Mast cell disorders are a group of immune conditions affecting up to one in three individuals worldwide. In some cases, rare mast cell conditions are only seen in approximately one in 10,000 to 20,000 individuals. (2) These conditions are varied, and symptoms may range from mild, such as hives, nasal congestion, and abdominal cramps, to life-threatening, such as anaphylaxis. (13) Read on to learn about mast cell activation disorders, as well as their triggers, symptoms, and treatment approaches.

What are mast cells?

Mast cells are immune cells involved in allergic responses, wound healing, immune tolerance, and the innate immune response. (4) Mast cells are found throughout areas of the body that are exposed to the environment, such as the skin, eyes, respiratory system, and gastrointestinal system, as well as in the liver, spleen, bone marrow, and lymph nodes. (13)

Mast cells are a type of granulocyte, which means that they release small particles when activated. Particles released from mast cells include arachidonic acid products, biogenic amines, cytokines, growth factors, neuropeptides, and proteolytic enzymes. (15) These substances are released as part of an inflammatory process, in an attempt to protect the body from foreign substances. (6) The cell is activated when immune molecules, bacterial products, (15) allergens or other stimuli are bound to receptors on the mast cell. (4)

close up of person scratching their neck

Symptoms of mast cells activation syndrome may include flushing, nasal congestion, and urticaria (hives). (13)

Mast cell activation disorders

Mast cell activation disorder (MCAD) is an umbrella term used for various conditions that involve excessive mast cell activation in response to a perceived threat, or an abnormally high number of mast cells in the body. (2) These disorders may be categorized as primary (mastocytosis), secondary (reactive), or idiopathic (mast cell activation syndrome). The symptoms seen in these conditions are related to an excessive release of substances from mast cells, particularly the biogenic amine known as histamine. (4)

Mastocytosis

Primary MCADs develop as a result of mutations of a specific gene responsible for regulating mast cell production. (6) Mastocytosis is a primary MCAD and is characterized by an abnormal reproduction of mast cells, which results in an increased number of these cells in several areas of the body, including the bone marrow, skin, and gastrointestinal tract. The most common symptom of mastocytosis is a rash on the skin. (4) In the majority of cases, mastocytosis develops during childhood. (6)

Reactive MCADs

Reactive MCADs, also referred to as secondary MCADs, are the most commonly occurring mast cell conditions. These diseases may be immunoglobulin E-mediated allergic reactions, such as anaphylaxis, or other immune conditions, such as allergic rhinitis, atopic dermatitis, and chronic autoimmune urticaria (hives). (4)

Mast cell activation syndrome

Mast cell activation syndrome (MCAS) is a term that has been used to describe cases in which individuals experience common allergic symptoms with mast cell activation where the cause cannot be identified. To date, the progress and mechanisms of MCAS are not well understood. (1)

Causes and risk factors

Mast cell disorders may occur as a result of molecular, genetic, and chromosomal defects. (12) Mast cell activation may be triggered or exacerbated by several factors, including:

  • Acute or chronic infections (2)
  • Alcohol (6)
  • Certain medications (e.g., nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids) (3)
  • Changes in pH level (acid-base balance) (13)
  • Changes in temperature (13)
  • Emotional stress (13)
  • Certain foods (2)
  • Inhaled triggers (2)
  • Insect bites (3)
  • Pain and pressure (13)
  • Strenuous activity (6)
Young mother feeding her daughter on a bed.

Mast cell disorders may be triggered by certain foods, and their treatment may include a histamine-free diet.

Mast cell activation disorder symptoms and complications

The symptoms of mast cell disorders are varied, and may be localized (restricted to one tissue or area), or systemic. (2) Further, the severity of symptoms may range from mild to severe. (13)

Examples of localized mast cell disorder symptoms include:

  • Allergic rhinitis
  • Urticaria
  • Wheezing (2)

Systemic mast cell disorder symptoms occur in two or more body systems. Examples of systemic symptoms include:

  • Cardiovascular: hypotensive syncope (fainting due to low blood pressure), tachycardia (elevated heart rate) (2)
  • Gastrointestinal: abdominal cramps, diarrhea, nausea, vomiting (2)
  • Naso-ocular: conjunctival injection (enlarged vessels on the eye’s surface), nasal stuffiness, pruritus (severe itching) (2)
  • Respiratory: anaphylaxis, throat swelling, (13) wheezing (2)
  • Skin: angioedema, flushing, urticaria (2)

Research suggests that mast cell activation may also be involved in several inflammatory conditions. (15) For example, accumulation and activation of mast cells in the bladder and prostate have been associated with interstitial cystitis (IC) and chronic prostatitis. In these conditions, stress may trigger mast cell activation. (15)

Additionally, mast cells release a pro-inflammatory compound, interleukin 6 (IL-6), which is elevated in individuals with rheumatoid arthritis. In animal studies, mast cell deficiency in mice was shown to be associated with resistance to certain types of arthritis. Additionally, levels of IL-6 were not increased in these mice following stress. (15) This suggests that mast cells mediators, such as IL-6, may be associated with the development of certain types of arthritis.

Aloe vera plant and aloe pieces on a white table.

Dietary supplements such as Aloe vera may improve symptoms of mast cell disorders.

Mast cell disorder treatment

Integrative treatment of mast cell disorders may involve anti-histamine medication, (4) as well as the lifestyle therapies outlined below.

Stress management

MCADs may be triggered or exacerbated by stress. (13) Mast cell activation may result from stress in a number of conditions, including interstitial cystitis (IC), chronic prostatitis, and arthritis, (15) as well as from stress and brain injury in neurodegenerative conditions such as Alzheimer’s disease. (8) Manage your stress by incorporating mindfulness, yoga, regular exercise, and/or dietary supplements.

Diet

Experimental research suggests that dietary fiber and its metabolites (e.g., short-chain fatty acids (SCFAs)) may regulate mast cell function. (5) Additionally, restricting the intake of certain trigger foods may help to minimize symptoms. According to the Mastocytosis Society, individuals with mast cell disorders may react to certain foods or dietary ingredients, including:

  • Alcohol
  • Artificial flavors
  • Artificial food coloring
  • Chocolate
  • Monosodium glutamate (MSG)
  • Pineapples
  • Preservatives
  • Shellfish
  • Tomatoes and tomato products (14)

A histamine-free diet, which eliminates many of these foods, is commonly recommended for individuals with mast cell activation disorders. The intention of this diet is to minimize dietary sources of histamine that contribute to the overall load of histamine in the body, thereby reducing allergic symptoms. (9)

Dietary supplements

The following table summarizes dietary supplements that may benefit individuals with MCADs.

table summarizing dietary supplements that may benefit individuals with MCADs

Various in vitro and in vivo studies have shown that several dietary supplements may help regulate mast cell activation.

The bottom line

Mast cell disorders are a group of conditions that result from an abnormally high number of mast cells or a disproportionate reaction of these cells to external triggers. These conditions are characterized by a variety of localized or systemic allergic symptoms. Treatment options may involve medication, stress management, nutritional interventions, and dietary supplements. If you suspect you may have a mast cell disorder, speak with your integrative health care provider for guidance.

Fullscript simplifies supplement dispensing.

Create your dispensary today I'm a patient
  1. Akin, C., Valent, P., & Metcalfe, D. D. (2010). Mast cell activation syndrome: Proposed diagnostic criteria. The Journal of Allergy and Clinical Immunology, 126(6), 1099–104.e4.
  2. Akin, C. (2017). Mast cell activation syndromes. Journal of Allergy and Clinical Immunology, 140(2), 349–355.
  3. Bonadonna, P., Pagani, M., Aberer, W., Bilò, M. B., Brockow, K., Elberink, H. O., … Torres, M. J. (2015). Drug hypersensitivity in clonal mast cell disorders: ENDA/EAACI position paper. Allergy, 70(7), 755–763.
  4. Cookson, H., & Grattan, C. (2016). An update on mast cell disorders. Clinical medicine (London, England), 16(6), 580–583. doi:10.7861/clinmedicine.16-6-580
  5. Folkerts, J., Stadhouders, R., Redegeld, F. A., Tam, S. Y., Hendriks, R. W., Galli, S. J., & Maurer, M. (2018). Effect of dietary fiber and metabolites on mast cell activation and mast cell-associated diseases. Frontiers in Immunology, 9, 1067.
  6. Gangireddy, M., & Ciofoaia, G. A. (2019). Systemic mastocytosis. In StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK544345/
  7. Gulledge, T. V., Collette, N. M., Mackey, E., Johnstone, S. E., Moazami, Y., Todd, D. A., … Laster, S. M. (2018). Mast cell degranulation and calcium influx are inhibited by an Echinacea purpurea extract and the alkylamide dodeca-2E,4E-dienoic acid isobutylamide. Journal of Ethnopharmacology, 212, 166–174.
  8. Kempuraj, D., Selvakumar, G. P., Thangavel, R., Ahmed, M. E., Zaheer, S., Raikwar, S. P., … Zaheer, A. (2017). Mast cell activation in brain injury, stress, and post-traumatic stress disorder and Alzheimer’s disease pathogenesis. Frontiers in Neuroscience, 11, 703.
  9. Martin, I. S. M., Brachero, S., & Vilar, E. G. (2016). Histamine intolerance and dietary management: A complete review. Allergologia Et Immunopathologia, 44(5), 475–483.
  10. Safaralizadeh, R., Nourizadeh, M., Zare, A., Kardar, G. A., & Pourpak, Z. (2013). Influence of selenium on mast cell mediator release. Biological Trace Element Research, 154(2), 299–303.
  11. Sanada, S., Kuze, M., & Yoshida, O. (1987). [Beneficial effect of zinc supplementation on pruritus in hemodialysis patients with special reference to changes in serum histamine levels]. Hinyokika Kiyo, 33(12):1955-60.
  12. Silva, I., Carvalho, S., Pinto, P., Machado, S., & Pinto, J. R. (2008). Mastocytosis: A rare case of anaphylaxis in paediatric age and literature review. Allergologia Et Immunopathologia, 36(3), 154–163.
  13. Soderberg, M. L. (2015). The mast cell activation syndrome: A mini review. MOJ Immunology, 2(1).
  14. The Mastocytosis Society. (n.d.). Nutrition. Retrieved from https://tmsforacure.org/nutrition/
  15. Theoharides, T. C., & Bielory, L. (2004). Mast cells and mast cell mediators as targets of dietary supplements. Annals of Allergy, Asthma & Immunology, 93(2).
  16. Wang, X., Ma, D. W., Kang, J. X., & Kulka, M. (2015). n-3 Polyunsaturated fatty acids inhibit Fc ε receptor I-mediated mast cell activation. The Journal of Nutritional Biochemistry, 26(12), 1580–1588.