Mast Cell Activation Syndrome: Symptoms and Solutions
Mast Cell Activation Syndrome (MCAS) is a complex and chronic immune disorder. It affects multiple systems in the body including the skin, gastrointestinal tract, heart, respiratory, and neurologic systems. Unfortunately, most people with MCAS suffer for months, or even years, without a diagnosis due to the lack of awareness within the medical community.
Mast cells are immune cells that have the central role of protecting the body. When these cells are overactive and release too many mediators, this can be harmful to the body. MCAS may play a role in cancer, stroke, Lyme disease, and many other serious conditions.
The first step to improve symptoms of MCAS is to identify and address a person’s individual triggers. This may include certain foods, mold, chemicals, and other toxins. A low histamine and/or low FODMAP diet may help to improve symptoms of MCAS. In this article, I will also discuss targeted supplements to support the immune system.
What are Mast Cells?
Mast cells were discovered in 1878 by Nobel Prize winner and immunologist Paul Ehrlich. Ehrlich discovered these small immune cells which reside in the tissues and are mediators of allergic, inflammatory, and autoimmune conditions.
Mast cells are involved in both the innate and adaptive immune systems. They are the body’s first line of defense against pathogens and form barriers against foreign substances entering the body.
Mast cells are found in most tissues of the body. They are abundant in mucosal surfaces that are in close contact with the external environment, such as our skin, respiratory system, and gastrointestinal system (1).
When activated, mast cells produce many chemical mediators. These include histamine, leukotrienes, heparin, cytokines, phospholipases, tryptase, chymase, chemokines, growth factors, and cholinesterase. These mediators are released into surrounding tissue. This leads to swelling and inflammation, which are necessary for healing to occur.
While generally associated with allergic response, mast cells are also involved in the regulation of many other functions in the body. These include immune tolerance, innate immunity, wound healing, and angiogenesis (formation of new blood vessels).
MCAD and MCAS
Mast Cell Activation Disorder or Disease (MCAD) is an umbrella term for the realm of diseases of the mast cell. There are three types of MCAD: primary, secondary and idiopathic (2). Primary MCAD includes mastocytosis, a rare disease characterized by an overgrowth of mast cells with inappropriate mast cell activation.
There are two principle types of mastocytosis, cutaneous (limited to the skin) and systemic (throughout the body). More common mast cell disorders include allergies, urticaria, angioedema, and anaphylaxis.
Secondary MCAD is the reactive form of MCAD. This occurs in allergies, chronic inflammatory diseases, neoplastic disorders, physical urticarias, and chronic autoimmune urticaria (3). With secondary MCAD, mast cells are produced normally and can be increased in response to an underlying inflammatory process.
Mast Cells and MCAS
Idiopathic MCAS is a type of MCAD that is a more nebulous activation of the mast cells. It is not caused by an abnormally large amount of mast cells, but rather a normal amount of mast cells that are overactive and malfunctioning.
When your body is exposed to a perceived threat, the overactive mast cells secrete massive amounts of chemical mediators from the cytoplasm of the cells. This cellular process is called degranulation.
MCAS occurs when degranulation occurs too much and too often. Chronic release of chemical mediators triggers a negative immune response rather than a protective response. This can lead to chronic, multisystem inflammation. MCAS most commonly affects women.
Common Symptoms of MCAS
MCAS can affect every system in the body and cause a large array of possible symptoms (4). Common symptoms of MCAS divided by body system include:
- Constitutional: fatigue, malaise, chronic fatigue syndrome; flushing, feels cold much of the time, chemical and/or physical environmental sensitivities, sweats, increased or decreased appetite
- Cardiovascular: pulse and blood pressure variability (low blood pressure and rapid pulse are common), palpitations, tachycardia, vascular permeability (inflammation and swelling), lightheadedness
- Respiratory: wheezing, shortness of breath, cough, sinusitis, rhinitis, increased-mucus production, asthma-like symptoms, runny nose
- Neurological: headaches, irritability, anxiety, depression, brain fog, difficulty concentrating, vertigo, tingling, tremors, tics
- Psychological: anger, anxiety, depression, ADHD, PTSD, cognitive dysfunction, insomnia and other sleep issues
- Gastrointestinal: reflux, nausea, diarrhea, constipation, alternating diarrhea and constipation, vomiting, abdominal cramping, bloating
- Dermatological: rashes, itching, swelling, flushing, hives
- Musculoskeletal: joint pain, fibromyalgia-type pain, arthritis, joint hypermobility
- Skeletal: osteopenia and osteoporosis, scoliosis
- Genitourinary: pain and irritation in the urinary tract and/or genitals, urinary frequency or hesitancy
There are no definitive tests for MCAS. Mast cells release over 200 mediators, and there are less than ten of these mediators that are specific to mast cells and can be measured clinically.
Serum tryptase, the most abundant protein in mast cells, can be helpful in diagnosing mastocytosis (4). With mastocytosis, tryptase levels may be double or more the upper limit of normal. Mastocytosis is confirmed with a bone marrow biopsy. For MCAS, tryptase is usually normal, or slightly abnormal and bone marrow biopsies are usually unrevealing.
In addition to tryptase, serum chromogranin A and plasma prostaglandin D2, histamine, leukotriene, and heparin can be helpful in diagnosing MCAS (5). In the urine, the metabolites of prostaglandin D2 and histamine and a molecule called leukotriene E4 can be measured. It is important that most of these be chilled for reliability exemplifying the importance of working with a knowledgeable practitioner.
In addition to increased levels of mediators, proposed diagnostic criteria includes: 1) episodic multisystem symptoms consistent with mast cell mediator release; 2) clinical improvement with H1 and H2-receptor antagonists, anti-leukotriene medications, or mast cell stabilizing agents; and 3) no evidence of a primary of secondary MCAD (3).
How Does MCAS Differ from Histamine Intolerance?
Histamine intolerance and MCAS are related conditions. Histamine is an amine that is produced by your cells and found in foods. It is an inflammatory molecule that helps regulate immunity. As part of the immune response, histamine is produced by basophils and by mast cells found in connective tissue.
Most people with MCAS have an exaggerated sensitivity to histamines, but not everyone who is histamine intolerant has MCAS. Instead, there is a spectrum from histamine intolerance to MCAS with symptoms ranging from mild to severe.
An individual with histamine intolerance has an exaggerated reaction to high histamine foods or foods that produce histamine. The causes of this exaggerated reaction could be insufficient DAO enzyme production (needed for proper histamine metabolism) or elevated histamine levels.
With histamine intolerance, a person will notice improvement with a low histamine diet and supportive supplements. A person with MCAS may still be very sensitive even with diet, supplement, and lifestyle strategies. Additionally, MCAS is a potentially more debilitating condition than histamine intolerance affecting multiple organ systems. For more information on histamine intolerance, check out this article.
Triggers of MCAS
People with MCAS are more sensitive to toxins and environmental changes. Antigens and toxins overwhelm the mast cells and exceed the ability of mast cells to respond.
There are a number of antigens or toxins that can trigger MCAS. These include mold, chemicals, parasites, bacterial infections, allergens, viruses, heavy metals, and toxins. Stress (mental, physical, and emotional), heat or cold, hormonal changes, and excessive exercise may also trigger an overreaction of mast cells.
Conditions Linked to MCAS
Mast cell activation is linked to certain cancers, cardiovascular diseases, connective tissue disorders, inflammation, allergies, asthma, irritable bowel syndrome, skin conditions, and autoimmune diseases (5). Mast cells and inflammation of the brain are linked to mental health conditions, including depression and anxiety.
Let’s look at how mast cells play a role in certain conditions:
An inflammatory response to mold exposure can be a driver of MCAS. If you have MCAS, it is important to check for mold exposure and remove yourself from any water damaged buildings.
Mold toxicity occurs when mycotoxins produced by mold lead to a chronic inflammatory immune response. This can be very damaging to the body. To test for mold toxicity, you can do a Mycotoxin Test. This urine test screens for seven different mycotoxins from four species of mold.
Lyme disease is an infectious disease caused by four main species of Borrelia bacteria. It is transmitted by the bite of an infected tick. Lyme disease, as with other infections, can cause mast cells to react and secrete proinflammatory cytokines (6).
There are a number of symptoms associated with Lyme disease, many of which are also common with MCAS. Lyme disease can be very difficult to accurately diagnose. To test for Lyme disease, the Igenex Lyme Test is a sensitive and reliable antibody screening that also screens for the DNA of Borrelia.
Lyme disease can be very challenging to overcome. However, there are effective natural strategies that you can find here.
MTHFR Gene Mutations
Methylation is one of the most essential metabolic functions in the body. It is dependent upon a variety of enzymes that transfer methyl groups onto proteins, amino acids, DNA, and enzymes in every cell and tissue. It helps to regulate healing, cellular energy, genetic expression of DNA, liver detoxification, immunity, and neurology. This article explains the role of methylation in human health.
Methylation one of the most important pathways through which the body breaks down histamine. The most common genetic variant affecting methylation is the methylenetetrahydrofolate reductase (MTHFR) gene.
If methylation is not working well, there are not enough methyl groups to bind to a receptor site on histamine. Histamine is not broken down, and high levels of histamine can accumulate in the body. This causes histamine overload and results in symptoms associated with histamine intolerance and MCAS.
Mast cells are found in connective tissues throughout the body. Researchers have found that dysregulation of mast cells may play a role in Ehlers-Danlos Syndrome (EHS) (7).
EHS is a group of complex and multisystem connective tissue disorders. They are caused by varying genetic defects primarily in the structure, production, and/or processing of collagen. There are 13 subtypes of EHS, each with a specific genetic basis and protein involvement.
EHS mostly affects the joints and skin. An unusually large range of joint movement (hypermobility) occurs in most forms of EHS. Loose joints are unstable and prone to dislocation and chronic pain. Soft, velvety skin that is highly elastic, fragile, and bruises easily is also common. Bone, gastrointestinal, eye, and heart issues are also common with EHS.
Postural Tachycardia Syndrome (POTS) is associated with MCAS (8). POTS is a condition that affects the autonomic nervous system and alters blood flow throughout the body. A person with POTS has an increased heart rate and dizziness or lightheadedness when standing.
When a person also experiences flushing, MCAS should be considered. For more information on POTS and strategies to improve this condition, check out this article.
Neuroinflammatory Conditions and Mast Cells
Mast cells are in the central nervous system where they contribute to the normal behavioral development and functioning (9). They have also been linked to numerous neuroinflammatory conditions of the central nervous system.
These include multiple sclerosis (MS), traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, neuropathic pain, migraines, depression, autism, fibromyalgia, and stroke.
There is growing research on the relationship between mast cells and cancer (10). Researchers have found a significant increase in the prevalence for melanoma and cancers of the breast, cervix, ovaries, lungs, and thyroid in people with MCAS (11). Mast cells can be directly activated by cancer cells.
Mast cells appear to have a dual role in cancer. They can infiltrate tumors and function to promote or restrict tumor growth and invasiveness. By releasing chemokines and initiating an immune response, mast cells may lead to tumor eradication. However, mast cells may release other mediators that support tumor malignancy. Regulating mast cell activation, recruitment, and type of released mediators at the tumor site can be useful for managing and controlling tumor growth (12).
Sensitivity to electromagnetic fields (EMFs) can play a role in activating mast cells. There are a broad range of symptoms associated with EMF sensitivities. These include cognitive issues, insomnia, fatigue, dizziness, joint pain, palpitations, and ringing in the ears.
It is important to reduce the amount of exposure to non-native EMF and to increase exposure to natural forms of EMF available by being outside grounded on the Earth and getting quality sun exposure. For more information on the dangers of EMFs along with ways to protect yourself from exposure, see this article.
Natural Strategies to Improve MCAS
MCAS is a challenging condition to deal and each individual suffering with this will need their own specific health plan. There are several things that are common and effective for the vast majority of people dealing with MCAS. While these aren’t all FDA approved to prevent, mitigate, treat or cure MCAS, many have found these strategies to be extremely helpful.
Some individuals will need to avoid all higher histamine foods while others can tolerate some of them. Experimentation will be key to try to understand what your body tolerates and what it cannot and the supplements that seem to offer the most support.
1. Identify and Avoid Triggers
The first step to improving MCAS is to identify and avoid a person’s specific triggers. As you can see from the list above, there are a variety of things that may be triggering MCAS. It can take time to identify and address these issues. However, as a person’s symptoms improve, tolerance for these triggers may also improve.
2. Use Targeted Supplementation
Vitamin C is a powerful antioxidant that is critical for supporting the immune system. It reduces histamine-mediated inflammation and plays an important role in the synthesis of collagen.
Other natural antihistamines include stinging nettle, butterbur, bromelain, probiotics, and astragalus. Allergy Defense has many of these along with N-Acetyl Cysteine. This combination of bioflavonoids, micronutrients, proteolytic enzymes, and herbs is a powerful supplement for addressing immune hypersensitivity.
Mast cell stabilizers prevent degranulation and stabilize the cell. This prevents the release of histamines. One of the most powerful mast cell stabilizers is quercetin.
Quercetin is a natural antihistamine. It is a powerful antioxidant and the “king of flavonoids.” Quer-C Powder contains quercetin along with vitamin C. This powerful blend works synergistically to improve the inflammatory response and down regulate mast cell activation (14).
Vitamin B6 is a key cofactor that enables DAO to degrade histamine. Without adequate DAO, histamine levels can increase, leading to symptoms of histamine intolerance or MCAS. B6 Power is a bioactive form of vitamin B6 (P-5-P) that is more readily used by the body than other forms of B6.
Diamine oxidase (DAO) is the main enzyme responsible for the degradation of histamine in the digestive tract. In individuals that have a DAO deficiency, supplementing with DAO at meals can be very helpful.
Hista Protect™ is a patented enzyme formula containing DAO. This supplement can help reduce unwanted histamine reactions.
Hista Response contains clinically validated ingredients to support microbiome wellness and overall immune health. LactoSpore® (Bacillus coagulans) is a unique strain of shelf stable lactic acid producing bacteria with a naturally protective spore coating. This strain helps to balance the immune system. Hista Response also contains hyperimmunized egg powder which provides immunoglobulins and immune cofactors to support the body’s natural defenses and help regulate the immune system.
Another good probiotic option for people with immune hypersensitivity is MegaSporeBiotic™. This broad-spectrum spore forming probiotic that has been shown to recondition the gut and may be beneficial for very sensitive individuals who struggle with food sensitivities, poor oxalate metabolism, and histamine intolerance.
3. Treat Underlying Infections
Addressing underlying infections such as small intestinal bacterial overgrowth (SIBO) may help improve symptoms of MCAS. Some gut microbes produce high amounts of histamines as a byproduct of their metabolism.
The difficulty is that It can be hard to address these infections until a person’s MCAS symptoms have improved. People with MCAS are often very sensitive to supplementation, and antimicrobials may be too difficult on their system. Starting with a probiotic and immune support may help improve symptoms so that a person can tolerate antimicrobials.
Large concentrations of mast cells are in the mucous. MegaIgG2000 is a dairy-free immunoglobulin concentrate that supports a healthy mucosal immune system. This formula helps to decrease immune activation and strengthen gut barrier function. Once a person is more stable, infections can be addressed with an antimicrobial protocol.
Nutrition Plan for Improving MCAS
Individuals with MCAS can be very sensitive to additives, preservatives, and colors in processed foods. Consuming an anti-inflammatory diet of whole, unprocessed foods is critical for anyone with MCAS. These foods include grass-fed, pastured, organic meats, wild-caught fish, organic fruits and vegetables, and healthy fats.
MCAS can make a person highly reactive to histamines and other compounds in foods. It can take time to identify a person’s unique food triggers. However, implementing a low-histamine and/or low-FODMAP diet is a good starting point to help improve the symptoms of MCAS.
Low Histamine Diet
An individual with histamine intolerance has an exaggerated reaction to high histamine foods. The causes of the exaggerated reaction to high histamine foods could be insufficient DAO enzyme production or elevated histamine levels. To improve symptoms of MCAS a low-histamine diet may be very beneficial.
High histamine foods to avoid:
- Fermented dairy, such as cheese, kefir, yogurt, sour cream, buttermilk, and cream cheese
- Fermented alcohol: wine, champagne, beer
- Aged cheeses
- Fermented vegetables and fermented soy products (kimchi, sauerkraut, and pickled vegetables, soy sauce)
- Vinegars and foods with vinegars such as pickles, mayonnaise, and olives
- Cured meats such as bacon, salami, peperoni, lunch meats and hot dogs
- Dried fruits: apricots, prunes, dates, figs, and raisins
- Most citrus fruits, berries, stone fruits
- Vegetables: avocados, eggplant, spinach, tomatoes
- Smoked fish, mackerel, mahi mahi, tuna, anchovies, sardines
- Nuts: walnuts, cashews, and peanuts
Foods that release histamines should also be avoided. These include alcohol, cow’s milk, nuts, chocolate, bananas, papaya, pineapple, shellfish, strawberries, tomatoes, wheat germ, artificial preservatives and colors. Alcohol, black tea, energy drinks, green tea, and mate tea act as DAO blockers and should be eliminated on a low-histamine diet.
For more information about histamine intolerance and how to know if you could be suffering, read this article.
Low FODMAPs Diet
FODMAPs are short-chain carbohydrates that are poorly absorbed in the small intestine. They pass along the gut to the large intestine and are fermented by bacteria. This fermentation results in many digestive symptoms like gas, pain, and bloating. A diet high in FODMAPs can contribute to functional gut disorders like irritable bowel syndrome (IBS).
FODMAPs is an acronym for Fermentable Oligo, Di- and Monosaccharides and Polyols. These fermentable sugar-based carbohydrates include fructose, glucose, galactans, polyols, and lactose. FODMAPs can be found in a range of different foods including many healthy foods. The foods that should be avoided are:
- Oligo-saccharides (fructans): found in vegetables (artichokes, beets, asparagus, onions, garlic, mushrooms), wheat, rye
- Galacto-oligosaccharides (galactans): found in legumes and pulses (chickpeas, kidney beans, lentils, butter beans, black-eyed peas, soybeans)
- Disaccharides (lactose): milk, yogurt, and cheeses like cottage cheese, cream cheese, and ricotta
- Mono-saccharides (excess fructose) found in fruits like apples, apricots, cherries, figs, mangoes, peaches, pears, plums, and watermelon, sweeteners like agave nectar, corn syrup, and honey
- Polyols (sorbitol and mannitol) found in fruits (apricots, avocados, blackberries, peaches, cherries), vegetables (cauliflower, mushrooms), sweeteners (sorbitol, xylitol, mannitol)
How to Implement an Elimination Diet
To implement an elimination diet, avoid high histamine and/or high FODMAPs foods for around 4-6 weeks. Once you remove these foods, your body can begin to heal, and you may notice improvement in symptoms.
After the elimination period, slowly reintroduce foods that were eliminated. While reintroducing foods, it is important to record all foods consumed with any positive or negative symptoms. You should modify the nutrition plan based on the results of reintroduction and expand the diet to include foods with as much variety and nutrient density as tolerated.
Final Thoughts on MCAS
Mast cells are an important part of your immune system and necessary to heal from injuries. Mast cell activation syndrome occurs when mast cells are overactive and release too many chemical mediators. This can cause serious problems in the body.
There are natural strategies to help people manage the symptoms of MCAS. The first step is to identify and remove any potential triggers of your symptoms. If there are any toxins, infections, pathogens, or other environmental triggers, these must be addressed.
Implementing a low histamine and/or low FODMAP diet may relieve symptoms. Additionally, supplementing with flavonoids and other nutrients that help to stabilize mast cells may be very beneficial for helping improve the immune response.
Follow the tips, strategies and supplements I recommend for supporting MCAS and see if you notice improvement. If you are doing these thing and still struggling with this condition, then I would recommend working with a functional health coach who can help you identify the root causes and customize a specific plan to get well.