What is Mast Cell Activation Syndrome (MCAS)?

You may have heard about mast cells recently.

Since long COVID has now been affecting people for 5 years, there has been more awareness on chronic disease.

This has included Mast Cell Activation Syndrome (MCAS). In fact, COVID infections are associated with increased mast cell release.

Some researchers have even hypothesized that COVID-19 infections may have triggered undiagnosed pre-existing MCAS or overactivation of MCAS in normal folks (Batiha, et al, 2022). This is an area of ongoing research.

What are mast cells?

Mast cells are white blood cells made in the bone marrow that live within connective tissue.

They are found near the endings of nerves and blood vessels, such as in the digestive tract, lungs, mouth, skin and sinuses, among others.

Mast cells carry mediators like histamine, heparin, proteases, leukotrienes, cytokines and more to stand guard against invaders. These mediators are extremely important for protecting our bodies from attack from an allergen, virus, parasite or bacteria.

When attacked, your immune system sends the signal to mast cells through immunoglobulin E (IgE) and non-IgE pathways that you are in danger.

Mast cells are firefighters.

In normal functioning folks, they break down and release mediators, in a process called degranulation, to protect the body. The release of these mediators helps fight the invader and recruit other additional cells to the area and help the body fight the invader.

What happens when mast cell degranulation goes awry?

MCAS, or Mast Cell Activation Syndrome, is one of many Mast Cell Diseases (MCD). Other MCDs include Hereditary Alpha Tryptasemia (HAT), Mast Cell Leukemias and systemic mastocytosis.

In one study, prevalence of MCD as reported through symptom self-report, was found to be present in 17% of a German population (Moulderlings, et al, 2013).

MCAS is a disease in which mast cells degranulate without any attack present, in an ongoing and excessive way (Valent et. al, 2012).

When someone has MCAS, they experience physiologic responses to many internal and external triggers like (but not limited to):

• Food & drink

• Medications

• Dyes

• Temperture

• Stress

• Undernutrition

• Sun

• Hormone changes

• Alcohol

• Odors/Scents

• Infection

• Exercise

• Vibration

• Mold

The reaction someone with MCAS has to stimulus leads to chronic inflammation and a range of symptoms. It can be very debilitating, and decrease daily quality of life.

What are the symptoms of MCAS?

Symptoms of MCAS can involve every organ system, and they always involve at least two.

People with MCAS present with different and similar symptoms (Akin et al., 2010; Valent et al., 2022). I have not found any two cases exactly the same, although there are overlaps.

Some people develop symptoms around puberty, when hormones change. Mast cells have receptors for estrogen and progesterone, so puberty may be an activation event for some people to develop MCAS.

Many people with MCAS have symptoms that include (but are not limited to):

• Flushing

• Unexpected fluctuation in blood pressure

• Itching

• Chronic fatigue

• Chest pain

• Brain fog

• Difficulty breathing

• Headache

• Rashes, especially after using certain creams, band aids or other contacts with skin

• Nausea, vomiting

• Constipation, bloating, diarrhea

• Recurrent or persistent Small Intestine Bacterial Overgrowth (SIBO- LINK to past blog)

• Poor healing (i.e. after a dental visit or a cut)

Some of these symptoms overlap with symptoms of POTS and Ehlers-Danlos syndrome. Indeed, some people with MCAS have all three of these diagnoses. Research is being done to understand how these diagnoses all overlap.

Further, it has been shown that those with MCAS are more likely to also be diagnosed with a psychiatric condition and that MCAS treatment can improve those conditions as well (Weinstock, et al. 2025).

How is MCAS diagnosed?

Before discussing diagnosis, it is important to note that not many providers know about MCAS or believe in its existence. This has been attributed to provider burn out, lack of education and the fact that no specific blood work or diagnostic test to confirm it (Gaudiani, 2025).

There are two schools of thought around MCAS diagnosis (Afrin, et al, 2021). Consensus 1 and Consensus 2.

There are doctors who follow the Consensus-1 rules, which are characterized by:

• Typical clinical signs of severe, recurrent mast cell activation, often with anaphylaxis.

• Proof of mast cell involvement with biochemical studies like serum tryptase, which must increase a certain rate within 4 hours of a symptomatic period.

• Response to treatment

However, Consensus-1 criteria is criticized for missing a large portion of those with MCAS.

Consensus-2 is a bit more flexible and less specific for diagnosis. Chronic symptoms of pathologically increased mast cell activity is the main criterion for Consensus-2.

Minor criteria of consensus-2 include positive lab results (i.e. of mediators like histamine in urine or blood), genetic testing results, mast cell presence in the GI tract upon biopsy, improved symptoms with treatment and/or no alternative diagnosis possible. Presence of one or more these criteria warrants an MCAS diagnosis.

An expert allergist, plus often times a dermatologist and/or gastroenterologist is needed to assess someone and make appropriate diagnosis.

You can read more about the difference in consensus criteria here.

What is the treatment for MCAS?

There are medical, psychological, nutritional and lifestyle treatments that can be utilized for treatment of MCAS.

The main goals of treatment are trigger avoidance and reducing the breakdown of mast cells.

This can be done with:

• Environmental changes with regard to soaps used, artificial dyes consumed, mold remediation and more

• Medication management

• Nutritional & lifestyle considerations

To learn more about medication, Dr Jennifer Gaudiani has a blog series with information. Medications like histamine blockers, leukotriene blockers and mast cell stabilizers are often used alongside many other medications that target both how mast cells break apart and the effects of this degranulation.

Glucagon-like peptide-1 is also being explored to see if it potentially helps people with MCAS, after a recent case study was published (Afrin, et al. 2025). More to come here, with of course, considerable complexity.

As a dietitian, I can support clients in supporting trigger avoidance and nutritional management.

This may include:

• Keeping a cold vest around during hotter weather

• Working on stress reduction

• Ensuring adequate food intake, since chronic undernourishment can trigger MCAS

• Trying supplements like quercetin to stabilize mast cells or other supplements like luteolin that may have beneficial effects on symptoms

• Getting rid of all scented candles, soaps, detergents, cleaners, etc.

• Repleting any vitamins or minerals that someone is deficient in

• Advocating for clients to get nutritional labs and medical testing done

It is not best practice to give people with MCAS a low histamine diet or restrict the diet. Not only is the low histamine diet not a standardized diet, but many people react differently to the same foods (Harris, Nassar & Finnerty, 2024).

The ‘food prescription’ needs to be individualized.

Working with clients 1:1 is the best way to understand what foods may cause issues, if any. Some clients may benefit from reducing certain foods in the diet. For instance, gluten-free diets have worked to reduce symptoms in some of my clients and there is some literature to back this up, but it is not recommended for all.

Remember, whenever we cut something out, there are potential negative consequences like micronutrient deficiencies or microbiome changes.

Generally, it is helpful to include the most foods possible in the diet, eat enough food, manage symptoms of any food intolerances and restrict only the foods necessary.

The MCAS care in Germany is limited, and there are some communities forming to fill the gap.   Mastozytose is one such organization that can help you find the support you need.

How do eating disorders and MCAS intersect?

There is overlap between MCAS and eating disorders. Further, these diagnoses may also intersect in individuals with POTS and Ehlers-Danlos syndrome as well.

For instance, someone may start going through puberty and develop MCAS symptoms that then lead to food restriction to manage, which then leads to eating disorder development. Alternatively, an eating disorder may be present and as MCAS develops, become exacerbated.

If you’re struggling with an eating disorder and MCAS, it is important to work with specialists who can support your individual needs and help you reduce the symptoms of both at the same time.

Moving forward

MCAS research is growing, with more awareness and desires for more treatments to help people gain more control of their symptoms.

MCAS is real and if you have it, or suspect you may, you can get help finding the right combination of symptom-targeted medication, trigger understanding and supportive care.

If you are interested in understanding what MCAS treatment can look like for you, book a free intro call with me here.

References:

Afrin, L., Ackerley, M., Bluestein, L., Brewer, J., Brook, J., Buchanan, A., Cuni, J., Davey, W., Dempsey, T., Dorff, S., Dubravec, M., Guggenheim, A., Hindman, K., Hoffman, B., Kaufman, D., Kratzer, S., Lee, T., Marantz, M., Maxwell, A., McCann, K., McKee, D., Menk Otto, L., Pace, L., Perkins, D., Radovsky, L., Raleigh, M., Rapaport, S., Reinhold, E., Renneker, M., Robinson, W., Roland, A., Rosenbloom, E., Rowe, P., Ruhoy, I., Saperstein, D., Schlosser, D., Schofield, J., Settle, J., Weinstock, L., Wengenroth, M., Westaway, M., Xi, S. & Molderings, G. (2021). Diagnosis of mast cell activation syndrome: a global “consensus-2”. Diagnosis, 8(2), 137-152. https://doi.org/10.1515/dx-2020-0005

Afrin LB, Weinstock LB, Dempsey TT, Aschenbrenner K, Blitshteyn S, Schofield JR. Utility of glucagon-like-peptide-1-receptor agonists in mast cell activation syndrome. Am J Med Sci. 2025 Oct;370(4):377-382. doi: 10.1016/j.amjms.2025.07.006. Epub 2025 Jul 15. PMID: 40675372.

Akin C, Valent P, Metcalfe DD. Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol. 2010;126(6):1099-104 e4.

ASCIA. (2025). ASCIA position paper – Diagnosis and investigation of mast cell activation disorders and syndrome. ASCIA. https://www.allergy.org.au/images/stories/pospapers/ASCIA_HP_Mast_Cell_Disorders_2025.pdf

Batiha, G. E., Al-Kuraishy, H. M., Al-Gareeb, A. I., & Welson, N. N. (2022). Pathophysiology of Post-COVID syndromes: a new perspective. Virology journal, 19(1), 158. https://doi.org/10.1186/s12985-022-01891-2

Gaudiani, J. L. (2022, July 21). Mast cell activation syndrome (MCAS) & eating disorders | Part one: What is MCAS, and why should clinicians and people with eating disorders care? Gaudiani Clinic. https://www.gaudianiclinic.com/gaudiani-clinic-blog/2022/7/21/mast-cell-activation-syndrome-mcas-amp-eating-disorders-part-one-what-is-mcas-and-why-should-people-with-eating-disorders-care

Gaudiani, J. Sick Enough, 2nd edition.

Harris, C. I., Nasar, B., & Finnerty, C. C. (2024). Nutritional Implications of Mast Cell Diseases. Journal of the Academy of Nutrition and Dietetics, 124(11), 1387–1396. https://doi.org/10.1016/j.jand.2024.05.008

Harris, C. MCAD & POTS. Presented May 1, 2025. 

Harris, D. (2024, October). MCAS testing and diagnosis: Consensus 1 vs. consensus 2. The EDS Clinic. https://www.eds.clinic/articles/mcas-testing-and-diagnosis-consensus-1-vs-consensus-2

Meneses-Preza, Y. G., Soria-Castro, R., Alfaro-Doblado, Á. R., Hernández-Solis, A., Álvarez-Maldonado, P., Gómez-Martín, D., Torres-Ruiz, J., Muñoz-Valle, J. F., Muñoz-Ríos, G., Hernández-Ramírez, C. O., Güemes-González, A. M., Wong-Baeza, I., Maravillas-Montero, J. L., Pérez-Tapia, S. M., Chávez-Blanco, A. D., Estrada-Parra, S., & Chacón-Salinas, R. (2025). Mast cell activation signature as a potential biomarker in COVID-19. Immunology Letters, 275, 107026. https://doi.org/10.1016/j.imlet.2025.107026

Molderings, G. J., Haenisch, B., Bogdanow, M., Fimmers, R., & Nöthen, M. M. (2013). Familial occurrence of systemic mast cell activation disease. PloS one, 8(9), e76241. https://doi.org/10.1371/journal.pone.0076241

Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215–25.

Valent P, Hartmann K, Bonadonna P, Gulen T, Brockow K, Alvarez-Twose I, et al. Global classification of mast cell activation disorders: an ICD-10-CM-adjusted proposal of the ECNM-AIM consortium. J Allergy Clin Immunol Pract. 2022;10(8):1941–50.

Weinstock LB, Afrin LB, Reiersen AM, Brook J, Blitshteyn S, Ehrlich G, Schofield JR, Kinsella L, Kaufman D, Dempsey T, Molderings GJ. Prevalence and treatment response of neuropsychiatric disorders in mast cell activation syndrome. Brain Behav Immun Health. 2025 Jun 30;48:101048. doi: 10.1016/j.bbih.2025.101048. PMID: 40686928; PMCID: PMC12270938.

Zha K, Brook J, McLaughlin A, Blitshteyn S. Gluten-free diet in postural orthostatic tachycardia syndrome (POTS). Chronic Illn. 2023 Jun;19(2):409-417. doi: 10.1177/17423953221076984. Epub 2022 Jan 31. PMID: 35098721.