-triggered histamine responses.
• Vitamin C – Histamine-lowering and immune-supporting
• Vitamin D – Regulates immune function and inflammation
• Resveratrol – Antioxidant with mast cell modulating potential

Always check for filler sensitivities and start slow—some MCAS patients react even to “hypoallergenic” formulas.

Stack 4: Other Helpful Agents

These are extra tools I layered in to manage symptoms and improve quality of life, depending on what I needed most.

Examples include:

• Low-Dose Naltrexone (LDN) – Helps modulate immune activity
• Chinese Skullcap (tea or extract) – Herbal support with anti-inflammatory effects
• Aimovig – A CGRP inhibitor I used for related migraine symptoms
• Xolair –  a monoclonal antibody that reduces the sensitivity of mast cells to allergens and other triggers

This category is flexible. It can also include antimicrobials (if MCAS is triggered by infections), mold binders, or gut health supports depending on your case.

Customizing the Protocol

There’s no exact formula. What helped me was introducing one stack at a time, monitoring symptoms, and slowly layering in the rest.

Your ideal stack might look different based on your triggers, comorbid conditions, and medication access. But the idea is the same: hit MCAS from multiple angles, not just one.

How I Used the Kitchen Sink Protocol to Calm My MCAS

I started using the Kitchen Sink Protocol in 2021, shortly after a COVID reinfection made my already-bad MCAS symptoms spiral out of control. Every day felt like survival mode—flaring skin, relentless itching, crushing fatigue, and intense brain fog. I needed a reset, fast.

That’s when I committed to a structured, multi-pronged MCAS program treatment plan. Here’s what I did:

My Personal MCAS Protocol

• Stack 1 (Antihistamines):
  I took cetirizine (10 mg) and famotidine (20 mg) twice daily—morning and evening. This helped calm my histamine-driven symptoms like itching, flushing, reflux, and post-meal flares.
• Stack 2 (Mast Cell Stabilizers):
  I used cromolyn sodium (200 mg) before every meal and snack, and added ketotifen (3 mg) three times daily. These gave me much-needed stability by reducing my daily flare frequency.
• Stack 3 (Supplements):
  I took quercetin (500 mg), vitamin C (1000 mg), and luteolin twice daily. Over time, these helped lower background inflammation and supported a more stable baseline. I also took DAO Enzyme (Diamine Oxidase) before meals which helps break down dietary histamine.
• Stack 4 (Other Agents):
  I added Aimovig every four weeks for migraines, low-dose naltrexone (4.5 mg) daily to help regulate immune overactivation, and drank herbal tea with Chinese skullcap for its calming, anti-inflammatory effects. For a time, I also used Xolair (omalizumab) injections, a biologic sometimes prescribed off-label for MCAS. It initially provided noticeable symptom relief. However, I had to pause my beta blocker—a medication I rely on to manage hyperadrenergic POTS (hyperPOTS)—in order to receive the injections. That interruption destabilized my autonomic nervous system, causing a resurgence of symptoms like tachycardia, dizziness, and blood pressure swings. As a result, I ultimately had to discontinue Xolair, despite its potential benefits for MCAS.

The Results: What Changed for Me

It didn’t happen overnight. But within a few weeks of consistency, I started to feel the shift:

• 🔻 Itching and flushing decreased dramatically.
  I used to break out into hives or redness from the smallest triggers—heat, foods, stress, petting my dogs. Now, those episodes are rare, and much milder when they do happen.
• ⚡ Energy levels improved.
  I stopped feeling like my body was in crisis 24/7. I began to have stretches of real stamina—enough to have a full conversation without crashing.
• 🧠 Brain fog lifted.
  For the first time in years, I could think clearly. I was able to watch tv, converse with my partner, and even write this blog post with a mind that felt like mine again.
• 💚 My mood stabilized.
  The hopelessness I used to feel every morning started to fade. With better symptom control came real hope—and that changed everything.

Why This Worked for Me

I believe this protocol worked because it didn’t rely on a single treatment. It addressed multiple MCAS pathways—histamine, mast cell stability, inflammation, immune modulation—all at once.

And just as importantly:
✅ I listened to my body
✅ I worked with medical professionals
✅ I adjusted dosages and combinations slowly
✅ I tracked my responses carefully

This approach isn’t a miracle cure. But for me, it was a major turning point. I finally started feeling like I was managing MCAS—not just reacting to it.

Tips for Getting Started with Your Own MCAS Protocol

If you’re ready to try a multi-layered approach to managing MCAS, here are some lessons I learned that might help you build your own version of the Kitchen Sink Protocol:

🔄 1. Start Low and Go Slow

Many people with MCAS are extremely sensitive—even to things meant to help. Start with small doses, especially with supplements, and introduce one intervention at a time. Give your body space to respond.

👨‍⚕️ 2. Work With a Doctor Who Understands MCAS

If possible, find a practitioner who has experience treating mast cell disorders or chronic complex illnesses like ME/CFS or Long COVID. They can help guide you through medication options, interactions, and lab monitoring.

📓 3. Track Your Symptoms and Triggers

Keeping a daily log of what you eat, take, and experience can help you uncover hidden triggers and track whether a new intervention is helping or causing issues. I used a spreadsheet at first, then moved to an app.

🧪 4. Prioritize Tolerance Over Trendiness

It’s easy to get caught up in what’s “supposed” to help—especially in online forums—but always listen to your body first. Just because something works for others doesn’t mean it’s right for you.

🛍️ 5. Watch for Fillers and Additives

People with MCAS often react to dyes, preservatives, or binders in meds and supplements. Look for clean, hypoallergenic formulas and work with a compounding pharmacy if needed.

Final Thoughts: Hope, Not Hype

Living with MCAS can feel isolating, confusing, and exhausting. I know the fear that comes with eating a new food, trying a new supplement, or simply waking up unsure of what your body will do.

This protocol didn’t cure my MCAS—but it gave me my life back. It helped me break the cycle of constant flares and unpredictability. It taught me how to manage my condition, advocate for myself, and reclaim some peace of mind.

🙌 If you’re just beginning this journey:

Know that you’re not alone—and that a personalized, layered treatment approach might offer you more relief than you imagined possible.

If you have questions, want to share your story, or just need someone to compare notes with, feel free to leave a comment or email me directly. I’d love to hear from you.

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Sources:

Prescriptions

Name	Frequency	Why?
Cromolyn Sodium	a.c.	MCAS: mast cell stabilizer
Cyproheptadine	q.h.s.	MCAS: h1 blocker and ability to block serotonin receptors
Famotidine 20mg	b.i.d.	MCAS: h2 blocker
Hydroxyzine* 25mg, 50-75mg	a.c., q.h.s.	MCAS: h1 blocker
Ketotifen 3mg	t.i.d.	MCAS: mast cell stabilizer
Montelukast 10mg	q.h.s.	MCAS: allergic asthma
Naltrexone, low dose 4.5mg	q.d.	Reduce T cell dysfunction (T cell micro parts activate mast cells)
Zofran	prn.	MCAS: 5-HT3 blocker

OTCs

Name	Frequency	Why?
Benadryl 25mg	prn.	MCAS: anti-histamine
Claritin* / Xyzal*	q.h.s.	MCAS: 2nd gen h1 blocker
Zyrtec* 20mg / Allegra*	q.d.	MCAS: 2nd gen h1 blocker

*Every 60-90 days rotate Zyrtec or Allegra, Claritin or Hydroxyzine or Xyzal

Supplements

Name	Frequency	Why?
Liposomal Glutathione	q.d.	MCAS: reduces oxidative stress, stabilizes immune responses, and protects tissues from inflammation
Liposomal Vitamin C 500mg	q.d.	MCAS: breakdown histamine, stabilize mast cells
Luteolin 100mg	b.i.d.	MCAS: prevents mast cell degranulation
NAC 600mg	q.d.	MCAS: antioxidant, anti-inflammatory, and immune-modulating properties
Palmitoylethanolamide (PEA)	q.d.	MCAS: PEA helps downregulate mast cell degranulation and the release of inflammatory mediators like histamine and cytokines
Quercetin 250-500mg	b.i.d.	MCAS: stabilize mast cells
Umbrellux DAO	a.c.	MCAS: break down food derived histamine
Vitamin C 500mg/75mg bioflavonoids	q.d.	MCAS: breakdown histamine, stabilize mast cells
Vitamin D 5000 IU	q.d.	MCAS:

Intravenous

Name	Frequency	Why?
Benadryl IV	prn.	MCAS: anti-histamine

Injection

Name	Frequency	Why?
Aimovig 70mg	q.4week	Chronic Migraines: CGRP inhibitor, CGRP involved in mast cell degranulation
Epi-pen	prn.	MCAS: Anaphylaxis
Xolair 300mg/ml	q.4week/	MCAS: a monoclonal antibody that reduces the sensitivity of mast cells to allergens and other triggers

Nasal Inhalation

Name	Frequency	Why?
Xhance Nasal Spray 93mcg	b.i.d.	MCAS: help w nasal swelling

Cromolyn Sodium: Cromolyn sodium is a mast cell stabilizer that can help prevent the release of histamine and other inflammatory mediators from mast cells. It can help reduce symptoms such as flushing, itching, abdominal pain, nausea, and diarrhea. Cromolyn sodium is usually taken orally before meals and at bedtime. It may take several weeks to see the full effect of this medication. ^[1]“Cromolyn Sodium – FDA Prescribing Information,” Drugs.com, https://www.drugs.com/pro/cromolyn-sodium.html.

Cyproheptadine: Cyproheptadine can be a helpful medication for managing mast cell activation syndrome (MCAS), especially when symptoms include both histamine and serotonin-related effects. As an H1 antihistamine, it helps block the effects of histamine released by mast cells, reducing symptoms like itching, hives, and flushing ^[2]Simons, “Advances in H1-Antihistamines,” New England Journal of Medicine, https://doi.org/10.1056/NEJMra033121. It also blocks serotonin receptors, which may ease nausea, abdominal pain, and other gastrointestinal symptoms that often accompany MCAS ^[3]Kettelhut et al., “Cyproheptadine in the Treatment of Functional Gastrointestinal Disorders,” Pediatric Drugs, https://doi.org/10.1007/s40272-015-0132-6

Its sedating and appetite-stimulating properties can further support patients dealing with sleep disruption or appetite loss due to chronic inflammation ^[4]Afrin, Never Bet Against Occam, Sisters Media, 2016. Though not usually the first medication tried, cyproheptadine is a useful addition when standard antihistamines aren’t enough or when serotonin-driven symptoms are significant ^[5]Kaplan, Mast Cell Disorders, Humana Press, 2011.

Famotidine 20mg: Famotidine is an H2 antihistamine that can help block the action of histamine in the stomach and reduce gastric acid production. This can help with gastrointestinal symptoms such as heartburn, indigestion, and ulcers. Famotidine can also help with overall mast cell stability and reduce symptoms such as flushing, headache, and brain fog. Famotidine is usually taken once or twice daily, with or without food. ^[6]“Famotidine: 7 Things You Should Know,” Drugs.com, https://www.drugs.com/tips/famotidine-patient-tips.

Hydroxyzine 25mg, 50–75mg: Hydroxyzine is an H1 antihistamine that can help reduce the effects of histamine on the skin, eyes, nose, mouth, throat, and lungs. It can help with itching, hives, swelling, runny nose, sneezing, and wheezing. Hydroxyzine can also have a sedating effect and help with anxiety, insomnia, and nervousness. Hydroxyzine is usually taken three or four times a day, as needed.

^[7]“What Is the Medicine Hydroxyzine Pam 25 mg Used For?,” Healthfully, https://healthfully.com/medicine-25-mg-used-for-5113874.html. ^[8]“Hydroxyzine Uses, Dosage & Side Effects,” Drugs.com, https://www.drugs.com/hydroxyzine.html. ^[9]“Hydroxyzine: View Uses, Side Effects and Medicines,” 1mg, https://www.1mg.com/generics/hydroxyzine-210013.

Ketotifen 3mg: Ketotifen is a dual-action medication that acts as both an H1 antihistamine and a mast cell stabilizer. It can help prevent and treat symptoms such as itching, flushing, hives, swelling, abdominal pain, nausea, diarrhea, and anaphylaxis. Ketotifen can also help with brain fog and cognitive function by crossing the blood-brain barrier. Ketotifen is usually taken twice a day, in the morning and evening.

^[10]“Ketotifen for Mast Cell Activation Syndrome (MCAS),” Park Compounding Pharmacy, https://www.parkcompounding.com/ketotifen-mast-cell-activation-syndrome/. ^[11]“MCAS: Treatment,” Mast Attack, https://www.mastattack.org/2014/10/mcas-treatment/.

Montelukast 10mg: Montelukast is a leukotriene inhibitor that can help block the action of leukotrienes, which are inflammatory mediators released by mast cells and other cells. Leukotrienes can cause symptoms such as bronchoconstriction, mucus production, nasal congestion, and asthma attacks. Montelukast can help with respiratory symptoms and overall mast cell stability. Montelukast is usually taken once a day in the evening. ^[12]“Montelukast: View Uses, Side Effects and Medicines,” 1mg, https://www.1mg.com/generics/montelukast-210304.

Naltrexone, low dose 4.5mg: Naltrexone is an opioid antagonist that can help modulate the immune system and reduce inflammation by blocking the opioid receptors on mast cells and other cells. Naltrexone can help lower the release of histamine and other mediators from mast cells and improve symptoms such as pain, fatigue, mood swings, and brain fog. Naltrexone is usually taken at a low dose of 4.5mg once a day at night. ^[13]“What Is Low Dose Naltrexone (LDN)?,” Drugs.com, https://www.drugs.com/medical-answers/low-dose-naltrexone-ldn-3570335/.

Zofran: Zofran is an antiemetic medication that can help prevent and treat nausea and vomiting caused by various triggers, including mast cell activation. Zofran works by blocking the action of serotonin on the receptors in the brain and the gut that control nausea and vomiting. Zofran can also help with abdominal pain and diarrhea by reducing intestinal motility. Zofran can be taken orally or intravenously as needed or before exposure to a known trigger. ^[14]“Zofran: Package Insert / Prescribing Information,” Drugs.com, https://www.drugs.com/pro/zofran.html.

Benadryl 25mg: Benadryl is an H1 antihistamine that can help reduce the effects of histamine on the skin, eyes, nose, mouth, throat, and lungs^[15]“Diphenhydramine (Benadryl): Antihistamine for Allergy Relief,” Drugs.com, https://www.drugs.com/benadryl.html. It can help with symptoms such as itching, hives, swelling, runny nose, sneezing, and wheezing^[16]“Diphenhydramine: Uses, Side Effects, and Warnings,” Mayo Clinic, https://www.mayoclinic.org/drugs-supplements/diphenhydramine-oral-route/description/drg-20070561. Benadryl can also have a sedating effect and help with anxiety and insomnia^[17]“Benadryl for Sleep: Can You Use It?,” Medical News Today, https://www.medicalnewstoday.com/articles/benadryl-for-sleep. Benadryl is usually taken every four to six hours as needed or before exposure to a known trigger^[18]“Diphenhydramine (Oral Route),” Mayo Clinic, https://www.mayoclinic.org/drugs-supplements/diphenhydramine-oral-route/proper-use/drg-20070561.

Claritin / Xyzal: Claritin and Xyzal are second-generation H1 antihistamines that can help reduce the effects of histamine on the skin, eyes, nose, mouth, throat, and lungs^[19]“Loratadine (Claritin),” Drugs.com, https://www.drugs.com/loratadine.html; “Levocetirizine (Xyzal),” Drugs.com, https://www.drugs.com/mtm/xyzal.html. They can help with symptoms such as itching, hives, swelling, runny nose, sneezing, and wheezing^[20]“Second-Generation Antihistamines,” American Academy of Allergy, Asthma & Immunology, https://www.aaaai.org/tools-for-the-public/allergy-/drug-guide/antihistamines.

Claritin and Xyzal have less sedating effects than first-generation antihistamines and may also help with brain fog and cognitive function^[21]Simons, F.E.R. “Advances in H1-antihistamines,” New England Journal of Medicine, 2004. https://www.nejm.org/doi/full/10.1056/NEJMra033121. Claritin and Xyzal are usually taken once a day, with or without food^[22]“How to Take Xyzal and Claritin,” Healthline, https://www.healthline.com/health/allergies/xyzal-vs-claritin.

Zyrtec 20mg / Allegra: Zyrtec (cetirizine) and Allegra (fexofenadine) are second-generation H1 antihistamines that can help reduce the effects of histamine on the skin, eyes, nose, mouth, throat, and lungs. They can help with symptoms such as itching, hives, swelling, runny nose, sneezing, and wheezing ^[23]Cleveland Clinic. “Antihistamines.” Cleveland Clinic, last modified October 13, 2023. https://my.clevelandclinic.org/health/treatments/antihistamines. Zyrtec and Allegra may have more antihistamine potency than Claritin and Xyzal but may also cause more drowsiness and dry mouth ^[24]Drugs.com. “What’s the Difference Between Allegra and Zyrtec?” Drugs.com, last updated March 3, 2022. https://www.drugs.com/medical-answers/allegra-zyrtec-difference-3130012. Zyrtec is generally considered more sedating, while Allegra is less likely to cross the blood-brain barrier and is thus less likely to cause drowsiness ^[25]Drugs.com. “Allegra (Fexofenadine) – Side Effects, Dosage, and More.” Drugs.com, accessed May 28, 2025. https://www.drugs.com/allegra.html. Both medications are usually taken once a day, with or without food, but according to my specialist, the dosage can be increased to twice daily if needed ^[26]GoodRx. “Zyrtec Dosage: How Much Should I Take?” GoodRx, last modified March 14, 2023. https://www.goodrx.com/zyrtec/dosage.

Liposomal Glutathione: Glutathione, often referred to as the body’s “master antioxidant,” plays a critical role in supporting individuals with mast cell activation syndrome (MCAS) by reducing oxidative stress, stabilizing immune responses, and protecting tissues from inflammation. In MCAS, mast cells become overly reactive and release mediators like histamine, prostaglandins, and cytokines inappropriately. This process is often worsened by oxidative stress, which can trigger mast cell degranulation. Glutathione neutralizes reactive oxygen species (ROS), helping to prevent this chain reaction and reduce mast cell activation ^[27]Pizzino et al., “Oxidative Stress: Harms and Benefits for Human Health,” Oxidative Medicine and Cellular Longevity, https://doi.org/10.1155/2017/8416763.

Furthermore, glutathione helps regulate immune function and inflammation by modulating redox-sensitive signaling pathways such as NF-κB, which is commonly activated in chronic inflammatory states like MCAS. By maintaining redox balance, glutathione can reduce inappropriate immune signaling and downstream mediator release ^[28]Forman et al., “Glutathione: Overview of Its Protective Roles, Measurement, and Biosynthesis,” Molecular Aspects of Medicine, https://doi.org/10.1016/j.mam.2008.08.006. Many individuals with MCAS also struggle with detoxification issues due to genetic variations or chronic inflammation. Glutathione supports phase II liver detoxification and helps eliminate toxins that might otherwise provoke mast cell reactions ^[29]Ballatori et al., “Glutathione Dysregulation and the Etiology and Progression of Human Diseases,” Biological Chemistry, https://doi.org/10.1515/BC.2009.033.

For some patients, direct glutathione supplementation or the use of precursors like N-acetylcysteine (NAC) can help restore deficient levels and improve symptoms. Overall, maintaining adequate glutathione levels is a foundational strategy in MCAS protocols aimed at lowering reactivity and promoting immune resilience.

Liposomal Vitamin C 500mg: Liposomal vitamin C is a form of vitamin C that is encapsulated in liposomes, which are tiny spheres of fat that protect the vitamin C from degradation and enhance its absorption in the gut ^[30]Amy Myers MD. “Liposomal Vitamin C – Bioavailable Liquid.” Amy Myers MD. Accessed May 28, 2025. https://store.amymyersmd.com/products/liposomal-vitamin-c. Vitamin C is an antioxidant that can help prevent oxidative damage to cells and tissues caused by free radicals and inflammation ^[31]Hemilä, Harri. “Vitamin C and Infections.” Nutrients 9, no. 4 (2017): 339. https://doi.org/10.3390/nu9040339. Vitamin C can also help lower histamine levels by supporting the production of the histamine-degrading enzyme DAO ^[32]Maintz, Laura, and Natalija Novak. “Histamine and Histamine Intolerance.” The American Journal of Clinical Nutrition 85, no. 5 (2007): 1185–1196. https://doi.org/10.1093/ajcn/85.5.1185. Liposomal vitamin C is usually taken once or twice a day, preferably on an empty stomach ^[33]Amy Myers MD. “Liposomal Vitamin C – Bioavailable Liquid.” Amy Myers MD. Accessed May 28, 2025. https://store.amymyersmd.com/products/liposomal-vitamin-c.

Luteolin 100mg: Luteolin is a flavonoid that can help modulate the immune system and reduce inflammation by inhibiting the activation and release of mast cells and other inflammatory cells ^[34]Theoharides, Theoharis C., Julia Alysandratos, Dimitrios Angelidou, Bodi Zhang, Magda Asadi, Magdalini Francis, and R. E. Kalogeromitros. 2015. “Luteolin as a Therapeutic Option for Mast … Continue reading. Luteolin can also help lower histamine levels by blocking the action of histamine on the H1 receptors ^[35]Healing Histamine. “Luteolin for Mast Cells, Histamine and Brain Fog?” Healing Histamine. Accessed May 28, 2025. … Continue reading. Luteolin can help with symptoms such as flushing, itching, hives, swelling, abdominal pain, nausea, diarrhea, and brain fog ^[36]Theoharides, Theoharis C., Julia Alysandratos, Dimitrios Angelidou, Bodi Zhang, Magda Asadi, Magdalini Francis, and R. E. Kalogeromitros. 2015. “Luteolin as a Therapeutic Option for Mast … Continue reading. Luteolin is usually taken once or twice a day, with or without food ^[37]Healing Histamine. “Luteolin for Mast Cells, Histamine and Brain Fog?” Healing Histamine. Accessed May 28, 2025. … Continue reading.

N-Acetylcysteine (NAC): N-Acetylcysteine (NAC) may be a valuable adjunct in managing mast cell activation syndrome (MCAS) due to its antioxidant, anti-inflammatory, and immune-modulating properties. One of its key functions is serving as a precursor to glutathione, the body’s master antioxidant, which helps neutralize oxidative stress—a known trigger for mast cell degranulation. By increasing intracellular glutathione, NAC helps stabilize mast cells and potentially reduces the release of histamine and other inflammatory mediators ^[38]Atkuri et al., “N-Acetylcysteine—A Safe Antioxidant for Clinical Use,” Current Opinion in Pharmacology, https://doi.org/10.1016/j.coph.2007.08.005.

NAC also plays a role in modulating inflammation by inhibiting nuclear factor kappa B (NF-κB), a critical transcription factor involved in pro-inflammatory signaling pathways. This is particularly important for MCAS patients, whose immune systems often overreact to benign stimuli ^[39]Rushworth and Megson, “Existing and Potential Therapeutic Uses for N-Acetylcysteine,” Pharmacology & Therapeutics, https://doi.org/10.1016/j.pharmthera.2013.03.006. In addition, NAC supports liver detoxification and can aid patients with chemical sensitivities or impaired biotransformation pathways. Its mucolytic properties may also benefit those with MCAS-related respiratory symptoms. Overall, NAC’s broad-spectrum actions make it a supportive option for many living with MCAS ^[40]Samuni et al., “The Chemistry and Biological Activities of N-Acetylcysteine,” Biochimica et Biophysica Acta, https://doi.org/10.1016/j.bbagen.2012.10.005.

Palmitoylethanolamide (PEA): Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide that shown promise in the management of mast cell activation syndrome (MCAS) due to its anti-inflammatory, analgesic, and mast cell-modulating properties. PEA works by interacting with several cellular receptors and mechanisms, notably the peroxisome proliferator-activated receptor alpha (PPAR-α), which plays a key role in reducing inflammation and immune dysregulation. Through this pathway, PEA helps downregulate mast cell degranulation and the release of inflammatory mediators like histamine and cytokines, which are central to MCAS symptoms ^[41]Petrosino and Di Marzo, “The Pharmacology of Palmitoylethanolamide and First Data on the Therapeutic Efficacy of Some of Its New Formulations,” British Journal of … Continue reading.

Additionally, PEA has demonstrated a strong safety profile and is well tolerated even in sensitive populations, which makes it a suitable adjunct to more conventional MCAS therapies like antihistamines or mast cell stabilizers. Some clinical and preclinical studies have observed benefits in reducing neuroinflammation, pain, and allergic responses, which may be particularly relevant for MCAS patients dealing with systemic symptoms ^[42]Facci et al., “Mast Cells Express a Peripheral Cannabinoid Receptor with Differential Sensitivity to Anandamide and Palmitoylethanolamide,” Proceedings of the National Academy of … Continue reading.

In summary, PEA may offer a multifaceted approach to managing MCAS by supporting immune balance, reducing mast cell reactivity, and alleviating chronic inflammation and pain.

Quercetin 250–500mg: Quercetin is a flavonoid that can help modulate the immune system and reduce inflammation by inhibiting the activation and release of mast cells and other inflammatory cells.

^[43]Andrea Czompa et al., “Quercetin: A Powerful Antioxidant and Anti-inflammatory Agent,” Current Opinion in Food Science 24 (2018): 58–66, https://doi.org/10.1016/j.cofs.2018.11.00.

Quercetin can also help lower histamine levels by supporting the production of the histamine-degrading enzyme DAO and blocking the action of histamine on the H1 receptors. Quercetin can help with symptoms such as flushing, itching, hives, swelling, abdominal pain, nausea, diarrhea, and brain fog. Quercetin is usually taken once or twice a day, preferably on an empty stomach.

^[44]Jiří Mlček et al., “Quercetin and Its Anti-Allergic Immune Response,” Molecules 21, no. 5 (2016): 623, https://doi.org/10.3390/molecules21050623.

^[45]“Quercetin for MCAS,” Through the Fibro Fog, accessed May 28, 2025, https://www.throughthefibrofog.com/quercetin-supplement/.

^[46]“Umbrellux DAO – What You Need to Know,” Healthy Habits Living, accessed May 28, 2025, https://www.healthyhabitsliving.com/blogs/be-healthy/umbrellux-dao-what-you-need-to-know.

Umbrellux DAO: Umbrellux DAO is a supplement that contains DAO, the enzyme that breaks down histamine in the gut. Umbrellux DAO can help lower histamine levels by enhancing the metabolism of dietary histamine and preventing its absorption into the bloodstream. Umbrellux DAO can help with symptoms such as flushing, itching, hives, swelling, abdominal pain, nausea, diarrhea, and headache. Umbrellux DAO is usually taken 15 to 20 minutes before a meal that contains histamine-rich foods.

Vitamin C 500mg/75mg bioflavonoids: Vitamin C with bioflavonoids is a combination of vitamin C and plant compounds that have antioxidant and anti-inflammatory properties. Vitamin C can help lower histamine levels by supporting the production of the histamine-degrading enzyme DAO. ^[47]C. A. B. Clemetson, “Histamine and Ascorbic Acid in Human Blood,” Free Radical Biology and Medicine 8, no. 1 (1980): 19–25, https://doi.org/10.1016/0891-5849(80)90153. Bioflavonoids can help stabilize mast cells and prevent the release of histamine and other mediators. Vitamin C with bioflavonoids can help with symptoms such as flushing, itching, hives, swelling, abdominal pain, nausea, diarrhea, and brain fog. Vitamin C with bioflavonoids is usually taken once or twice a day, with or without food.

Vitamin D 5000 IU: According to some sources, vitamin D may help MCAS by stabilizing mast cells, regulating the immune system, and functioning as an anti-inflammatory.

^[48]“Will Vitamin D Help or Hurt You if You Have Mast Cell Activation Syndrome or Histamine Intolerance?,” Mast Cell 360, accessed May 28, 2025, … Continue reading

^[49]Tania Dempsey, “The Metabolic Syndrome Puzzle: The Vitamin D and MCAS Connection,” Dr. Tania Dempsey, accessed May 28, 2025, … Continue reading

Vitamin D interacts with mast cells to make them less reactive and less likely to activate inappropriately.

^[50]Tania Dempsey, “The Metabolic Syndrome Puzzle: The Vitamin D and MCAS Connection,” Dr. Tania Dempsey, accessed May 28, 2025, … Continue reading

In the absence of the necessary vitamin D, mast cells may lack this calming influence and become more prone to confusion and overreaction.

^[51]Tania Dempsey, “The Metabolic Syndrome Puzzle: The Vitamin D and MCAS Connection,” Dr. Tania Dempsey, accessed May 28, 2025, … Continue reading

However, vitamin D levels should be checked and supplemented appropriately, as too much or too little vitamin D may have adverse effects on health.

^[52]“Will Vitamin D Help or Hurt You if You Have Mast Cell Activation Syndrome or Histamine Intolerance?,” Mast Cell 360, accessed May 28, 2025, … Continue reading

Aimovig 70mg: Aimovig is a monoclonal antibody that blocks the action of calcitonin gene-related peptide (CGRP), a molecule that is involved in migraine pathophysiology. Aimovig can help prevent migraine attacks by reducing the activation of trigeminal nerve fibers and mast cells that trigger pain and inflammation in the brain. Aimovig can also help reduce migraine frequency, severity, and duration. Aimovig is usually injected subcutaneously once a month. ^[53]Aimovig: 7 things you should know – Drugs.com. https://www.drugs.com/tips/aimovig-patient-tips.

Epi-pen: Epi-pen is an auto-injector that delivers epinephrine (adrenaline), a hormone that counteracts the effects of severe allergic reactions (anaphylaxis). Epi-pen can help reverse symptoms such as low blood pressure, rapid heart rate, difficulty breathing, swelling in the throat, and loss of consciousness. Epi-pen is used as an emergency treatment for anaphylaxis and should be followed by immediate medical attention. Epi-pen is injected into the outer thigh muscle as soon as possible after exposure to a known or suspected trigger.

^[54]“How to Use Your EpiPen,” American Academy of Allergy, Asthma & Immunology, accessed May 28, 2025, … Continue reading

Xolair 150mg/ml: Xolair (omalizumab) is a monoclonal antibody that specifically binds to immunoglobulin E (IgE), a key antibody involved in triggering allergic reactions. By binding to IgE, Xolair prevents it from attaching to mast cells and basophils, which are immune cells responsible for releasing histamine and other inflammatory mediators during allergic responses. This action helps reduce the frequency and severity of allergic symptoms, including those seen in mast cell activation syndrome (MCAS) and chronic spontaneous urticaria. Xolair is administered by subcutaneous injection, usually once every 2 to 4 weeks, under the supervision of a healthcare provider. It is typically reserved for patients with moderate to severe allergic conditions who do not respond adequately to standard treatments. Common side effects may include injection site reactions, headaches, and an increased risk of infections. Because Xolair affects the immune system, it requires careful monitoring by a specialist. ^[55]“Xolair (Omalizumab) Injection,” U.S. National Library of Medicine, last updated March 9, 2023, https://medlineplus.gov/druginfo/meds/a604035.html.

IV Benadryl: IV Benadryl is a brand name for diphenhydramine, a first-generation H1 antihistamine that helps reduce the effects of histamine on the skin, eyes, nose, mouth, throat, and lungs. It is effective in relieving symptoms such as itching, hives, swelling, runny nose, sneezing, and wheezing. Additionally, IV Benadryl has sedative properties that can aid with anxiety and insomnia. It is typically administered every four to six hours as needed or prior to exposure to a known allergen or trigger. ^[56]“Diphenhydramine Injection,” U.S. National Library of Medicine, last updated August 24, 2023, https://medlineplus.gov/druginfo/meds/a682539.html.

IV Benadryl is also utilized in severe cases of mast cell activation syndrome (MCAS) due to its ability to block histamine release and other inflammatory mediators from mast cells. By rapidly suppressing mast cell activation, it can reverse critical symptoms such as hypotension (low blood pressure), respiratory distress, and anaphylaxis. Furthermore, IV Benadryl helps stabilize mast cells, reducing the risk of rebound symptoms as the medication wears off. In life-threatening MCAS, it may be administered as a continuous infusion under close medical supervision to maintain symptom control. ^[57]Castells M., “Mast Cell Activation Syndrome and Treatment,” Immunology and Allergy Clinics of North America 38, no. 3 (2018): 417–431, https://doi.org/10.1016/j.iac.2018.03.003.