Mast Cell Activation Syndrome (MCAS)-Beyond Just Seasonal Allergies

Beyond Seasonal Allergies

Many of us are already familiar with the effects of histamine on our respiratory tracts. This is particularly evident during allergy season when we may get watery itchy eyes, runny noses, and flares of asthma. Histamine is just one of a thousand of mediators that is released from mast cells causing allergy symptoms. But did you know mast cells can cause continual allergic type reactions, or continue histamine release, without a provoking allergen? This condition is known Mast Cell Activation Syndrome (MCAS) and is much more common in chronic and recurrent symptoms than once thought.

Mast Cell Activation Syndrome

Mast Cell Activation Syndrome can cause an extremely wide expression of various illnesses. Depending on where these mast cells are activated determines the type of symptoms one may have.

Mast cells are immune cells that are present in connective tissues throughout our entire body, not just in our respiratory tract. They are especially abundant beneath environmentally exposed mucosal surfaces and nearby blood and lymphatic vessels and nerves, waiting and watching. In addition to histamine, they release multiple mediators such as proteases, prostanoids, leukotrienes, heparin, and many cytokines, chemokines, and growth factors. These mediators are essential to fighting infections, healing wounds and neutralizing toxins but when they get released inappropriately, they can wreak havoc on our bodies and cause symptoms in any organ system they are activated.

Mast Cell Activation Symptoms

Mast Cell Activation Syndrome can cause an extremely wide expression of various illnesses. Depending on where these mast cells are activated determines the type of symptoms one may have. Below is a list of presentations depending on which organ systems are affected.

  • Head/eyes/ears/throat
    • irritated eyes, episodic inability to focus vision, blepharospasm
    • itchy ears, hearing deficit and or tinnitus
    • irritated nose, sores, nose bleeds
    • burning tongue, trouble swallowing, throat irritation, persistent or intermittent non-painful sensation of a lump or foreign body in the throat,
  • Pulmonary
    • Waxing/waning cough
    • can’t catch a deep breath
  • Cardiovascular
    • Unprovoked fainting or near fainting, erratic blood pressure and pulse, palpitations
    • Chest pain even though no coronary artery disease is found
    • Takotsubo Syndrome(acute balloon congestive heart failure), Kounis Syndrome (allergic angina)
  • Gastrointestinal
    • Inflammation
    • Refractory reflux, irritable bowel syndrome, mild ­elevation in liver enzymes
    • Diarrhea and or constipation
    • Queasiness, nausea, vomiting (sometimes “cyclical”)
    • Malabsorption common (general or selected micronutrients)
  • Genitourinary
    • interstitial cystitis
    • infertility
    • painful periods, heavy periods
  • Musculoskeletal and Joints
    • inflammation of muscles, joint pain, osteopenia
    • fibromyalgia type pain
    • osteopenia and osteoporosis
  • Skin/Integument
    • Lesions (many types), rashes (many types, often migratory), itching, flushing, angioedema, dermatographism (can “write” or scratch a word in your skin and it will become red and raised)
    • Hair/nail/dental abnormalities
  • Nervous system
    • Headache, vertigo, syncope, tic/tremor, weakness, dysautonomia
    • Migratory skin sensations
    • insomnia
    • Wide range of psychiatric disorders
  • Endocrinologic/metabolic
    • Hypo/hyperthyroidism, hyperferritinemia (inflammatory)
    • Growth/Development
      • Poor healing
      • Cysts, fibrosis, endometriosis, vascular anomalies, cancer
      • Connective tissue weakness (e.g., hypermobile Ehlers Danlos Syndrome)

These symptoms can wax and wane where patients may have chronic low-level symptoms with episodic flares. Typically, patients will have a history of being extremely sensitive to medications and supplements due to reactions to various excipients.

Chronic Illness or MCAS?

Many of these symptoms are similar to other chronic illnesses such as toxic mold exposure, persistent tick-borne infections, chronic fatigue syndrome or now long haul COVID. The unifying factor may be the actions of mast cells. If the mast cells increase in number and develop multiple mutations that cause continual release of mediator’s patients could develop these symptoms.

How to Test for MCAS

How do we determine whether patients have MCAS? There are lab tests that measure the various mediators, but it is extremely difficult to capture them accurately as most labs are not equipped to process them properly. If you have had any tissue biopsies in your life and these biopsies are still accessible, you can request a specific stain called CD117/CD25 that will show how many mast cells are in each high powered field.

Because of this, we rely heavily on a patient’s history and exam. It is essential to take a patient’s history that goes back to their mother’s pregnancy and document any history food sensitivities, rashes and other symptoms related to activated mast cells. We review a full family history especially for allergies, autoimmune diseases, and neurological disorders. We administer a MCAS questionnaire which can highlight various symptoms.

How To Treat MCAS

Treatment involves identifying triggers and avoiding them. Keeping a diary of every reaction and every new medicine or supplement you try is very helpful. It is essential to start with one supplement or medication at a time to make sure you don’t have a reaction. For super sensitive patients they should only use single ingredient supplements. Every patient with MCAS will respond differently.

Natural Anti-histamines & Mast Cell Stabilizers

Depending on the severity of your symptoms you can start with natural sources of antihistamines and mast cell stabilizers such as those listed below

    • Vitamin C
    • Vitamin D
    • Alpha lipoic acid
    • N-acetylcysteine
    • Palmitoylethanolamide (PEA)
    • Cannabidiol (CBD)
    • Flavonoids (e.g., quercetin, luteolin, ruten)
    • Stilbenoids (e.g., resveratrol)
    • Alkaloids (e.g., berberine)
    • Lion’s mane
    • Elderberry
    • Omega-3 essential fatty acids/resolvins
    • White willow bark
    • Turmeric/curcumin
    • Green tea
    • Pycnogenol
    • Boswellia
    • Cat’s claw
    • Capsaicin
    • Ginseng

Prescription Medicines

For many patients the above list will be helpful but not enough to control symptoms. To further inhibit mediator production and release, we must rely on antihistamines that block the H1 and H2 receptors. There are other medications that block or inhibit other mast cell mediators as well. The list below is just a small example of what can help. There are hundreds of medications that can be used for this purpose.

  • H1 receptor blockers
    • sedating-helpful for those with insomnia as well
      • diphenhydramine
      • hydroxyzine
      • ketotifen
    • non-sedating
      • loratidine
      • fexofenadine
      • cetirizine
  • H2 receptor blockers
    • famotidine
    • ranitidine
  • Leukotriene inhibitors
    • Montelukast
  • Mast cell stabilizer
    • cromolyn sulfate as a nasal spray, nebulized or orally
  • Miscellaneius
    • low dose naltrexone

Unfortunately, there isn’t an easy way to know which will be most effective. Patients must go through a trial of each medication at various doses over a course of 2 weeks to determine which one(s) stabilize their mast cells the best.

Diet and MCAS

Many patients ask about what role diet plays in MCAS. If you Google “high histamine foods”, you will find many lists that may conflict with each other. We see many patients start to restrict foods until they are down to eating 1-3 types of foods. In general, we advise avoid eating aged meats and leftovers of meats as histamine levels rise when animal protein breaks down. Try to avoid the highest histamine foods, rotate your meals and add herbs that help lower histamine such as ginger, basil, chives, oregano, garlic, peppermint and rosemary. You can help reduce the histamine in your gut by taking the enzyme diamine oxidase (DAO) or the probiotic l. rhamnosus. (be careful with most high dose probiotics). If you want to do more with your diet you can get more ideas from, The 4-Phase Histamine Reset Plan: Getting to the Root of Migraines, Eczema, Vertigo, Allergies and More by Dr. Becky Campbell.

Beyond Medications and Supplements

At Holistique we also utilize multiple other therapies to support our patients with MCAS

  • Low dose Immunotherapy (LDI)
  • Supportive oligonucleotide therapy to address chronic infections
  • Weber Laser
  • IV Nutritional therapies
  • Hyperbaric Oxygen Therapy
  • Ondamed therapy
  • Homeopathy
  • Acupuncture
  • Ozone therapy

Treat the Root Cause of MCAS

Beyond just stabilizing mast cells, we believe that it is essential to identify the cause of the mast cell activation. At Holistique, our providers identify and address root causes such as chronic infections, implants, and toxins. Many times, by removing these triggers, mast cells will calm down thereby reducing symptoms. It is essential though, once you have been identified as having MCAS, that you are always aware of this risk during stressful times such as surgeries, extreme life changes and unexpected exposures. You may need to “dial up” your mast cell stabilizers to avoid an exacerbation.

Mind Body Connection

It is also essential that we address the mind body connection. When we have a history of severe and or chronic reactions, we can develop a “loop” of thinking where whenever we see that trigger, ie, mold or pollen that we assume we are going to have another severe reaction. While this may be true, our minds may amplify the reactivity through the sympathetic nervous system. Utilizing programs such as Dynamic Neural Retraining ( or the Gupta Program ( we can retrain our brains to not react. These types of programs alone have been lifesaving for many.


For those suffering from chronic illnesses that are not getting better despite receiving the best care, you may want to consider whether MCAS is at the root of your illness. We find that patients who don’t respond to any appropriate treatments or are so sensitive they can’t tolerate any treatment for their disease, most likely suffer from MCAS. We find if we address MCAS, patients will feel better just with this treatment alone and will go on to tolerate the treatments they need.

Successful treatment of MCAS, involves having a team of practitioners who believe in you and are willing to collaborate and advocate on your behalf. They must be persistent in their desire to find the answers for your unique presentation.


Kalesnikoff J, Galli SJ.  New developments in mast cell biology.  Nature Immunology 2008;9:1215-23.

Ribatti D.  The development of human mast cells: an historical reappraisal.  Exp Cell Res 2016;342(2):210-5.

Krystel-Whittemore M, Dileepan K and Wood J. Mast Cell: A Multi-Functional Master Cell. Front. Immunol., 06 January 2016 |

Kara Nakisbendi, MD

Dr. Kara Nakisbendi is a board-certified Obstetrician-Gynecologist and Certified Functional Medicine Provider. She received her Bachelor of Science in Biochemistry from Temple University and her Medical Degree from Temple University School of Medicine where she was inducted into the Alpha Omega Alpha Medical Honor Society.

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