Mast Cell Activation

June 20, 2023
Mast Cell Activation


Does mast cell activation and release occur in non-atopic food intolerance? What is the evidence, for and against?


From the Editor: It appears that non IgE- mediated food mechanisms do not involve mast cell activation, except for the possibility in the spectrum of systemic mastocytosis.


By Dr. Iris E. Hidalgo Nicho

irst, it is necessary to clarify that the diagnosis of “food intolerance” can include a wide spectrum of clinical manifestations related to food intake, from lactose intolerance due to lactase deficiency to gluten enteropathy due to a non-IgE mediated immune reaction.

The National Health Service (NHS) of the United Kingdom, defines food intolerance “when you have difficulty digesting certain foods or ingredients in food”, clearly stating that it is not a food allergy (

Therefore, by definition, mast cell activation and release are not involved in non-atopic food intolerance. However, in pathologic “hyperactive” mast cell conditions, such as systemic mastocytosis or inflammatory bowel disease, clinical symptoms of mast cell release could be triggered by food molecules -and other diverse stimuli too- in the absence of IgE-mediated mechanisms. Although gut mast cells could be activated by lectins in raw potatoes and agglutinins from uncooked red kidney beans, the underlying pathophysiological mechanism is not yet understood.

Furthermore, recent studies show that after infectious gastroenteritis, mast cells in the murine gut can react to food given at the time of infection. More recently, mast cells have been found to express MRGPRX2 receptors, which can be activated through non-IgE pathways by small molecules such as icatibant, quinolones, and neuromuscular blocking agents.



  • Weinstock, Leonard B et al. “Mast Cell Activation Syndrome: A Primer for the Gastroenterologist.” Digestive diseases and sciences vol. 66,4 (2021): 965-982. doi:10.1007/s10620-020-06264-9
  • Weiler, Catherine R. “Mast Cell Activation Syndrome: Tools for Diagnosis and Differential Diagnosis.” The journal of allergy and clinical immunology. In practice vol. 8,2 (2020): 498-506. doi:10.1016/j.jaip.2019.08.022
  • Afrin, Lawrence B et al. “Diagnosis of mast cell activation syndrome: a global "consensus-2".” Diagnosis (Berlin, Germany) vol. 8,2 137-152. 22 Apr. 2020, doi:10.1515/dx-2020-0005
  • Valent, Peter et al. “Proposed Diagnostic Algorithm for Patients with Suspected Mast Cell Activation Syndrome.” The journal of allergy and clinical immunology. In practice vol. 7,4 (2019): 1125-1133.e1. doi:10.1016/j.jaip.2019.01.006
  • Valent, Peter et al. “Diagnosis, Classification and Management of Mast Cell Activation Syndromes (MCAS) in the Era of Personalized Medicine.” International journal of molecular sciences vol. 21,23 9030. 27 Nov. 2020, doi:10.3390/ijms21239030
  • Spiller, Robin. “Impact of Diet on Symptoms of the Irritable Bowel Syndrome.” Nutrients vol. 13,2 575. 9 Feb. 2021, doi:10.3390/nu13020575 Food intolerance. Available in:

Iris E. Hidalgo Nicho, MD
Allergy and Immunology
Hospital Nacional Edgardo Rebagliati Martins
Lima, Peru


By Dr Lawrence Schwartz

I am not aware of foods triggering mast cell activation in a non-atopic or IgE-independent manner - unlike for certain drugs, such as vancomycin and morphine, which do directly activate mast cells in an IgE/FcERI-independent manner.

Lawrence B. Schwartz, MD, PhD
Charles & Evelyn Thomas Professor of Medicine
Chair, Division of Rheumatology, Allergy & Immunology
Richmond, Virginia, USA


By Dr Mariana Castells

There is indirect evidence through the measurement of mast cell mediators that GI mast cells can be activated by certain foods in patient with mastocytosis and MCAS. In non mastocytosis patients there is no evidence of mast cell activation in Food intolerance which has a wide definition: from lactose intolerance which does not involve mast cell activation and is the result of lactase deficiency to gluten enteropathy which is an IgG mediated immune reaction. 

Mariana C. Castells, MD, PhD
Associate Physician, Department of Medicine, Rheumatology and Immunology
Brigham and Women’s Hospital
Associate Professor of Medicine, Harvard Medical School
Boston, Massachusetts, USA


Back to Question & Answer list