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Chronic Fatigue

Introduction: What is Mast Cell Activation Syndrome (MCAS)?

Mast Cell Activation Syndrome (MCAS) is a complex immunological condition characterized by the excessive and inappropriate release of many  of the potential one thousand  mast cell mediators, such as histamine, leukotrienes, proteases cytokines, and leukotrienes. This overactivity results in a broad spectrum of symptoms that can fluctuate in both intensity and duration, potentially affecting multiple organ systems and significantly impacting an individual's daily life. Unlike typical allergic reactions, which are predictable and consistent, MCAS symptoms, including anaphylaxis, and various forms of mast cell disorders can be provoked by a diverse range of stimuli, including certain foods, environmental factors, stress, and physical exertion. This variability, coupled with the syndrome's ability to mimic other conditions, often leads to misdiagnosis or years of unexplained symptoms, complicating the path to accurate identification and effective management in both traditional and functional medicine approaches.

Are you “Always Sick?”

Patients with MCAS may describe a history of being "always sick" or present with a variety of chronic, unexplained symptoms that have eluded resolution through traditional medical approaches. The management of MCAS demands a comprehensive strategy that involves identifying and avoiding known triggers, utilizing medications, dietary restrictions and supplementation to stabilize mast cells and mitigate their excessive mediator release, and implementing lifestyle modifications tailored to reduce symptom triggers.

The crux of the challenge in addressing MCAS lies in the mast cells' propensity to become overly reactive, releasing large quantities of mediators spontaneously or in response to stimuli that are typically harmless. This can lead to widespread inflammation and/or allergy type reactions and a range of symptoms that vary greatly in their presentation and severity. For instance, histamine release can lead to dermatological issues like rashes, gastrointestinal distress including abdominal pain and diarrhea, neurological symptoms such as headaches, and even cardiovascular instability. Given the wide-reaching effects of these mediators, MCAS can manifest in ways that are not only challenging to diagnose but also complex to treat.

Developing targeted therapeutic strategies for MCAS requires a deep understanding of the nature of these chemical mediators and their systemic impacts. By focusing on reducing mediator release, blocking receptor activity, or mitigating the effects of these chemicals on the body, healthcare providers can offer relief and improve the quality of life for those affected by MCAS. This multifaceted approach underscores the importance of a personalized treatment plan that addresses the unique triggers and symptoms experienced by each individual.

What are Mast Cells?

Blood Cells that Are Part of Your Immune System

Mast cells, an integral part of the immune system, play a pivotal role in the body's defense mechanisms. 

Found throughout the body, especially in areas exposed to the external environment like the skin, lungs, and digestive system, mast cells act as sentinels, ready to respond at the first sign of invasion or injury. Their primary function is to detect and react to foreign substances, initiating an inflammatory response that aids in the protection and healing of the body.

Histamine Release When in Contact with Allergens 

When mast cells encounter allergens, they release various substances, the most well-known of which is histamine. Histamine's release leads to an increase in blood flow and the permeability of blood vessels, allowing other immune cells to access and address the affected area. This process is crucial for fighting infections but can also lead to the classic symptoms of allergic reactions, including itching, swelling, and redness. Understanding the dual role of mast cells—in both healing and hypersensitivity—highlights their significance in maintaining health and the challenges presented when they malfunction.

Symptoms of MCAS:

The symptoms of MCAS are as diverse as the triggers initiating them, reflecting the widespread presence of mast cells throughout the body. Individuals with MCAS may experience dermatological symptoms such as hives, flushing, and itching, alongside gastrointestinal issues like abdominal pain, nausea, and diarrhea. Respiratory symptoms can include wheezing and shortness of breath, while cardiovascular symptoms may manifest as palpitations or blood pressure and/or pulse fluctuations. Neurologically, patients might report headaches, cognitive difficulties, and mood changes.

Given the systemic nature of MCAS, symptoms can overlap with many other conditions, complicating the diagnostic process. Patients often undergo extensive medical evaluations before receiving a MCAS diagnosis, underscoring the importance of awareness and understanding of this syndrome among healthcare providers. Effective management of MCAS requires a comprehensive approach that addresses the wide range of potential symptoms and their impact on patients' quality of life.


Most Common Symptoms of MCAS Include:

  • "I've been sick for as long as I can remember"
  • "I overreact to bee stings, mosquito bites, penicillin and most medications"
  • "I can't take a full breath"
  • "Whenever I stand up I get lightheaded”
  • Insomnia/sleep disorders starting early in life
  • Tinnitus/ringing in the ears from a young age
  • Vomiting as an infant
  • Abdominal pain as an infant
  • Facial and chest flushing (a red flush when embarrassed or stressed)
  • Dermatographism—a red line appearing on the skin when scratched with a blunt object
  • Frequent infections, cold, viruses, gut viruses as an infant, adolescent or adult
  • Fatigue and malaise
  • Frequent fevers
  • Edema—“water” accumulation in different parts of body
  • Waxing and waning of symptoms
  • Food, drug, and chemical intolerances (especially fragrances). This is a very common symptom which may be exacerbated by phase I and phase II liver detoxification problems as identified by gene testing
  • Sense of being cold all the time
  • Decreased wound healing
  • Hypersensitivity to much in environment, including medications
  • Weight gain or loss
  • Heat intolerance
  • Frequent family history of cancer, especially intestinal or bone marrow (hematologic)
  • Generally feeling inflamed
  • Generalized lymphadenopathy (enlarged lymph nodes)


MCAS Systems by Organ System:

  • Eyes: Red eyes, irritated eyes, dry eyes, burning eyes, difficulty focusing vision, and conjunctivitis (pink eye).
  • Nose: Nasal stuffiness, sinusitis, postnasal drip, hoarseness, laryngitis, nose bleeds (epistaxis), and intranasal sores.
  • Ears: Ringing in ears (tinnitus) and Eustachian tube dysfunction (blocked, popping ears).
  • Throat: Vocal cord dysfunction, throat swelling, sores on tongue/mouth, itchy throat, burning mouth, and difficulty swallowing.
  • Skin: Hives, angioedema (swelling of the skin), skin flushing, itching, skin rashes, dermatographism (when scratched skin causes a red welt), chronic itching, urticarial pigmentosa (legion/hive-like spots on the skin), flushing, bruising easily, reddish or pale complexion, cherry angiomata (skin growths), patchy red rashes, red face in the morning, cuts that won’t heal, fungal skin infections, and lichen planus.
  • Cardiovascular: Fainting, fainting upon standing, increased pulse rate (tachycardia), palpitations, spikes and drops in blood pressure, high pulse or temperature, high triglycerides, lightheadedness, dizzy, hot flashes, and postural orthostatic hypotension syndrome (POTS).
  • Respiratory: Wheezing, asthma, shortness of breath, difficulty breathing deeply, air hunger, dry cough, chronic obstructive pulmonary disease (COPD), and chronic interstitial fibrosis.
  • GI Tract: Left upper abdominal pain, splenomegaly (enlarged spleen), epigastric tenderness, nausea, vomiting, diarrhea and/or constipation, abdominal cramping, bloating, non-cardiac chest pain, malabsorption, GERD/acid reflux, cyclic vomiting syndrome, colonic polyps, and gastric polyps.
  • Liver: High bilirubin, elevated liver enzymes, and high cholesterol.
  • Neurological: Numbness and tingling (especially in the hands and feet), headaches, migraines, tics, tremors, pseudo-seizures, true seizures, waxing and waning brain fog, memory loss, poor concentration, difficulty finding words, and spells of cataplexy (suddenly becoming disconnected from and unresponsive or unreactive to the world around).
  • Musculoskeletal: Muscle pain, fibromyalgia, increased osteopenia, osteoporosis, weakness, and migratory arthritis (joint pain).
  • Coagulation: History of clots, deep vein thrombosis, increased bruising, heavy menstrual bleeding, bleeding nose, and cuts that won’t stop bleeding.
  • Blood disorders: Anemia, increased white blood cell count, platelets, decreased white blood cell counts, decreased neutrophils, decreased lymphocytes, decreased platelets, reductions in CD4 helper lymphocytes, reductions in CD8 positive suppressor lymphocytes, reductions or excesses of IgA, IgG, IgM, IgE, a known condition called MGUS, myelodysplastic syndrome (reduced red cells, white cells, platelets), and increased MCV (mean corpuscular volume).
  • Psychiatry: Anxiety, panic, depression, obsessive compulsive disorder (OCD), decreased attention span, attention deficit/hyperactivity disorder (ADHD), forgetfulness, and insomnia.
  • Genitourinary: Interstitial cystitis, recurrent bladder infections, sterile bladder infections, and frequent urination.
  • Hormones: Decreased libido, painful periods, heavy periods, infertility, and decreased sperm counts.
  • Dental : Deteriorating teeth.
  • Anaphylaxis: Difficulty breathing, itchy hives, flushing or pale skin, feeling warm after exposure, weak and rapid pulse, nausea, vomiting, diarrhea, dizziness and fainting.

What Triggers Mast Cell Activation Syndrome?

Identifying and managing triggers is a cornerstone of MCAS treatment. Triggers can be highly individual, with common ones including certain foods (especially those high in histamine), alcohol, medications (such as NSAIDs and opioids), environmental factors (like pollen and scents), physical stress (heat, cold, or exercise), and emotional stress including a history of early developmental and/or inherited trauma . The variability of triggers and the individual response make managing MCAS particularly challenging, requiring patients to become adept at recognizing and avoiding their specific provocateurs.

Keep a Diary

Patients are often advised to keep a detailed diary of their symptoms and potential triggers, facilitating the identification of patterns and the development of personalized avoidance strategies. Collaboration with healthcare providers to implement dietary changes, modify medications, and adopt stress-reduction techniques plays a critical role in reducing flare-ups and improving overall symptom control.

Mast Cell Activation Syndrome (MCAS) triggers can vary widely among individuals, but some common ones are known to provoke symptoms in many patients. Identifying personal triggers is a crucial step in managing MCAS effectively. Here are 20 common triggers that have been identified:


10 High Histamine Foods that Should be Avoided

  1. Yeast and Alcohol: Products containing yeast and alcoholic beverages can elevate histamine levels.
  2. Dairy: Especially fermented dairy products like kefir, which can be high in histamine.
  3. Gluten: Found in wheat, barley, and rye, gluten can trigger histamine release in sensitive individuals.
  4. Fermented Foods: Such as sauerkraut, kombucha, and miso, are known for their high histamine content.
  5. Cured and Smoked Meats and Fish: These can contain elevated levels of histamine due to the curing process.
  6. Shellfish: Often high in histamine and can trigger reactions.
  7. Citrus Foods: Including lemon, lime, and orange, which can provoke histamine release.
  8. Vinegar: And foods containing vinegar, like pickles and some salad dressings, are high in histamine.
  9. Leftover and Aged Food: Histamine levels in food can increase with age, especially if not frozen immediately.
  10. Berries: Particularly strawberries, blueberries, and raspberries, are known to have high histamine levels.

12 Environmental Triggers

  1. Temperature Extremes: Exposure to very hot or very cold temperatures.
  2. Medications: Certain drugs like NSAIDs, opioids, and antibiotics may trigger symptoms.
  3. Insect Bites and Stings: Venom from bees, wasps, and ants.
  4. Perfumes and Fragrances: Found in personal care products, cleaning supplies, and air fresheners.
  5. Environmental Pollutants: Pollen, mold spores, dust mites, and air pollution.
  6. Sun/UV Exposure: Can prompt mast cell activation in some individuals.
  7. Pressure Changes: Physical pressure or vibration, including wearing tight clothing.
  8. Infections: Viral, bacterial, and fungal infections can initiate mast cell activation.
  9. Laundry Detergents and Fabric Softeners: Chemicals in these products can be triggers.
  10. Latex: Found in medical and household products.
  11. Plasticizers and Phthalates: Chemicals in many plastics.
  12. Alcohol-Based Sanitizers and Hand Washes: The high alcohol content and other chemicals can provoke reactions.

3 Bio-Chemical, Emotional or Physiological Triggers

  1. Physical Stress: Including intense exercise or physical trauma.
  2. Emotional Stress: Psychological stress can provoke symptoms.
  3. Hormonal Changes: Fluctuations during menstrual cycles, pregnancy, or menopause.

Conditions Associated with Mast Cell Activation Syndrome:

Because MCAS is a chronic, multi-system, multi-symptom condition with an inflammatory theme, it’s been associated with a number of conditions and diseases, including:

  • Chronic inflammatory response syndrome
  • Irritable bowel syndrome
  • Gut dysbiosis – the gut is rich in mast cells and home to over 70% of the immune system. Parasites, bacteria, fungi, and parasites can all trigger gut mast cells.
  • Obesity
  • Diabetes
  • Asthma and allergies
  • Autism
  • Autoimmune diseases (such as lupus, rheumatoid arthritis, and Hashimoto’s)
  • Candida overgrowth
  • Celiac disease
  • Parasite infections
  • Skin conditions such as eczema and psoriasis
  • Food intolerances and allergies
  • Gastroesophageal reflux (GERD)
  • Infertility and endometriosis
  • Chemical and medication sensitivities
  • Postural orthostatic hypotension (POTS)
  • CIRS – exposure to mold mycotoxins is a potent stimulator of mast cell activation
  • Migraines
  • Depression
  • Fibromyalgia
  • Fungal infections
  • Tinnitus
  • Multiple Sclerosis
  • Cancer

In general, inflammation accompanies MCAS and most of its coinciding or associated illnesses. If you are struggling to get one of these illnesses under control, there’s a possibility MCAS could be causing further complications. It’s a good idea to check for MCAS if you have any of the above conditions and vice versa.

What's the Difference Between MCAS and Mastocytosis?

Distinguishing between MCAS and mastocytosis is vital for appropriate diagnosis and treatment. While both conditions involve dysregulation of mast cells, their pathophysiology differs significantly. MCAS is characterized by the inappropriate and excessive release of mast cell mediators without an abnormal increase in mast cell numbers. This condition is primarily functional, with mast cells reacting to various triggers in an exaggerated manner.

Mastocytosis, on the other hand, involves the proliferation of mast cells within the body, leading to an increase in their number. This can occur in various tissues and organs, causing symptoms due to both the physical presence of excessive mast cells and their mediator release. Mastocytosis is often identified through specific markers and biopsy, showing the clonal expansion of mast cells, a feature not present in MCAS. Understanding these differences is crucial for tailoring treatment approaches to each condition's unique challenges.

Diagnosis:

A proper diagnosis of MCAS requires the presence of several symptoms from the above list. In addition, other disorders should be ruled out by a specialist in functional medicine.

MCAS is so difficult to diagnose because it may present in so many varied ways that traditional health care providers are not always trained to assess. There is a tremendous range of possible presentations, with local and remote effects which wax and wane over time.

Lab tests can be done to check for mast cell mediators. Tryptase is one of the most common mediators released by mast cells in those with mastocytosis (abnormal numbers of mast cells), but not for those with MCAS (abnormal release of proinflammatory mediators by mast cells, but not an increased number, as in the much rarer mastocytosis). Lab tests can also check for other mediators, such as histamine and prostaglandins; however, most doctors and many labs, particularly those in Canada, will not run the tests that are required to make the diagnosis.

Sometimes patients are able to identify triggers of their MCAS. These may be food or non-food triggers. Pay close attention to what you’ve eaten and have been exposed to when symptoms worsen.

After symptoms have been identified, other conditions have been ruled out, lab tests have been analyzed, and some treatment techniques have proven to relieve symptoms, an official diagnosis of MCAS is made.

Treating Mast Cell Activation Syndrome :

Treating MCAS involves a multi-pronged approach that includes medication, multiple  lifestyle adjustments, and dietary modifications. Medications may include antihistamines to block the effects of histamine, mast cell stabilizers to prevent mediator release, and leukotriene inhibitors to reduce inflammation. Dietary strategies focus on reducing intake of high-histamine foods and identifying individual food triggers that exacerbate symptoms.


Restoring The Natural Health Cycle

In addition to pharmacological and dietary interventions, lifestyle modifications such as stress reduction techniques, gentle exercise, and avoiding known environmental triggers can be beneficial.

The goal of treatment is not only to manage acute symptoms but also to reduce the frequency and severity of MCAS flare-ups, ultimately improving the patient's quality of life. Primary to the management of mast cell activation syndrome is the awareness of how a person best returns their physiology to what has been termed by Dr Robert Naviuax in his groundbreaking papers on mitochondria and the cell danger response, to the natural Health Cycle.

How Does a Functional Medicine Doctor Approach MCAS?

A functional medicine approach to MCAS looks beyond symptom management, seeking to identify and address the underlying causes of mast cell overactivity. This holistic strategy involves a detailed assessment of the patient's medical history, lifestyle, and environmental exposures to uncover potential triggers of MCAS. Functional medicine practitioners may utilize advanced diagnostic testing to assess gut health, nutritional deficiencies, and genetic factors contributing to the condition.

Treatment plans are highly personalized, focusing on dietary interventions, nutritional supplementation, gut health restoration, and lifestyle changes aimed at reducing mast cell triggers. By addressing the root causes of MCAS, functional medicine aims to restore balance and function to the immune system, offering a path to long-term management and symptom relief.

Natural Treatments for Mast Cell Activation Syndrome:

Managing Mast Cell Activation Syndrome (MCAS) often involves a combination of strategies, including natural treatments that can help stabilize mast cells and mitigate symptoms. Here are several natural treatments that may be beneficial for individuals with MCAS, though it's important to consult with a healthcare provider before starting any new treatment to ensure it's appropriate for your specific condition:

  1. Quercetin: A natural flavonoid found in many fruits and vegetables, quercetin is known for its mast cell-stabilizing properties and ability to reduce histamine release.
  1. Vitamin C: This essential vitamin can support the degradation of histamine and has been shown to stabilize mast cells.
  1. Omega-3 Fatty Acids: Found in fish oil and flaxseed oil, omega-3 fatty acids can have anti-inflammatory effects and may help reduce mast cell activation.
  1. Curcumin: The active component of turmeric, curcumin, has anti-inflammatory properties and may help stabilize mast cells.
  1. Magnesium: Magnesium supplementation can be beneficial as it helps reduce histamine release and supports overall immune function.
  1. Bromelain: An enzyme found in pineapples, bromelain can help reduce inflammation and may assist in breaking down histamine.
  1. Stinging Nettle: Often used in herbal medicine, stinging nettle can have antihistamine and anti-inflammatory effects.
  1. Peppermint: Peppermint oil and peppermint tea may help soothe gastrointestinal symptoms related to MCAS due to their anti-inflammatory properties.
  1. Vitamin D: Adequate levels of vitamin D are important for immune regulation, and supplementation may benefit those with MCAS, particularly if levels are low.
  1. DAO Enzyme Supplements: Diamine oxidase (DAO) is an enzyme that helps break down histamine in the digestive tract. Supplementing with DAO can help reduce histamine levels and alleviate food-related symptoms.
  1. Butterbur: This herb has been used to treat headaches and migraines, which can be common in people with MCAS. It's thought to have anti-inflammatory and antihistamine effects.
  1. Probiotics: Certain strains of probiotics may help balance the gut microbiome, which can influence immune function and potentially reduce mast cell activation.
  1. Saline Nasal Irrigation: For individuals with respiratory symptoms, saline nasal irrigation can help clear irritants and allergens that may trigger mast cell activation.
  1. Stress Management Techniques: Practices such as yoga, meditation, and deep breathing exercises can help manage stress, which is a known trigger for MCAS.
  1. Avoiding Trigger Foods: Following a low-histamine diet by avoiding foods known to trigger mast cell activation can help reduce symptoms.

It's crucial to approach the management of MCAS with a comprehensive strategy that includes both medical and natural treatments. Collaborating with a healthcare provider experienced in treating MCAS is essential to develop a personalized treatment plan that addresses your specific needs and symptoms.

Does MCAS Get Progressively Worse?

The progression of MCAS can vary significantly among individuals, making it a condition with unpredictable trajectories. For some people, MCAS symptoms may remain stable over time, while others may experience periods where symptoms worsen or become more frequent. There are also cases where individuals notice an improvement in their symptoms, either through effective management strategies or spontaneously.

Several factors can influence the course of MCAS, including stress, hormonal changes, exposure to new triggers, and the development of other health conditions. Stress, in particular, is known to exacerbate MCAS symptoms due to its ability to stimulate mast cell activation. Similarly, exposure to new allergens or environmental triggers can lead to an increase in symptom severity or the emergence of new symptoms.

Effective management of MCAS is crucial in preventing the worsening of symptoms. This typically involves a combination of avoiding known triggers, using medications to stabilize mast cells and reduce mediator release, and implementing lifestyle changes aimed at minimizing stress and other exacerbating factors. Regular monitoring and adjustments to the treatment plan by healthcare providers can also play a significant role in controlling the condition's progression.

While MCAS can be a chronic condition for many, it does not necessarily mean it will get progressively worse for everyone. With proper management, individuals with MCAS can lead fulfilling lives, experiencing periods of symptom reduction or remission. It's important for those with MCAS to work closely with their healthcare team to develop and maintain an effective management strategy tailored to their specific needs and circumstances.

Does MCAS Ever Go Away?

Mast Cell Activation Syndrome is currently understood to be a chronic condition, and as such, there is no known cure that makes it "go away" entirely for all individuals. However, the severity of symptoms and the frequency of flare-ups can vary greatly from person to person, and with effective management, some individuals may experience significant improvements, to the point where symptoms become minimal or largely manageable.

The course of MCAS is highly individualized, and while some may find their symptoms remain constant, others may experience periods of remission where symptoms are significantly reduced or even absent for a time. The variability in symptom expression and severity is influenced by a wide range of factors, including stress levels, exposure to triggers, underlying health conditions, and effectiveness of treatment strategies.

Management strategies for MCAS typically focus on identifying and avoiding triggers, utilizing medications to reduce or block the release of mast cell mediators, and adopting lifestyle modifications to support overall health and reduce symptom triggers. For many, a combination of these approaches can lead to a marked improvement in quality of life and may result in long periods of symptom stability or remission.

It's important for individuals with MCAS to work closely with healthcare providers experienced in treating this condition to tailor a management plan that addresses their specific needs and symptoms. Through ongoing management and adjustments to treatment strategies, individuals with MCAS can often find ways to control their symptoms effectively, leading to improved outcomes and periods where the impact of MCAS on daily life is minimized.

In summary, while MCAS may not go away entirely, with proper management and care, it is possible for individuals to experience significant improvements and periods of reduced symptom activity, contributing to a better quality of life.

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