An Overview of the Symptoms, Triggers, and Treatments for Mast Cell Activation Syndrome

Our bodies are constantly bombarded with allergens, bringing with them the dreaded allergy symptoms – sneezing, runny nose, watery eyes, and itchy skin.

Interestingly, those symptoms are our body’s way of protecting us from the irritant or trauma that we’re experiencing. The sneezing or runny nose is our immune system’s response from our mast cells telling us that we have a problem. And, yes, we consider this a positive response.

But, when our body overreacts, it can cascade into unexplained symptoms throughout the body. This condition of hypersensitive mast cells overreacting to things that we should tolerate could be  mast cell activation syndrome.

Let’s dive into what exactly mast cell activation syndrome is, how it might be causing your symptoms, and what you can do about it.


What are mast cells?

Mast cells, a type of white blood cell found in connective tissues throughout the body, play critical roles in the body’s wound healing, defense against pathogens, and regulation of the immune system.[1]

Mast cells have receptors on their surface that recognize various stimuli, including allergens, toxins, and infectious agents. When these receptors are activated, mast cells release various chemical mediators, which can have both protective and potentially harmful effects on the body.[2]


woman thinking about mast cell activation syndrome

What is mast cell activation syndrome?

Mast Cell Activation Syndrome (MCAS) is an immune disorder where mast cells become overactive and malfunction, releasing excessive inflammatory chemicals in response to triggers that generally would not cause a reaction.[3]

When your body is exposed to a perceived threat, your overactive mast cells go bonkers. They begin secreting large amounts of chemical mediators in a process known as degranulation to protect you from the threat. Instead, this protective response from your mast cells triggers adverse local and systemic effects, leading to multiple allergic and inflammatory symptoms in multiple systems of the body

The normal immune system response that degranulation causes are typically positive. We need our mast cells to respond to a threat, like a virus. However, when triggered too frequently or too easily, it results in mast cell activation syndrome, which triggers a wide range of symptoms that can affect nearly the entire body. [4]

Mast Cell Activation Syndrome vs. Mastocytosis

MCAS and mastocytosis are two distinct conditions involving abnormal mast cells.

Mastocytosis is a rare disease characterized by an abnormal accumulation of mast cells in various body tissues, including the skin, bone marrow, and gastrointestinal tract.[5] In contrast to mastocytosis, MCAS does not involve a significant increase in the number of mast cells in the body. Instead, it is characterized by abnormal activation of the mast cells that occur even in the absence of a trigger.


Chemical Mediators and Mast Cell Activation Syndrome

Chemical mediators are substances released by cells in the body in response to stimuli or triggers and can influence or regulate the function of other cells or tissues.

In MCAS, various triggers can abnormally activate mast cells, including certain foods, medications, chemicals, infections, and stress. Leading to the release of a variety of chemical mediators, including: [6]

  • Histamine
  • Heparin
  • Tryptase
  • Chymase
  • Interleukins
  • Prostaglandins
  • Cytokines
  • Chemokine
  • Proteases

These chemical mediators play a vital role in the body’s natural inflammatory response by helping to dilate blood vessels so that immune cells can migrate to the infection site or injury to begin helping the body heal. Externally, this looks a lot like the early stages of an allergic reaction.


woman with fatigue from MCAS

Signs and Symptoms of Mast Cell Activation Syndrome

The symptoms of MCAS vary widely from person to person. This is one of the reasons that it is often difficult for clinicians to recognize. It can look so different between individuals. The constellation of symptoms may depend on a variety of different factors, what triggers involve which tissues in the body, and which mediators are present in the mast cells. All these factors can radically change the collection of symptoms someone with MCAS may have. To complicate matters even more, these symptoms are often waxing and waning AND migratory.

Symptoms of MCAS include: [7]

  • Hives, rashes, itching, or flushing skin, dermatographism
  • Abdominal pain, cramping, bloating, diarrhea, constipation, and nausea
  • Wheezing, shortness of breath, allergy symptoms, itchy eyes, runny nose, congestion
  • Low blood pressure, rapid heartbeat or palpitations, chest pain, Postural orthostatic tachycardia syndrome (POTS)
  • Headaches, migraines, or neuropathy
  • Brain fog
  • Dizziness
  • Fatigue
  • Joint and muscle pain
  • Menstrual irregularities, endometriosis
  • Interstitial cystitis
  • Hot flashes and night sweats
  • Anxiety, irritability, or depression

There are also several conditions associated with MCAS, though it can be hard to determine how they are related. Conditions commonly associated with MCAS include: [8]

  • Chronic Lyme disease
  • Fibromyalgia
  • Hypercoagulation
  • Irritable Bowel Syndrome (IBS)
  • Small Intestine Bacterial Overgrowth (SIBO)
  • Mold toxin illness
  • Ehlers-Danlos hypermobility
  • Autoimmune conditions
  • Multiple chemical sensitivity
  • POTS


woman tired after excercise

Triggers and Causes of Mast Cell Activation Syndrome

The exact trigger of MCAS can vary from person to person, but some common triggers include the following:

  • Certain foods
  • Physical activity
  • Stress
  • Changes in temperature
  • Alcohol
  • Hormonal changes
  • Odors
  • Medications
  • Infections
  • Chemical toxicants

The exact causes of MCAS are not yet fully understood, and additional research is needed. However, several factors have been identified that may contribute to the development of the condition, including:

  1. Genetics. There may be a genetic predisposition to MCAS, as it can run in families.[9] Mutations are often found in somatic genes, not germ cell lines. Despite this, current estimates state that roughly 17% of the population have MCAS.
  2. Environmental factors: Exposure to certain environmental toxins, pollutants, and chemicals can trigger MCAS.
  3. Infections: Certain infections, such as Lyme disease, Epstein-Barr virus, and long-haul COVID, have been linked to MCAS.[10] Chronic infections can also lead to persistent inflammation and immune system activation, which may contribute to the development of MCAS.[11]
  4. Other medical conditions. MCAS can also occur due to other medical conditions, such as autoimmune diseases, chronic inflammatory disorders, and cancer.[12]
  5. Medications. Certain medications, such as opioids, antibiotics, and nonsteroidal anti-inflammatory drugs (NSAIDs), can trigger MCAS.[13] [14]
  6. Hormonal changes. Hormonal changes during menstruation or menopause can also trigger MCAS.[15]
  7. Allergies: Chronic exposure to allergens can lead to symptoms of MCAS.[16]
  8. Mold and mycotoxin exposure. Although the literature is limited, in my clinical experience, this is one of the most common triggers of MCAS.

The triggers and causes of MCAS vary from person to person, and the condition can have multiple contributing factors. Identifying the underlying causes of MCAS is essential for developing an effective treatment plan.


How is mast cell activation syndrome diagnosed?

There are currently no universally accepted diagnostic criteria for MCAS, and diagnosis is often based on a combination of medical history, clinical presentation, and laboratory testing. However, several proposed criteria have been developed to aid in diagnosing MCAS.

One of the most commonly used diagnostic criteria for MCAS requires the presence of at least two of the following criteria: [17]

  1. Typical symptoms of mast cell activation from two or more organs including flushing, itching, hives, abdominal pain, or diarrhea, among others.
  2. Documentation of elevated mast cell mediators, such as serum tryptase, histamine, or prostaglandin D2 levels.
  3. Primary and secondary disorders, such as mastocytosis or clonal mast cell disease, have been ruled out.
  4. Response to treatment with mast cell stabilizers or antihistamines.

Other proposed diagnostic criteria for MCAS include the “MCAS Diagnostic Score” and the “International Consensus Criteria,” which assigns points based on the presence of symptoms, laboratory findings, and response to treatment.[18] [19]


supplements for treating Mast Cell Activation Syndrome

How is mast cell activation syndrome treated?

There is currently no cure for MCAS, but treatment is available to help manage the symptoms and prevent triggers. Because of the wide range of possible symptoms caused by MCAS, treatment plans are highly individualized based on your symptoms.

I have found that the most effective treatments for MCAS employ a three-prong approach:

  1. Quiet down the mast cells. See below.
  2. Improve the autonomic nervous system through vagus nerve stimulation.
  3. Brain retraining to reduce limbic system activation.  (look forward to blogs on these topics.)

Treatment for quieting MCAS may include the following approaches:

Avoiding triggers.

Identifying and avoiding triggers that can cause mast cell activation is essential to managing MCAS. Eat organic to avoid pesticides. Use clean, unscented personal care and cleaning products. Reduce EMF exposure by turning off wifi and hard-wiring your home.

Identifying root causes and eliminating them.

If mold toxin illness or bartonella infection is a root cause, then identifying and appropriately treating these issues will go a long way to reducing reactivity and restoring health.


There are a wide variety of medications that can be helpful in reducing symptoms, either by stabilizing mast cells or blocking the effects of the mediators.  Antihistamines, such as H1 and H2 blockers, can be immensely useful for many people with MCAS.  Cromolyn and ketotifen, which are mast cell stabilizers, are also very effective.  I also use LDN, Xolair, leukotriene inhibitors, and rarely tyrosine kinase inhibitors have been used to reduce inflammation and prevent mast cell degranulation.

Dietary adjustments.

Some people with MCAS may benefit from a low-histamine diet, especially if they also have histamine intolerance.  Sometimes low oxalate or low salicylate diets are necessary temporarily as well.

Nutraceutical Supplements.

In scouring the medical literature, I identified nearly 65 supplements with some mast cell stabilizing effects!! This is amazing news because it means that so many potentially helpful supplements can help reduce inflammation and support mast cell function, such as Perimine, Pycnogenol, Quercetin, and HistDAO.

Lifestyle changes.

Managing stress, regular exercise, and enough rest can help reduce symptoms and prevent mast cell activation.

Complementary and alternative therapies.

Acupuncture, massage therapy, and other complementary therapies may also help manage symptoms of MCAS.

Address the mind/ emotion/ spirit aspects of your being.

My patients, who are most successful in healing from MCAS, recognize that they must face their traumas, their beliefs about themselves, their boundaries (or lack thereof), and their place in the world to fully heal. This may not be the first step in the healing journey, but it is essential.

Working with a healthcare provider, or even a team, familiar with MCAS is essential to ensure you have an individualized treatment plan based on your symptoms. And keep in mind that you may need to adjust your treatment approach as your symptoms change and improve.


Access The Many Manifestations of Mast Cell Activation Free

Are you ready to dive deeper into mast cell activation?

Get started by accessing The Many Manifestations of Mast Cell Activation, a free online course hosted by Dr. Kelly. Plus, when you sign-up, you’ll get access to several fun bonus gifts, including the Mast Cell Activation Frequently Asked Questions eGuide, the Low Histamine Diet Starter Kit eGuide, and the Many Manifestation of Mast Cell Activation workbook.

Join us on a journey to optimal wellness and gain valuable insight into living your healthiest life!


[1] “Mast Cell: A Multi-Functional Master Cell – Frontiers.” Accessed 13 Mar. 2023.

[2] “Mast cell activation syndrome – About the Disease.” Accessed 13 Mar. 2023.

[3] “Mast Cell Activation Syndrome (MCAS).” Accessed 16 Mar. 2023.

[4] “Mast cell activation syndromes – evaluation of current diagnostic ….” 25 Jun. 2020, Accessed 13 Mar. 2023.

[5] “Mastocytosis – About the Disease.” Accessed 16 Mar. 2023.

[6] “Recent advances in our understanding of mast cell activation – NCBI.” 22 Apr. 2019, Accessed 16 Mar. 2023.

[7] “Mast Cell Activation Syndrome (MCAS).” Accessed 13 Mar. 2023.

[8] “Systemic mast cell activation disease variants and certain ….” Accessed 16 Mar. 2023.

[9] “Systemic mast cell activation disease: the role of molecular genetic ….” Accessed 13 Mar. 2023.

[10] “Mast cell activation symptoms are prevalent in Long-COVID – NCBI.” 23 Sep. 2021, Accessed 13 Mar. 2023.

[11] “Mast Cells and Influenza A Virus: Association with Allergic … – Frontiers.” 1 May. 2015, Accessed 16 Mar. 2023.

[12] “Elevated basal serum tryptase identifies a multisystem disorder ….” Accessed 16 Mar. 2023.

[13] “Opioid-induced mast cell activation and vascular responses is not ….” Accessed 16 Mar. 2023.

[14] “What we know about nonsteroidal anti-inflammatory drug … – NCBI.” 31 Mar. 2016, Accessed 16 Mar. 2023.

[15] “Role of female sex hormones, estradiol and progesterone, in mast ….” 19 Jun. 2012, Accessed 13 Mar. 2023.

[16] “Mast cell activation syndromes presenting as anaphylaxis – PubMed.” Accessed 16 Mar. 2023.

[17] “Environmental mold and mycotoxin exposures elicit specific cytokine ….” 26 May. 2015, Accessed 3 Apr. 2023.

[18] “Diagnosis of mast cell activation syndrome: a global “consensus-2″.” 22 Apr. 2020, Accessed 16 Mar. 2023.

[19] “Proposed Diagnostic Algorithm for Patients with Suspected Mast ….” Accessed 16 Mar. 2023.