Mast cells are crucial components of our immune system, acting as sentinels that release various mediators like histamine, serotonin, and tryptase when triggered by an allergen, pathogen, or toxin. Their primary function is to alert the body and rally an immune response. However, in cases of Mast Cell Activation Syndrome (MCAS) these cells become hyperactive, leading to chronic or excessive release of histamine and other inflammatory mediators. In the case of histamine intolerance, the body has difficulty breaking down histamine due to deficiencies in enzymes, resulting in elevated levels of histamine. This can result in both physical and neuropsychiatric symptoms, particularly in individuals with PANS/PANDAS or chronic illnesses like Lyme disease and mold toxicity.
Histamine and Its Impact
Histamine is one of the primary mediators released during mast cell activation. While histamine’s primary role is to help regulate immune responses, it can cause inflammation and dysfunction when levels become dysregulated. MCAS can manifest in numerous ways, such as skin rashes, gastrointestinal distress, cardiovascular issues, and neuropsychiatric symptoms like anxiety, depression, and OCD. In children with PANS/PANDAS, histamine can worsen neuropsychiatric symptoms, leading to mood swings, aggression, and cognitive issues.
Think of histamine as a fire alarm: under normal circumstances, it sounds to warn the body of an incoming threat. But in MCAS, the alarm system malfunctions, and the warning system goes off repeatedly, even in the absence of a true threat. This constant state of alert fuels chronic inflammation and can be particularly exacerbated by triggers such as mold exposure, chronic infections like Lyme disease or Epstein-Barr Virus, or even stress.
MCAS vs. Histamine Intolerance
Though both MCAS and histamine intolerance involve high levels of histamine in the body, they are distinct conditions. In MCAS, the primary issue lies with the mast cells themselves—they become overly sensitive and react to a wide range of triggers such as mold, infections, or environmental toxins, releasing histamine and other mediators. This condition is not just about histamine; it involves the release of additional inflammatory substances like serotonin and prostaglandins, which further exacerbate symptoms.
On the other hand, histamine intolerance occurs when the body has difficulty breaking down histamine due to deficiencies in enzymes like diamine oxidase (DAO). This condition is specifically related to the accumulation of histamine, often triggered by foods high in histamine (such as aged cheeses, fermented foods, or alcohol). While MCAS can be triggered by a variety of environmental and internal factors, histamine intolerance is more likely to flare up after eating certain foods.
Both conditions can overlap, particularly in individuals with PANS/PANDAS, where the body’s already fragile balance is tipped even further by histamine overload. However, the treatment approach for each condition can vary significantly depending on the root cause. For example, addressing mast cell stabilization may be key in MCAS, while enzyme supplementation or dietary changes are often more effective for managing histamine intolerance.
Root Causes and Triggers
In many cases, mast cell activation and histamine overload are secondary to other underlying issues such as:
- Mold and Mycotoxin Exposure: Mold exposure is a leading trigger for MCAS, particularly in sensitive individuals. Mold releases mycotoxins that exacerbate histamine release and disrupt the immune system.
- Chronic Infections: Bacterial infections like Lyme, Bartonella, or viral reactivations (e.g., Epstein-Barr virus) are common culprits that drive mast cell activation.
- Environmental Toxins: Everyday environmental toxins, such as volatile organic compounds (VOCs) from cleaning products or natural gas, can fuel chronic inflammation and histamine issues.
Dr. Neil Nathan, MD, a leading expert in treating complex medical conditions, estimates that 70-80% of his patients with mold toxicity also suffer from MCAS. He explains that the inflammatory response driven by mold exposure makes the mast cells hypersensitive, leading to chronic, often debilitating symptoms.
Impact of Genetics
Genetic mutations, such as SLC22A4 or DAO gene mutations, impair the body’s ability to clear histamine effectively, leading to symptoms even with normal histamine levels . These genetic susceptibilities make it even harder for some individuals to process histamine, resulting in symptoms that can range from minor discomfort to severe reactions.
Neuroinflammation and MCAS
Mast cell activation can drive neuroinflammation, which is a critical factor in PANS/PANDAS. Neuroinflammation occurs when activated mast cells in the brain’s blood vessels release histamine, which can cross the blood-brain barrier, intensifying neurological symptoms like anxiety, depression, and cognitive decline. This inflammation in the brain, particularly in sensitive children with conditions like PANS/PANDAS, can severely impact their behavior and mental health.
Resveratrol, a natural compound, has shown promise in attenuating neuroinflammation by modulating the glial cell response to cytokines, which can reduce brain inflammation and improve cognitive function in cases of chronic neuroinflammation.
1. Identify Triggers and Reduce Exposure:
- Mold Exposure: Address mold in the home environment by using air purifiers with HEPA filters and ensuring proper ventilation. Mold often hides behind walls or in air ducts, so professional inspection may be necessary.
- Dietary Adjustments: Implement a low-histamine diet, avoiding aged, fermented, and processed foods, which can liberate histamine. Keep a food diary to track symptoms and identify food triggers.
2. Support Detoxification:
- Encourage detoxification pathways using natural binders like activated charcoal and chlorella to help remove toxins and mycotoxins from the body.
- Liver support is crucial for processing histamine, so consider incorporating herbs like milk thistle and nutrients such as N-acetylcysteine (NAC) for antioxidant support.
3. Use Antihistamines and Natural Supplements:
- Natural antihistamines like quercetin and curcumin help stabilize mast cells and reduce histamine release. DAO supplements can be particularly beneficial for those with DAO gene mutations, as they increase the breakdown of histamine in the gut.
- For neuroinflammatory symptoms, resveratrol is a potent compound shown to reduce brain inflammation.
4. Address Underlying Conditions:
- Treat chronic infections like Lyme and Bartonella with a combination of antimicrobials, both herbal (e.g., Japanese Knotweed) and conventional, to reduce the infectious load that may be driving histamine production.
- For individuals with severe sensitivities, limbic system retraining and vagal nerve stimulation can help reset the overactive fight-or-flight response that often accompanies MCAS. Dr. Neil Nathan has found that his MCAS patients, especially those with mold exposure, require limbic system retraining and vagal nerve stimulation.
By addressing the root causes of mast cell activation, such as infections, mold toxicity, and genetic predispositions, along with reducing histamine triggers, significant improvement can be achieved in managing MCAS and histamine intolerance.
See the Herbal Guide for information on herbal antihistamines and Mast Cell Stabilizers.