CIRS, Histamine Intolerance, and Mast Cell Activation Syndrome

Many individuals dealing with chronic health conditions often face multiple sensitivities that complicate the healing process. Chronic Inflammatory Response Syndrome (CIRS) is a complex condition that can bring a cascade of health challenges, often triggering multiple sensitivities and immune system imbalances. Two common issues that arise in CIRS patients are histamine intolerance and Mast Cell Activation Syndrome (MCAS). These conditions can add another layer of difficulty, complicating the treatment process and amplifying symptoms such as headaches, skin reactions, digestive distress, and anxiety.

 

Histamine intolerance and MCAS can sometimes be overlooked in CIRS patients, but addressing these sensitivities is essential for effective treatment. Managing histamine levels can involve a combination of dietary strategies, lifestyle modifications, and temporary “bandaid” solutions to reduce symptom severity. Keeping histamine levels under control allows patients to experience fewer flare-ups and a smoother healing journey.

 

We’ll explore why CIRS often triggers histamine-related issues, and how to navigate treatment when histamine intolerance or MCAS is present. Let’s take a closer look into dietary approaches, supplement support, and practical strategies to help alleviate these sensitivities, so you can progress through CIRS treatment with greater ease and reduced symptom burden.

 

What Is CIRS?

 

 

Chronic Inflammatory Response Syndrome (CIRS) is a multifaceted health condition that affects various systems throughout the body, causing a wide range of symptoms. It is driven by heightened inflammation due to an overreactive immune system. Diagnosing CIRS requires extensive lab testing and a thorough evaluation of the patient’s health history, making it a condition that is often difficult to pinpoint.

 

Due to its diverse symptom presentation, CIRS is frequently misdiagnosed or not treated correctly. Unlike other immune-related disorders that are typically identified through conventional autoimmune testing, CIRS doesn’t show up in these standard tests. This creates a need for a more specialized diagnostic approach to properly recognize and address the condition. Accurate diagnosis is crucial to providing targeted treatment that addresses the root cause and supports the patient’s long-term recovery.

 

 

What causes the heightened immune response and systemic inflammation seen in CIRS? The key culprits are biotoxins—harmful substances that set off and worsen CIRS symptoms. These toxins can originate from multiple sources, including:

 

• Water-Damaged Buildings: Approximately 80% of CIRS cases are linked to exposure in water-damaged environments. These areas are often filled with mold mycotoxins, bacteria, and other irritants that trigger inflammation in vulnerable individuals. Even remnants from dead mold can provoke widespread inflammation, impacting both physical and cognitive health.

 

• Insect Bites: Certain insect bites, like those from ticks and spiders, can result in chronic conditions such as Lyme disease. Pathogens such as Borrelia burgdorferi and Babesia microti, along with venom from recluse spider bites, can lead to prolonged health complications and trigger CIRS in susceptible people.

 

• Seafood Consumption: Eating tropical reef fish contaminated with ciguatera toxin, often due to harmful algal blooms, is another biotoxin source. Larger reef fish accumulate these toxins by consuming smaller, contaminated fish, posing a risk to those who consume them.

 

• Contaminated Water Exposure: Inhaling or coming into contact with water contaminated by toxic algae blooms—such as cyanobacteria and *Pfiesteria*—can initiate the inflammatory response typical of CIRS.

 

• Additional Biotoxin Sources: Other potential triggers include certain vaccines, viral infections, volatile organic compounds (VOCs), endotoxins, and actinomycetes, which can all play a role in the onset and progression of CIRS.

 

 

Biotoxins are microscopic particles capable of penetrating cell membranes, making them challenging to detect through conventional blood tests. These harmful substances typically enter the body through inhalation, but they can also be introduced by ingesting contaminated food, through insect bites, or by coming into contact with polluted water sources.

 

Not everyone exposed to biotoxins like mold will develop CIRS. Genetic factors and life circumstances significantly influence the risk of developing biotoxin-related illnesses. Factors such as severe illness, surgeries, high fevers, pregnancy, intense biotoxin exposure, or traumatic events can trigger a cytokine storm, activating CIRS in those who are genetically predisposed, especially individuals with specific HLA-DR genes. This means that CIRS can emerge unexpectedly at any stage of life. It’s also important to note that a lack of symptoms does not ensure immunity, making genetic testing a valuable tool for identifying potential risks.

 

While many individuals can naturally eliminate biotoxins, those genetically prone to CIRS have immune systems that struggle to recognize and clear these toxins. As a result, biotoxins persist in the body, leading to chronic inflammation and a host of long-term health complications.

 

For a more detailed understanding of CIRS, click here.

 

Pro-Tip: If you think you’re suffering from CIRS, start with our White Glove Service for comprehensive care.

 

What Is the Shoemaker Protocol?

 

 

The Shoemaker Protocol, created by Dr. Ritchie Shoemaker, is a detailed, step-by-step treatment plan specifically designed to address Chronic Inflammatory Response Syndrome (CIRS) and other biotoxin-related conditions. It is the only peer-reviewed, clinically validated approach for treating biotoxin illnesses, including mold exposure. This structured protocol systematically addresses the complex impact of biotoxins by targeting the underlying inflammatory pathways that drive symptoms. Each stage is carefully sequenced to tackle various downstream effects of biotoxin exposure, ensuring an efficient and comprehensive treatment process.

 

The protocol begins with eliminating ongoing exposure to biotoxins, whether through mold remediation, avoiding contaminated environments, or implementing other environmental controls. Once exposure is minimized, the next focus is on removing biotoxins from the body using specific binders such as Cholestyramine (CSM) or Welchol, which help capture and eliminate these toxins.

 

For those dealing with histamine intolerance or MCAS, the protocol may need adjustments. These individuals often struggle with increased inflammation and sensitivities, making it essential to adopt a low-histamine diet and incorporate temporary supports to manage histamine levels. Stabilizing histamine is crucial to ensure better tolerance of the Shoemaker Protocol, including medications, binders, and supplements.

 

As the treatment progresses, subsequent steps work to rebalance the immune response, correct hormonal imbalances, and address inflammatory markers. This includes restoring normal cytokine levels, addressing hormone deficiencies, and resolving other downstream effects of biotoxin exposure. Following each stage methodically aims to restore immune and endocrine balance, ultimately leading to significant symptom reduction and CIRS remission.

 

The Relationship Between CIRS and Histamines

One of the notable connections between CIRS and histamine issues lies in the innate immune system’s response. Histamines, which play a crucial role in defending the body from harmful substances, increase as the immune system is activated. In the case of CIRS, this activation is often accompanied by elevated C4A, a marker for immune response. As C4A levels rise, so do histamines, contributing to inflammation and the characteristic symptoms of histamine intolerance.

 

Histamine intolerance and MCAS are both linked to the body’s inability to effectively manage toxins. Beyond individual susceptibility or triggers such as CIRS, the core issue is an overburdened system. The body’s detoxification pathways are overwhelmed, leading to an accumulation of toxins and pathogens that disrupt normal immune function. Mast cells, which are designed to clear harmful substances, including allergens, are forced to work overtime. This overactivation leads to a heightened release of histamine, exacerbating inflammation and resulting in symptoms such as hives, headaches, digestive issues, and more.

 

When the body remains in a toxic state for too long, the immune system, including the function of mast cells, can become dismantled. Rather than clearing toxins and protecting the body, mast cells are overstimulated and contribute to the immune system’s dysfunction. This toxic burden can trigger excessive histamine release, worsening symptoms for those with CIRS and increasing the likelihood of MCAS. Managing this toxic overload is key to restoring balance to the immune system and reducing histamine-related symptoms.

 

Understanding Mast Cells and Their Roles

 

Mast cells are an essential part of the immune system, originating from stem cells in the bone marrow. These versatile cells are found in most tissues throughout the body, particularly in areas that are regularly exposed to the outside environment, such as the gastrointestinal (GI) tract, lungs, nose, and skin. Not only do they reside in these external-facing tissues, but they also interact with neurons, further linking the immune system with other critical bodily functions. Mast cells play a crucial role in detecting and responding to foreign substances, serving as one of the body’s first lines of defense.

 

When mast cells detect a threat, they become activated and undergo a process known as degranulation. This involves the release of granules containing more than 200 different chemicals called “mediators.” These mediators manage a wide variety of immune responses, and one of the most well-known is histamine, which is stored in large quantities within mast cell granules. While histamine can also be produced by cells in the nervous and digestive systems, mast cells are the primary source of histamine in the body.

 

Mast cells are involved in a broad range of functions beyond just immune defense. They contribute to the body’s defense against pathogens, the development of immune tolerance, the formation of new blood vessels, and inflammatory processes. Additionally, mast cells help maintain the integrity of the blood-brain barrier and play a role in wound healing. These functions highlight the importance of mast cells and their mediators for normal, healthy body function.

 

However, when mast cells become overactive, as they do in individuals with MCAS, problems can arise. In these cases, mast cells release excessive amounts of mediators, including histamine, leading to an overactive inflammatory response. This can cause a range of symptoms, from allergic-like reactions to more systemic issues, such as histamine intolerance. The excess histamine and other mediators exacerbate inflammation, creating a cycle that can be difficult to manage without addressing the underlying triggers.

 

MCAS vs. Histamine Intolerance vs. Allergies

 

 

MCAS and histamine intolerance are two conditions that involve abnormal responses to histamine, but they have different underlying mechanisms and triggers. Both can lead to frustrating, often debilitating symptoms, but distinguishing between the two is essential for effective management.

 

MCAS occurs when mast cells become overly reactive and release excessive amounts of histamine and other inflammatory substances. Mast cells play a critical role in the immune system, helping to defend the body against infections and allergens. However, in MCAS, these cells are hyper-sensitive and can be triggered by a variety of factors, such as stress, infections, environmental toxins, and certain foods. This overactivation results in a wide range of symptoms, including skin rashes, itching, flushing, digestive issues, headaches, and even cardiovascular or respiratory problems. MCAS is often associated with other chronic conditions such as CIRS, Lyme disease, and autoimmune disorders.

 

Histamine intolerance, on the other hand, comes from a buildup of histamine that exceeds the standard amount required for normal functioning. Under normal conditions, certain enzymes break down excess histamine. More specifically, the enzyme diamine oxidase (DAO) is responsible for degrading excess histamine. The substances produced from histamine breakdown are sent to the kidneys and excreted in the urine. Typically, this ensures histamine levels don’t exceed the level where symptoms start to appear.

 

When DAO levels are too low or overwhelmed by high histamine intake, histamine builds up in the body, leading to symptoms that mirror an allergic response—headaches, flushing, nasal congestion, gastrointestinal issues, and skin reactions. One way to tell the difference between histamine intolerance and allergies is immediate vs. delayed reactions. If you react immediately to a specific allergen (e.g., peanuts), then it’s easy to recognize a reaction to a specific allergy.

 

However, if you experience symptoms outside a trigger, it’s possible you have a build-up of excess histamine over time, leading to histamine intolerance. Along with this, histamine intolerance tends to produce more comprehensive symptoms that affect a wide range of systems in the body.

 

The primary difference between MCAS and histamine intolerance lies in their root cause. MCAS is an immune system disorder where the mast cells themselves are malfunctioning, while histamine intolerance stems from the body’s inability to adequately break down dietary histamine.

 

In practice, the two can overlap, as individuals with MCAS can also struggle with histamine metabolism, but the treatment approaches may differ. Managing MCAS often involves stabilizing mast cells with medications or supplements, while histamine intolerance is typically addressed through dietary changes and supplements to support DAO activity.

 

What Are MCAS Symptoms?

 

MCAS manifests in a wide range of symptoms due to the release of numerous chemical mediators, including histamine, from mast cells. Since these cells are present in many tissues throughout the body, MCAS affects multiple systems, making it a complex, multi-system disorder. Here is a comprehensive breakdown of the symptoms associated with MCAS:

 

1. Skin-Related Symptoms:

• Itching
• Swelling
• Flushing
• Hives
• Lesions
• Burning or Tingling Sensations
• Easy Bruising
• Slow Wound Healing

 

2. Throat and Gastrointestinal Symptoms:

• Itchy, Burning, or Tight Throat
• Acid Reflux
• Bloating
• Abdominal Cramps
• Nausea or Vomiting
• Diarrhea or Constipation

 

3. Respiratory Symptoms:

• Wheezing
• Shortness of Breath
• Persistent Cough
• Asthma-like Issues
• Sinusitis
• Rhinitis
• Excessive Mucous Production

 

4. Cardiovascular Symptoms:

• Low Blood Pressure
• Rapid Heartbeat
• Palpitations
• Chest Pain
• Faintness or Fainting
• Lightheadedness or Dizziness

 

5. Neurological and Cognitive Symptoms:

• Brain Fog
• Anxiety
• Headaches
• Difficulty Focusing or Remembering
• Trouble Finding Words
• Sleep Disturbances
• Vertigo or Dizziness
• Neuropathic Pain
• Numbness
• Tinnitus (Ringing in the Ears)

 

6. Systemic and General Symptoms:

• Excessive Sweating
• Fever-like Sensations
• Body Temperature Irregularities
• Depression
• Muscle, Bone, or Joint Pain
• Arthritis or Hyperflexibility
• Weakness and Fatigue

 

7. Eye Symptoms:

• Itching
• Redness
• Watery or Dry Eyes
• Eye Pain

 

8. Bladder and Urinary Symptoms:

• Bladder Pain
• Frequent or Urgent Urination

 

9. Reproductive Symptoms:

• Reproductive or Menstrual Cramps
• Painful Periods
• Endometriosis
• Hormonal Imbalances
• Erectile Dysfunction

 

The diverse nature of MCAS symptoms stems from the widespread distribution of mast cells throughout various organs and tissues. When these cells become overactive, they release a wide array of mediators, leading to the extensive, multi-systemic symptoms that are characteristic of MCAS.

 

What Are Histamine Intolerance Symptoms?

Since histamine intolerance primarily arises from an imbalance in the body’s ability to process histamine, it can lead to a variety of symptoms. While it can affect multiple systems, the scope of symptoms is typically narrower compared to MCAS. Here is an overview of the common symptoms associated with histamine intolerance:

 

1. Skin Symptoms:

• Itching
• Hives
• Flushing

 

2. Gastrointestinal Symptoms:

• Bloating
• Abdominal Discomfort or Pain
• Diarrhea
• Nausea
• Vomiting

 

3. Respiratory Symptoms:

• Nasal Congestion
• Runny Nose
• Wheezing
• Asthma-like Reactions

 

4. Cardiovascular Symptoms:

• Headaches
• Dizziness
• Low Blood Pressure
• Rapid Heartbeat

 

5. Neurological Symptoms:

• Headaches
• Migraines

 

• 6. Other Symptoms:
  Fatigue

 

What Triggers MCAS and Histamine Intolerance?

 

 

While MCAS often has a genetic component, it is influenced by a variety of triggers. These triggers can range from environmental factors, such as mold and chemical exposure, to physical stress, infections, and hormonal imbalances. Certain foods, medications, and even physical exertion can also activate mast cells in individuals with MCAS, leading to a range of symptoms. The genetic predisposition to MCAS, combined with the presence of numerous external and internal triggers, makes managing this condition particularly challenging, as the cause of flare-ups may vary from person to person.

 

One of the most common causes of histamine intolerance is a deficiency of DAO. When DAO levels are insufficient, histamine accumulates, triggering symptoms. In some cases, MCAS itself can lead to histamine intolerance, as excessive histamine release overwhelms the body’s ability to process it. Other potential causes include mutations in the histamine N-methyltransferase (HNMT) gene, which is responsible for breaking down histamine in the liver, and overproduction of histamine in response to infections or inflammatory conditions.

 

Poor liver function can also contribute to histamine intolerance. In cases of sluggish bile flow or poor drainage from the liver and bile ducts, the body struggles to eliminate histamine effectively, exacerbating symptoms. Additionally, poor methylation in the liver, often linked to genetic variations or chronic illness, can further reduce the body’s ability to process histamine. CIRS and activation of the innate immune system can also play a role in histamine intolerance by increasing histamine production and reducing the body’s ability to detoxify it.

 

Supporting Histamine Intolerance and MCAS in CIRS

Individuals with CIRS who also suffer from histamine intolerance and/or MCAS can face a complex challenge in managing these conditions. It’s essential to work closely with your trusted CIRS practitioner to develop a personalized treatment plan. Because each person’s body responds differently, finding the right combination of prescription medications, over-the-counter options, and natural supplements is crucial. This process is highly bio-individual, meaning what works for one person may not work for another. It often involves trial and error to determine the best products to stabilize mast cells, reduce histamine levels, and support overall healing.

 

You can also find our recommendations for some of the natural histamine supports for CIRS here.

 

A low-histamine, meat-based diet is often recommended as a powerful tool for individuals dealing with CIRS, MCAS, and histamine intolerance. For many, this dietary approach can be as effective, if not more so, than relying solely on supplements or medications. Eliminating foods that trigger histamine release, such as aged meats, fermented products, and many inflammatory vegetables allows individuals to reduce their histamine load and give the body a chance to heal. In many cases, this dietary intervention can greatly improve symptoms and overall quality of life.

 

For many individuals, treating CIRS can resolve histamine intolerance and lead to significant improvements in MCAS. Once the underlying inflammation and immune dysregulation are addressed, histamine-related symptoms often diminish. However, for others, additional toxins such as Lyme disease or heavy metals may need to be addressed to fully resolve histamine intolerance. These conditions are often downstream effects of a deeper issue that requires root-cause healing. Addressing these core imbalances is key to long-term recovery and symptom relief.

 

For the remainder of this content including our thoughts and recommendations on CIRS histamine supports, please join our CIRS Group.

 

Closing Thoughts on CIRS, Histamine Intolerance, and MCAS

Living with histamine intolerance and MCAS can indeed add another layer of complexity for individuals already managing CIRS. However, it’s important to remember that there are many supportive measures available to help reduce symptoms and improve your quality of life. Working with a knowledgeable practitioner allows you to develop a personalized plan that includes the right combination of dietary changes, medications, and natural supplements to stabilize histamine levels and calm overactive mast cells.

 

While managing these conditions may require extra planning and mindfulness around your diet and lifestyle, this is not a permanent situation. These adjustments are simply part of your journey toward root-cause healing. As you address the underlying triggers and toxins that are driving CIRS, many of the symptoms related to histamine intolerance and MCAS can begin to resolve.

 

Take heart in knowing that each step you take is bringing you closer to lasting relief and a healthier, more balanced life. With patience, persistence, and the right support, healing is not only possible but within reach. Stay encouraged, and remember—you are not alone on this journey.

 

 

Pro-Tip: Are you looking for more in-depth practitioner resources and a like-minded community to support you through your CIRS journey? Join our exclusive CIRS Support Group for the latest research, step-by-step protocol tools, and support to successfully achieve root-cause healing.

 

Work With Our Trusted CIRS Practitioners

The Nutrition with Judy practice is honored to be a trusted CIRS practitioner support serving clients from around the globe. We’re passionate about helping our clients achieve root-cause healing in order to lead the best quality of life possible that’s nearly symptom-free. Our team is dedicated to finding the answers our patients need. We welcome you to explore our free resources and are always available to support you through personalized protocols. If you’re interested in working one-on-one with our CIRS nutritional therapy team to support you through your journey, our CIRS Support Package delivers the support and accountability for achieving root-cause healing.