Mast Cell Activation Syndrome (MCAS) is often discussed as if it appears suddenly and without explanation. In reality, mast cell dysfunction almost always develops in response to deeper, ongoing stressors in the body.
For individuals dealing with chronic Lyme disease and complex chronic illness, MCAS is rarely the primary problem. Instead, it is usually a downstream effect of immune overload, pathogens, environmental exposure, and nervous system dysregulation.
Understanding the root causes of MCAS is essential for making meaningful progress, especially when symptoms feel unpredictable or treatment approaches are difficult to tolerate.
MCAS Is a Pattern, Not a Standalone Disease
MCAS occurs when mast cells become overly sensitive and release inflammatory mediators inappropriately. While genetic factors can influence susceptibility, most cases are acquired, meaning that something is pushing the immune system into a chronically reactive state.
In chronic illness, this process typically unfolds over time rather than appearing all at once.
1. Chronic Infections
One of the most common contributors to MCAS is persistent infection. Long-standing infections such as Lyme disease, Bartonella, Babesia, EBV, etc.. place continuous demand on the immune system, preventing inflammatory signals from fully shutting down.
Over time, this ongoing immune activation can condition mast cells to remain hypersensitive, leading to exaggerated responses to otherwise mild triggers. This may explain why symptoms fluctuate and why tolerance to treatments can decrease as illness becomes more chronic.
2. Mold Exposure and Mycotoxins
Environmental exposure to mold and mycotoxins is a powerful driver of mast cell activation. Mycotoxins are highly inflammatory compounds that can directly stimulate mast cells and amplify immune responses. In our practice we see mold exposure as on of the leading causes the tip the body’s bucket over and fuel MCAS.
In susceptible individuals, mold exposure may contribute to escalating sensitivities, difficulty tolerating detoxification, and worsening reactions despite appropriate treatment strategies. When mold exposure is ongoing or unrecognized, mast cell activation may persist regardless of other interventions. Treatments that once worked for you and helped maintain your health, your body can now see as dangerous and begin flare up from them. We this especially with therapies that included saunas and cold plunges, as mast cells can be very reactive to temperature change.
3. Gut Dysfunction and Microbiome Imbalance
The gastrointestinal tract contains a large concentration of immune cells, including mast cells. When gut function is compromised, mast cells may become more reactive.
Factors such as dysbiosis, increased intestinal permeability, small intestine bacterial over growth (SIBO), food sensitivities, and chronic inflammation can all contribute to mast cell activation. This helps explain why digestive symptoms are common in individuals with MCAS and why food reactions often play a central role.
Gut dysfunction frequently overlaps with other root causes, creating a cycle that perpetuates immune instability. Many individuals that suffer from MCAS often are only able to eat a handful of different types of foods without their body experience a negative reaction. It is so important to stabilize mast cells and repair the gut so that food can once again be thought of as nourishing the body instead of feared.
Implementing a low histamine diet can significantly reduce daily mast cell activation and help stabilize symptoms. This typically means avoiding aged, fermented, cured, or leftover foods, as histamine increases the longer food is stored—even in the refrigerator. Emphasizing freshly prepared meals and freezing leftovers if they are not eaten within 24 hours can help lower overall histamine exposure. In some cases, patients may also benefit from support before meals, such as taking a DAO (diamine oxidase) enzyme to help break down histamine in the gut, or using cromolyn sodium as prescribed to stabilize mast cells in the gastrointestinal tract and reduce mediator release during digestion. These strategies can meaningfully reduce food-triggered reactions and improve tolerance while broader immune and nervous system regulation is addressed.
4. Impaired Detoxification and Toxic Load
When the body’s ability to process and eliminate toxins is overwhelmed, mast cells may respond as part of a defensive response. Environmental toxins, heavy metals, and inflammatory byproducts can all contribute to mast cell dysregulation.
In this state, attempts to support detoxification may provoke symptoms rather than relieve them. Individuals who once felt better after taking glutathione to help expel toxins from their body, often can feel wired and anxious, or experience swelling and hives. Focusing on stabilizing mast cells first is KEY in responding to treatments that target detoxification or pathogens. Sensitivity to chemicals, fragrances, and supplements is often a sign that mast cells are reacting to an excessive toxic burden.
5. Nervous System Dysregulation
Mast cells are closely connected to the nervous system, particularly the autonomic nervous system. Chronic stress, trauma, and prolonged illness can keep the body in a constant state of alert.
When the nervous system remains in a threat response, mast cells may stay primed for activation. This relationship explains why emotional stress can trigger physical symptoms and why calming the nervous system may help reduce the frequency or intensity of mast cell reactions.
Looking into programs or therapies that help regulate the nervous system is essential in taking back control of your body. EFT taping, yoga, humming can all help. There are also programs such as the GUPTA program, Primal Trust, and DNRS support the body in getting out of survival mode and feeling safe again in their own skin.
6. Repeated Immune Overactivation
Repeated inflammatory episodes can further sensitize mast cells over time. Strong immune reactions may condition the body to respond aggressively even when the original trigger has diminished.
This can result in heightened reactivity to treatments, supplements, and everyday stimuli. As immune flexibility decreases, symptom patterns may become more unpredictable and difficult to manage. The book Body Keeps The Score by Bessel Van Der Kolk is a great resource to help understand what happens when your body has taken to many hits creating disfunction in the immune system.
7. Genetic Susceptibility and Individual Thresholds
The last of the causes of Mast Cell Activation Syndrome are genetic factors. Genetic factors alone rarely cause MCAS, but they can influence how resilient the immune system is under stress. Some individuals may tolerate significant immune or environmental challenges before developing symptoms, while others may reach a threshold more quickly. There is a gene known as the HLA-DR gene that doesn’t allow the body to expel mold mycotoxins as effectively as it should. About 30% of the population has this gene, which can create a predisposition to mold illness and later MCAS.
Genetic variability helps explain why MCAS presents differently from person to person and why personalized approaches are often necessary.
Why Identifying Root Causes of Mast Cell Activation Syndrome Matters
Addressing MCAS effectively requires more than symptom management. Without reducing the underlying drivers of mast cell activation, relief is often temporary.
Identifying and addressing root causes can help restore immune balance, improve treatment tolerance, and create more stable progress over time. A HUGE part of this, is making sure your environment (home, working space, etc…) is conducive to allowing your body to heal.
A Broader Perspective on Healing
MCAS is rarely the beginning of illness; it is usually a signal that the body has been under sustained stress. By understanding what drives mast cell activation, individuals and practitioners can better support long-term healing rather than focusing solely on short-term symptom control. At The Lyme Specialist, we are Certified Mold Practitioners and Certified MCAS specialists that can help navigate what is running the show, and how to help move your health forward.
