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Understanding Mast Cell Activation Syndrome (MCAS) and the DAO Gene: A Crucial Connection

Written by Portland Clinic of Natural Health on June 29, 2024

Mast Cell Activation Syndrome (MCAS) is a condition where mast cells, a type of white blood cell involved in our immune response, become overly active. These cells release various chemicals, including histamine, which cause inflammation and allergic reactions. While mast cells usually function properly, in those with MCAS, they can become hypersensitive, leading to symptoms like hives, abdominal pain, headaches, and even anaphylaxis. Managing these symptoms is challenging, especially when environmental factors are at play. (1)

The DAO Gene and Diamine Oxidase Deficiency

The DAO gene, responsible for producing the enzyme diamine oxidase, is crucial in breaking down histamine in the body. Histamine plays a role in immune responses, gut function, and acts as a neurotransmitter. However, for individuals with a DAO deficiency, histamine isn't broken down effectively, leading to its accumulation and exacerbating MCAS symptoms. This genetic predisposition can significantly impact how one reacts to environmental allergens and irritants, making it essential to understand and manage MCAS. (2)

The Overlap of MCAS and DAO Deficiency

In my practice at the Portland Clinic of Natural Health, I frequently see patients where MCAS and DAO deficiency overlap. These patients often have heightened sensitivities to environmental factors like mold, pollutants, and certain foods. By identifying and addressing DAO gene deficiencies, we can create a personalized treatment plan that includes environmental modifications, dietary adjustments, and supplements to support histamine breakdown. This comprehensive approach is vital for achieving long-term results. (3)

MCAS Management and Integrative Medicine

To manage MCAS effectively, it's essential to reduce histamine intake through diet, improve gut health, and use supplements that support DAO enzyme activity. Avoiding high-histamine foods such as aged cheeses, fermented foods, and certain fish can help minimize symptoms. Probiotics and other gut-supportive supplements can enhance the gut environment, aiding in histamine breakdown. In some cases, DAO supplements can be beneficial, particularly for those with a genetic predisposition. (4)

Genes, Meet Your Friend, the Environment

Exploring the connections between our genes and environmental health highlights the importance of a personalized approach. By understanding the role of the DAO gene in histamine metabolism, we can better address the root causes of conditions like MCAS. At Modern Vital, our aim is to equip you with the knowledge and tools to take control of your health, blending ancient wisdom with modern science. Stay tuned for more insights and practical tips to enhance your well-being.


  1. Valent P, Akin C, Nedoszytko B, Bonadonna P, Hartmann K, Niedoszytko M, Brockow K, Siebenhaar F, Triggiani M, Arock M, Romantowski J, Górska A, Schwartz LB, Metcalfe DD. Diagnosis, Classification and Management of Mast Cell Activation Syndromes (MCAS) in the Era of Personalized Medicine. Int J Mol Sci. 2020 Nov 27;21(23):9030. doi: 10.3390/ijms21239030. PMID: 33261124; PMCID: PMC7731385.
  2. van Odijk J, Weisheit A, Arvidsson M, Miron N, Nwaru B, Ekerljung L. The Use of DAO as a Marker for Histamine Intolerance: Measurements and Determinants in a Large Random Population-Based Survey. Nutrients. 2023 Jun 26;15(13):2887. doi: 10.3390/nu15132887. PMID: 37447214; PMCID: PMC10346277.
  3. Schnedl WJ, Enko D. Histamine Intolerance Originates in the Gut. Nutrients. 2021 Apr 12;13(4):1262. doi: 10.3390/nu13041262. PMID: 33921522; PMCID: PMC8069563.
  4. Izquierdo-Casas J, Comas-Basté O, Latorre-Moratalla ML, Lorente-Gascón M, Duelo A, Soler-Singla L, Vidal-Carou MC. Diamine oxidase (DAO) supplement reduces headache in episodic migraine patients with DAO deficiency: A randomized double-blind trial. Clin Nutr. 2019 Feb;38(1):152-158. doi: 10.1016/j.clnu.2018.01.013. Epub 2018 Feb 15. PMID: 29475774.

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