Introduction
Adverse reactions to food can be broadly categorized as either food allergies or food intolerances. A food allergy is an IgE antibody-mediated immune reaction that can range from mild itching to life-threatening anaphylaxis. In contrast, a food intolerance is a non-immune reaction, such as the enzyme deficiency seen in lactose intolerance. Histamine intolerance and Mast Cell Activation Disorder (MCAD)—also known as Mast Cell Activation Syndrome (MCAS)—fall into this category. While rarely life-threatening, these conditions can make daily life quite miserable for those affected.
What is Histamine?
Most people recognize the term “antihistamine” in the context of seasonal allergies, but histamine itself performs many helpful functions, such as stimulating stomach acid production. In the immune system, histamine acts as a defense mechanism. When the body perceives a threat, mast cells release histamine, causing inflammation to signal the immune system to respond. However, in histamine intolerance or MCAD, histamine either isn’t broken down properly or is released inappropriately when no actual allergen is present.
Understanding the Histamine “Bucket”
Histamine intolerance is often compared to an overflowing “bucket.” Normally, histamine is rapidly degraded by two enzymes: diamine oxidase (DAO), which works primarily in the digestive tract, and histamine-N-methyltransferase (HNMT), which deactivates histamine at the receptor level throughout various body tissues. If these enzymes are dysfunctional, histamine accumulates. This differs from Mastocytosis (too many mast cells) or MCAD (mast cells that “spill” their contents inappropriately), though all these disorders result in high histamine levels.
The Four Types of Histamine Receptors
Histamine binds to four specific receptors, each causing different systemic reactions:
- H1 Receptors: Involved in allergic rhinitis (sneezing), asthma symptoms, and enlarging blood vessels.
- H2 Receptors: Stimulate stomach acid release and modulate the immune response.
- H3 Receptors: Affect neurotransmitter release in the central nervous system, including serotonin.
- H4 Receptors: Found in bone marrow, white blood cells, and the digestive tract.
Common Dietary Triggers
Some foods are naturally high in histidine, which converts to histamine during digestion. High-histamine foods include aged cheeses, yogurt, fermented vegetables like kimchi or sauerkraut, smoked fish, and alcohol. Additionally, some “histamine liberators” like chocolate and tomatoes can trigger mast cells to release their own stored histamine, adding further to the body’s total load.
Symptoms and Diagnosis
Symptoms are incredibly diverse, often leading to misdiagnosis as Irritable Bowel Syndrome (IBS) or simple food poisoning. Gastrointestinal distress can occur within minutes or several hours after eating. Non-GI symptoms include skin hives, facial flushing, heart palpitations, extreme fatigue, and “brain fog.” Because these symptoms appear unrelated, it takes an average of 14 years for a patient to be properly diagnosed with MCAD, usually through an immunologist or allergist.
More Info?
Learn about me and the dietary support I provide for Mast Cell Activation Syndrome (MCAS), Ehlers-Danlos Syndrome – hypermobility subtype (hEDS), Postural Orthostatic Tachycardia Syndrome (POTS), and histamine intolerance. View my Therapeutic Diet Services page.
To your good health!
Joy
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References
- Baily N. Histamine Intolerance. Igennus Healthcare Nutrition. [https://www.slideshare.net/igennus/managing-histamine-intolerance-80982438]
- Molderings GJ, Brettner S, Homann J, et al. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. Journal of Hematology & Oncology. 2011 Mar 22;4:10. [https://doi.org/10.1186/1756-8722-4-10]
- Hamilton MJ, et al. Mast cell activation syndrome: A newly recognized disorder with systemic clinical manifestations. Journal of Allergy and Clinical Immunology. 2011;128(1):147-152. [https://doi.org/10.1016/j.jaci.2011.04.037]
- Jernigan D. Histamine Intolerance Syndrome. Hansa Center for Optimal Health. [https://www.marioninstitute.org/histamine-intolerance-syndrome/]
© 2025 BetterByDesign Nutrition Ltd.
Joy is a Registered Dietitian Nutritionist and owner of BetterByDesign Nutrition Ltd. She has a postgraduate degree in Human Nutrition, is a published mental health nutrition researcher, and has been supporting clients’ needs since 2008. Joy is licensed in BC, Alberta, and Ontario, and her areas of expertise range from routine health, chronic disease management, and digestive health to therapeutic diets. Joy is passionate about helping people feel better and believes that Nutrition is BetterByDesign©.