Mast Cell Activation Syndrome (MCAS)

Woman suffering from symptoms.

“I’ve been treated for SIBO multiple times, but still have symptoms.”

“I’m sensitive to everything – smells, supplements, foods, you name it!”

“I get rashes/hives without any known trigger  – dermatologists can’t figure out how to help me.”

“I’m sensitive to a lot of foods, and can only eat a few foods.”

“I’ve done a lot of gut testing and treatments, but nothing seems to make my symptoms completely go away.”

I hear at least one of these concerns from patients in whom I suspect Mast Cell Activation Syndrome (MCAS), which I prefer to call Mast Cell Hyperactivity.  

Mast cells, which are located all over the body in tissues (but not in the bloodstream), are part of the immune system.  They are intended to protect us! Mast cells release over 200 chemicals like histamine and heparin when responding to a potential threat in the body. In the right quantity, these chemicals are anti-inflammatory and increase blood flow (to eliminate infections, allergens, or inflammation). Histamine is actually involved in motivation and wakefulness. 

When they become chronically over-active, the molecules they release can lead to a variety of symptoms. MCAS can affect almost any organ or tissue. Some people have more gut symptoms, others experience more respiratory symptoms; some have more skin issues, others have more cognitive issues. And anyone with MCAS can have symptoms that affect multiple areas of the body.

This pathophysiological reaction is not widely recognized by mainstream medicine, since it is a relatively new phenomenon, so it is a frustrating condition to identify and treat.  And since it is a systemic imbalance, patients can have almost any symptom (however, gastrointestinal and neurological symptoms are most common).

Testing for MCAS is not very accurate, due to the short-lived nature of the molecules that we can test for, so we have to rely on a collection of symptoms and the response to treatments to make a diagnosis. There are a lot of symptoms associated with MCAS. A lot! Anyone can develop “medical student syndrome” just by reading through these lists (especially the list found on this site)! And many of the symptoms in MCAS can be attributed to other conditions!

There are a grouping of symptoms that currently seem to have a higher co-occurrence of MCAS (see resources for articles), including the following:

  1. Hypermobility/EDS (Ehlers Danlos Syndrome) body types
  2. Dysautonomia (e.g. POTS or postural orthostatic tachycardia syndrome) or small fiber neuropathy
  3. Autoimmunity
  4. Gastroparesis (some clinicians use low elastase on stool testing, <200, as a marker as well of mast cell involvement in the GI system)
  5. Sensitive to smells, sounds, EMFs, light, most pharmaceuticals.
  6. Adverse childhood experiences (ACEs), medical trauma, gaslighting. 

Some group these into the “Pentad Super Syndrome” (POTS/dysautonomia, MCAS, GI dysfunction, autoimmunity, and hyper mobility type EDS) or the “Terrible Trifecta” (MCAS, POTS/dysautonomia, hyper mobile EDS).

Instead of reading through the list of symptoms, however, I recommend starting with the questionnaire below. It is based off the questionnaire found in Dr. Lawrence Afrin’s 2014 article, “A concise, practical guide to diagnostic assessment for mast cell activation disease.” I just simplified the language in the list, and categorized the questions differently (to make it easier to fill out)!


The role of mast cells in chronic disease states is still poorly understood, and some research is finding associations of various conditions with mast cell hyperactivity.  These include:

  • Fibromyalgia (related to mast cells in the thalamus) (see this article)
  • Small fiber neuropathy (81% may have MCAS per this article)
  • Migraines
  • Dysautonomia (e.g. POTS)
  • Chronic pain (including CRPS, chronic regional pain syndrome) (see this article)
  • OCD (Obsessive Compulsive Disorder)
  • Unexplained Urticaria (hives)
  • Anxiety (one of the most common symptoms we see in MCAS patients)
  • Difficulties concentrating (including ADHD, bipolar conditions)


Right now, there is no known cause.  In functional medicine, we currently suspect that the following are the primary triggers.

From experience, excessive indoor mold exposure (current or past) and viral reactivations are the most common triggers I see.

I’ve had a handful of patients put their symptoms into remission by addressing the following (which is not a quick fix), but I do believe that this syndrome can be reversed – it just takes work!

  • Persistent stress (the hormone cortisol causes mast cells to release their inflammatory molecules)
  • Unresolved trauma
  • Not feeling safe in our bodies, or in control of our life
  • Excessive stimulation without allowing prolonged relaxation (e.g. always on-the-go, lots of stress, excessive exercise)
  • Structural issues
    • Ehlers Danlos Syndrome
    • Cervical issues (I highly recommend evaluation for CCI aka Craniocervical Instability and C1/C2 imbalances per a chiropractor that practices the Blaire Technique or NUCCA)
    • Head trauma including from mild repetitive sports trauma (gymnastics, martial arts) 
  • Tick-borne illness
  • Gastrointestinal dysbiosis
    • Parasites (but also can occur in the liver, gall bladder, lungs, bladder, rarely the brain – location best identified via Autonomic Response Testing) – best addressed with herbals, often cyclical treatments for 6 months (e.g. with Wormwood, Myrrh, mimosa pudica, prescription anti-parasites)
    • Biofilm build up
    • SIBO (Small Intestinal Bacterial Overgrowth – aka small bowel dysbiosis) and/or SIFO (Small Intestinal Fungal Overgrowth)
  • Virus reactivation
  • “Unusual” triggers (e.g. immune reactivity to Chlamydia pneumonia, Mycoplasma pneumonia)
  • “External parasites” (e.g. toxic relationships, jobs)
  • Genetic predispositions
  • Impaired bile flow
  • Liver stress (e.g. from pharmaceuticals, alcohol use)
  • Gastrointestinal imbalances 
  • Indoor mold toxins (aka mycotoxins)
  • Multiple chemical sensitivity 
  • Chemical exposure in home/work
  • Pesticides (especially glyphosate)


There are some imperfect ways to test for MCAS, which involve blood tests, urine tests, or tissue biopsies. Since this is often an “expensive” condition, I highly recommend using treatments as “tests” rather than trying to get a diagnosis from any of the following tests (since each can be hundreds if not over a thousand dollars when/if insurance doesn’t cover it). But for completeness, the current tests include:

  • PGD2
  • Total IgE
  • Total IgG4
  • Immune IgE allergy panel (RAST for alpha-gal, casein, gluten, dust mites, fungi, grass, pollen)
  • Anti-IgE receptor antibody (basophil activation)
  • Food intolerance panel (IgG4) – ideally only eat chicken and rice for 2-3 days prior to this, per Dr. Theoharides
  • Heparin
  • IL-4, IL-6, IL-31, IL-33
  • Tryptase
  • CCL2, CXCL8 (IL-8)
  • Urine 24 hour tests (but must be kept cold for accuracy):
    • Methylhistamine or MIA
    • PGD2
    • 23BPG+2,3-Dinor-11-beta-PGF2-alpha
  • GI biopsies (latest biomarkers include CD117 stained mast cells, tryptase depletion index)

However, these are abnormal in only a small percentage of people who I suspect to have MCAS (and who subsequently respond to treatments), so I rarely run these tests anymore.  Dr. Theoharides points out, too, that there are more important molecules involved that we currently don’t measure routinely, including IL-31 and Platelet Activating Factor (PAF).  And for those with suspected chronic spontaneous urticaria, and basophil activation test (BAT) may be warranted. 

Other tests to consider:

  • NeuroQuant (an imaging test), which can be particularly good at showing hyperactivity of certain ares of the brain (e.g. limbic system and the need to calm it down!)
  • Homocysteine (if high, associated with high histamine, under-methylation, or even lead toxicity)

Most diagnoses at this time, however, are based off medical history and the collection of symptoms that suggest MCAS.  And I would add the response to treatments can be a “test” as well (although a treatment must be given 6-8 weeks to work before considering it ineffective).  I’ve listed a lot of treatment potentials below.

The questionnaire at the end of this article is one of the more validated ways to diagnose suspected MCAS. It is based off symptoms, medical history, and test results. It will take 5-10 minutes to complete, and there is no need to share email information – completing it will just give you a score.

We must remember that MCAS is still a poorly understood condition, and information is constantly evolving. Right now, we don’t have good tests to definitively diagnose MCAS.

Why is it so difficult to receive a diagnosis from tests?

  • First, most of the testing occurs when someone either doesn’t have symptoms, or in the middle of an episode of symptoms.
  • Second, the chemicals released by mast cells are only circulating in the body (i.e. testable) for a short time – often only a few minutes – and require particular temperatures to stay stable during transportation to the testing facility.
  • Third, most tests available are only able to be run through a few laboratories (so many samples are shipped to these locations).

However, the symptoms of MCAS are often attributable to other illnesses, so I don’t recommend considering MCAS as a diagnosis based solely off a list of symptoms. I’ve unfortunately seen patients (and my colleagues in functional medicine) falsely self-diagnose just off a list of symptoms.

The following questionnaire can help, but response to treatments are something to add to the “diagnosis”. Luckily, most treatments can be purchased over the counter (but the timing and dosing of these matters, which is why I recommend appropriate guidance from a medical or nutrition professional).


The main focus needs to be finding the right combination of treatments to calm down symptoms before taking a deep dive into triggers so the body can handle treatments better.  This can involve trial/error, so be patient!  As you see below, functional and integrative medicine has MANY options for treatment, so please work with a knowledgeable practitioner on use of these.  In my experience, many with mast cell hyperactivity are very sensitive to treatments and may need to start with 1/4 of a dose, single ingredients, or even use a pinch of a treatment in 8oz of water and build up slowly.  One new treatment option every 2-3 weeks is also recommended, since it can take 6 weeks or more to see improvement (and more treatments are not better in MCAS).

The list of treatments below is long, which I categorize according to their most powerful functions. I generally try to have 3-5 treatments for the symptoms of my mast cell hypersensitivity patients, adding one at a time.  My comprehensive approach, though, depends on the most dominant symptoms (e.g. hives versus gut versus neurological), and include the following:

  1. Always address the basics first (building blocks to a healthy body): replete nutrient and mineral deficiencies, drink clean filtered water with added electrolytes (Clearly Filtered, Berkey, or Reverse Osmosis filters best), have a bowel movement daily, and start addressing the environment where someone lives.
  2. “Non-pill” neurological support (e.g. limbic system inhibition, vagal nerve support, neuroinhibition)
  3. Work on avoiding triggers of mast cells, especially uncontrolled stress.
  4. Anti-histamines
  5. Mast cell stabilizers 
  6. Inhibitory treatments per symptoms
  7. Additional support if indicated from labs, symptoms

See the list of possible treatments below.  Note that these are provided for educational purposes, and are not intended to be used for personal treatment without the guidance of a practitioner.  Many with MCAS are sensitive to treatments, which often can be due to added binders in the medications (so compounded prescriptions may be better). 

Rebalance the nervous system: Especially the limbic system (which “turns on” mast cells). There are many programs for this, and they are probably the most effective tool for support (more than any pill/diet)!  I’ve had some report significant improvements within just one week of starting a program!  Programs I recommend include:

Address the Environment: What we breathe in and put on our bodies affects our health!

  • Start with the Environmental Working Group, and aim to get all cleaning products, topical products (shampoos, lotions, makeup, etc) under a “4” according to the EWG.
  • Next step is to address what your food is stored in.  Limit plastic use to frozen items, and change all other storage containers to glass, and make sure plates/glasses don’t have lead, and cooking pots/pans are stainless steel, ceramic, or cast iron.
  • Address the air you breathe in daily (see below).
  • Limit electronic stimulation (including wifi) in the bedroom. Look into a Trifield Meter to measure exposure.

Gut Health: Daily bowel movements, ideally not loose or diarrhea-like, are essential.  Constipation will make mast cell hyperactivity worse!  Also, many mast cells are near nerves that are part of the autonomic nervous system, and vagus nerve imbalances (the nerve that connects gut to the brain) will complicate  symptoms even more.

Clean Air, for both indoor and outdoor air.  Our pituitary (a “master gland” in the body) is near our nasal passages, and play a huge role in immunity (and thus mast cell activity).  Consider a good quality air filter such as Air Doctor or Austin Air in the bedroom and office (or the 2 most common locations where you spend your time), clean air ducts at least once a year, clean drapes/curtains a few times a year, and keep HVAC cleaned with yearly maintenance.  

Support:  At least weekly if not daily include someone in your life who is supportive, such as a mindfulness-based therapist or counselor, practitioners and/or health coaches that believe you and advocate for you, and family/friends that listen to you without judgement.

Nutrition: Trial of a low-histamine diet (for recipe ideas, I recommend the book “The 4-Phase Histamine Reset Plan” by Dr. Becky Campbell). If no improvements, even small improvements, within 3-4 weeks on this plan, do not continue (histamine from the diet doesn’t always trigger mast cell symptoms – can be other molecules released by mast cells that are the cause of symptoms!).

  • Focus less on foods to avoid, and more on adding foods for support.  For example, some examples of foods that can REDUCE histamine include: Collard greens, zucchini, arugula, onion, fresh/dried herbs, apples, blueberries, pomegranate, egg yolk, apple cider vinegar, white rice.  Additional list of foods found here.
  • Many with MCAS get immune “PTSD” to foods, so consider using supportive therapies like a PTSD neurofeedback machine (I learned about the benefits of this from Jaban Moore DC who uses a Clear Mind machine to help someone get out of a PTSD state). 
  • Some really sensitive patients, if weight loss isn’t a concern, may do better with periodic liquid fasting and even a “carnivore” diet (these definitely need to be supervised by a practitioner)

Water: Many chemicals can trigger mast cells, and tap water (or low quality filtered water) has many chemicals that can be triggers.  I recommend drinking good quality filtered water – some of my favorite filters include Berkey and Clearly Filtered.  Many filters remove beneficial elements, so I also recommend adding mineral drops (these also reduce acidity of the water). My go-to brand is BodyBio, found on Fullscript.

Stress/Relaxation: Stress is a significant trigger of mast cells, so a daily relaxation habit is key to helping calm mast cells. 

  • A big part of this is supporting and stimulating the vagus nerve (and/or make sure the structure of the vagus nerve is not impaired, e.g. in the neck or near diaphragm); some examples include EFT (Emotional Freedom Technique), acupuncture, gentle craniosacral work, or working with a functional neurologist

Sleep: Mast cells have a “circadian rhythm”, and good sleep routine/quality is essential to restore normal activity.

We have multiple receptors (i.e. “locks”) that histamine binds to, but only 2 classes of medicine to bind to H1 and H2 receptors.

  • H1 blockers up to 3x/day: Examples include Tagamet, Pepcid, Zantac before meals (I mainly recommend these if gut symptoms are present)
  • H1 Blockers up to 3x/day: Examples include Allegra (least likely to cause sedation), Zyrtec, Claritin (weakest but may be best to start with if sensitive, some reports have found intra-vaginal use to be helpful for vaginal pain), Xyzal (particularly good if skin issues are present)
  • Diphenhydramine (Benadryl): I prefer Genexa brand (cleaner brand, can use for burning mouth and may help in compounded suppository form for vaginal pain and interstitial cystitis)


  • Hydroxyzine (great for insomnia as well)
  • Some psychiatric medications show anti-histamine and mast cell stabilizing effects, per Dr. Mary Beth Ackerley:
    • Fluvoxamine, lower dose often preferred (anti-mast cell, appears to be antiviral and improve blood flow, anti-inflammatory by stopping cytokine production); may be useful in OCD, tinnitus, PANS
    • Mirtazapine, low dose with low dependency risks (helps with weight gain, food reactions, sleep)
    • Nortriptyline (H1, H2, H3 blocker; good for pain especially with LDN, migraines, sleep)
    • Seroquel and trazodone also have some anti-histamine actions

Herbal/Supplement treatments:

  • Resveratrol
  • Red sage
  • Bromelain
  • CBD (even as suppository)
  • Stinging nettles (anti-inflammatory; one of my go-to recommendations, starting with tea)
  • Moringa (strong anti-histamine actions)
  • Spirulina (some anti-histamine actions)
  • Zatidor eye drops (can use in saline for nasal rinse as well)
  • Nasochrom in nose
  • Singulair (but may cause depression/anxiety)
Single Ingredient Supplements:
  • Bacopa moniera before meals (Bacopa works similar to cromolyn)
  • Nettle tea (2 oz before meals; brewed for 15 min can make an infusion aka stronger tea)
  • Quercetin: 250mg to 3000mg daily
  • AllQlear – Tryptase inhibitor before meals (less commonly effective, but taste good!)
  • Luteolin (bioflavenoid that is an H3 blocker as well); good for “brain and gut” symptoms
  • Rutin (bioflavenoid)
  • PEA (palmitoylethanolamide) – up to 3 grams daily

Pharmaceuticals such as:

  • Gastrocrom before meals
  • Compounded cromolyn sodium (nasal form can help brain fog, some individuals have used for tinnitus in ear; some practitioners use compounding pharmacies to be used as a nebulizer)
    • Compounded Ketotifen (orally or nasal use) 0.25-6mg
  • Singulair
  • LDN (low dose naltrexone) 0.25-4.5mg: Particularly good for those with pain, brain fog, if combined with alpha lipoic acid can help neuropathy
  • Less commonly used:
    • Imantinab
    • Omalizumab (for hives in particular)
Combination Products
  • NeuroProtek or PureLut before meals (developed by Dr. Theoharides; have luteolin)
  • Mirica 
  • Resveratrol Supreme (this has quercetin as well) 
  • SunBalance (has PEA, luteolin, and quercetin) before meals
  • HistaminX
  • HistaEze
  • NeuroFlam NT (has luteoline, Chinese skullcap)

The chemicals that mast cells release are “excitatory”, and the following act opposite of this (aka “calming” or “inhibitory”):

  • Taurine
  • Micronized progesterone
  • GABA
  • Glycine
  • Melatonin

The brain and nervous system is always involved in MCAS, and the following can support healthy neuron and cell membranes:

  • Bioactive lipids:
    • Phosphatidylcholine (PC), up to 5 grams daily (tastes terrible!): Most effective when combined with butyrate.  Also good for bile.  Can combine taurine, glycine and choline for less expensive option. 
    • CBD (ideally organic), particularly effective for anxiety, sleep, and pain
    • PEA: Particularly beneficial when combined with luteolin, CBD per Mary Beth Ackerley MD
    • Butyrate (best used with PC)
  • Stress (mental and physical)
  • Strenuos exercise
  • Excess estrogen or high estrogen fluctuations associated with period (e.g. birth control, hormone replacement therapy)
  • Wifi or EMF sensitivity (we are all exposed to this daily, unfortunately, but there are ways to decrease exposure); see this podcast for more information, and consider purchasing a Tri-Field Meter to identify where you may be getting high exposure to electromagnetic fields in your home/work (prioritize lowering exposure in the bedroom first)
  • Methylation support:
    • Vitamin B12: I prefer hydroxycobalamin over methylcobalamin, though
    • Methlated folate
    • Riboflavin
    • Vitamin B6
    • Betaine TMG
    • Choline 
    • Creatine, particularly around exercise
  • Skullcap (baicalin): Chinese or American; particularly good for sleep, anxiety, and lowering inflammation 
  • Boswellia (anti-inflammatory)
  • Glutathione support (e.g. NAC, glycine)
  • Magnesium (glycine, threonine, taurine): Many need up to 1000mg or more
  • Probiotics, sometimes high dose if tolerated (particularly those that don’t contribute to histamine, such as those found in ProBiota HistaminX, from Seeking Health)
  • DAO Enzymes to help breakdown histamine from food; can also use desiccated kidney supplements in place of this, such as Heart & Soil or Ancestral Supplements
  • Vitamin D3/K2
  • Vitamin A (retinoid form)
  • Probiotics
    • L. rhamnosus
    • Spore based
  • Peptides
    • BPC157 (great for the gut, collagen e.g. in EDS)
    • Thymosin (appears to be particularly helpful for immune balance)
    • KPV (appears to help mast cells in particular)
  • Off-label use of prescription hydroxyurea (for those with bone pain)

Bodywork and alternative therapies (particularly helpful for supporting vagus nerve)

  • Functional neurology
  • Lymphatic drainage (massage, vibration plate, dry brushing, jumping on rebounder)
  • Fascial counterstain
  • Qigong, Tai Chi
  • Somatic experiencing to work through trauma (body physically holds onto trauma)
  • Visual therapy
  • Craniosacral work
  • Osteopathic manipulation
  • Gentle chiropractic care (no forceful adjustments), e.g. Network, Blaire technique, NUCCA
  • Coffee enemas


According to Dr. Lawrence Afrin, MCAS is likely under-diagnosed and more prevalent than we originally thought – up to 17% of the population in America may have it.  Addressing MCAS takes time, patience, and work, but feeling better is possible!

With my personal experience, and to echo the words of Dr. Neil Nathan, MCAS is a “consequence” of another issue (not an isolated symptom).  There are treatments for support, but addressing the nervous system via the limbic system (involved in any sensitivity, and the emotional response to illness) and vagus nerve (key part of the “rest and digest” nervous system) are key aspects of treatment that cannot be skipped (but do take work!).  Essentially, these set the body up to receive treatment by telling the body that it’s “safe” to take.  And I’ve even seen people heal completely just with these programs!

At the end of the day, however, a diagnosis is just a label that should guide treatments. If the questionnaire suggests MCAS, talk to a knowledgeable healthcare practitioner about treatment options. There aren’t many in mainstream medicine, but they may help!  

If you want personalized guidance for treatment while also looking for the suspected causes, I highly recommend seeking the guidance of a functional medicine professional.  Beyond myself and my colleagues at Parsley Health, I’ve provided a few people below who may have additional educational resources or who may be a good practitioner to work with one-on-one.

Want to work with me? Find me at Parsley Health!

Megan McElroy
Megan McElroy
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