MCAS and Histamine: Why Mast Cell Symptoms Are Not Always Histamine-Driven
- Muriel Wallace-Scott
- Feb 23
- 4 min read
Updated: Oct 31
Mast Cell Activation Syndrome (MCAS) is a complex condition that arises when mast cells release their chemical mediators inappropriately. These immune cells play a vital role in defence and tissue repair, but when they become overactive, they can trigger a wide range of symptoms across multiple body systems.
While histamine is one of the most recognised mast cell mediators, it is far from the only one. In fact, mast cells can release over 200 different substances, including enzymes, cytokines, prostaglandins, and leukotrienes. This diverse mediator profile helps explain why some individuals with MCAS do not experience full relief from antihistamines or low-histamine diets.
In other words, not all mast cell symptoms are driven by histamine alone.
→ Not sure where to start? MCAS is a complex condition so we get it. Our practitioners can help make sense of your symptoms and support you accordingly. Feel free to book a discovery call to discuss how we can help you.
Understanding the Role of Histamine
Histamine is a naturally occurring compound involved in immune defence, stomach acid regulation, and neurological signalling. It plays an important part in allergic reactions by widening blood vessels and increasing their permeability.
However, problems can arise when histamine levels rise excessively or the body struggles to break it down efficiently. This can lead to histamine intolerance, a condition marked by symptoms such as:
Headaches or migraines
Flushing or hives
Nasal congestion
Gastrointestinal discomfort
Rapid heart rate or dizziness
These symptoms can closely resemble those of MCAS, which can make diagnosis and treatment confusing. The key difference is that histamine intolerance is primarily about histamine metabolism, whereas MCAS involves the release of multiple inflammatory mediators, of which histamine is only one.
Beyond Histamine: The Many Mediators of Mast Cells
Mast cells are remarkable for their ability to release a wide range of mediators that affect different organs and tissues. Some of the key non-histamine mediators include:
Tryptase: An enzyme involved in tissue remodelling and chronic inflammation.
Prostaglandins: Lipid-based compounds that promote inflammation and pain.
Leukotrienes: Substances that can cause bronchoconstriction and mucus production.
Cytokines and Chemokines: Immune signalling molecules that recruit and activate other immune cells.
Because mast cells can release such a variety of mediators, MCAS can manifest with symptoms affecting multiple systems — from the gut and skin to the cardiovascular and neurological systems. This variability explains why two individuals with MCAS may have very different symptom profiles and responses to treatment.
MCAS vs Histamine Intolerance: Understanding the Difference
Although MCAS and histamine intolerance share some overlapping features, they are distinct in their mechanisms:
Histamine Intolerance: Primarily involves excessive histamine or reduced capacity to break it down, often due to low diamine oxidase (DAO) activity.
Mast Cell Activation Syndrome (MCAS): Involves inappropriate mast cell activation and the release of multiple mediators, including but not limited to histamine.
This means that a person with MCAS may not experience complete symptom relief from a low-histamine diet or antihistamine therapy, because other mediators such as prostaglandins, leukotrienes, or cytokines may still be active.
Why Treating MCAS Requires a Broader Approach
When histamine-focused treatments only bring partial improvement, it can be a sign that other mast cell mediators are contributing to symptoms. In clinical practice, this means treatment must extend beyond antihistamines to include mast cell stabilisation, anti-inflammatory support, and nervous system regulation.
A personalised plan may include:
Identifying and addressing environmental or dietary triggers
Supporting detoxification and antioxidant pathways
Using targeted nutrients and supplements that help stabilise mast cells
Managing stress and sleep to reduce nervous system overactivation
By addressing the full spectrum of mast cell activity, rather than histamine alone, it is possible to achieve deeper and more sustainable symptom relief.
Supporting MCAS and Histamine Intolerance at The Autoimmune Clinic
At The Autoimmune Clinic, we understand the complexity of mast cell activation and the frustration that comes when symptoms persist despite following a low-histamine diet.
Under the guidance of Muriel Wallace-Scott, our team provides an individualised, functional medicine approach to help identify the underlying drivers of mast cell activation and calm the system as a whole.
Our process includes:
Comprehensive Evaluation: Assessing your health history, symptom patterns, and laboratory results to identify triggers and mediators involved.
Personalised Treatment Plans: Combining dietary strategies, supplement support, and lifestyle interventions aimed at reducing mast cell reactivity.
Symptom Relief and Long-Term Regulation: Addressing both immediate discomfort and long-term immune balance for sustainable improvement.
Ongoing Support: Continuous review and adaptation of your plan as your body begins to stabilise.
Our goal is to help you understand your condition, restore resilience, and achieve a better quality of life—without unnecessary restrictions.
In Summary
While histamine plays a major role in both MCAS and histamine intolerance, it is only part of the story. Mast cell activation involves a wide network of inflammatory mediators that can affect every system in the body. Recognising this distinction is crucial for effective, long-term management.
If you suspect MCAS or histamine intolerance, we invite you to book a discovery call to explore how our team can help you identify triggers, reduce inflammation, and restore balance.
