Alex Iturregui, functional medicine health coach



MAST CELL ACTIVATION SYNDROME



MAST CELLS



Mast cells are immune/defense cells created in the bone marrow. They are released into the bloodstream, and then they go into the peripheral tissues, almost all tissues throughout the body that are in close contact with the environment, such as your skin, mouth, eyes, ears, airways, gastrointestinal tract, as well as in nerves, ligaments, tendons, bones cardiovascular and reproductive systems, and the brain. Anything that is vascularized is where they are finishing up their maturation process. The environment controls their maturation. Mast cells have several jobs: assisting with wound healing, maintaining the blood barrier, and, most importantly, being the first responder for the body. Whenever foreign invaders (fungi, bacteria, viruses), allergens, or environmental toxins enter the body, mast cells alert the rest of the immune system to defend you, releasing a vast array of mediators all at once.


WHAT IS MAST CELL ACTIVATION SYNDROME (MCAS)?



The inappropriate, chronic, multisystem release of mediators from mast cells is called Mast Cell Activation Syndrome, or MCAS. First recognized only a decade ago, Mast Cell Activation Syndrome is a complex disorder that is prevalent in the chronically ill population. You have an average amount of mast cells, but they are overreacting. When mast cells become overly reactive, they may react to real threats like viruses, bacteria, or environmental toxins, but they don't stop responding when the threat has cleared. They can even start reacting to safe foods, supplements, medications, or weather changes.


Mast cells have special sacs that contain granules, which contain hundreds of chemical messengers or mediators. According to Lawrence Afrin, MD, a leader expert on Mast Cell Activation Syndrome, there may be more than 1000 mediators.

When mast cells react, they release these mediators; this process is called degranulation. One of the most well-known mediators is histamine. Common histamine reactions include swelling, itching, redness, and hives.

Other mediators include tryptase, heparin, prostaglandins, leukotrienes, and cytokines. Different mediators can cause a unique physiological reaction to surrounding tissue. Tryptase is a proteolytic enzyme and can break down nerve endings.


Mast cells can explosively release or gradually leak their mediators. No cellular element of the immune system reacts faster than mast cells. Lymphocytes take hours to activate, and neutrophils require minutes, but mast cells can respond to a trigger in a fraction of a second.


Mast cell activation syndrome is a complex health issue involving several different systems in your body, which can cause a constellation of symptoms.


MCAS causes chronic inflammation in multiple organs/tissues/systems, with or without allergic-type problems and sometimes even abnormal growth and development in various tissues, and there can be acute flares of symptoms from time to time.  Although its variability in clinical presentation can make it difficult to initially recognize MCAS as the underlying/unifying root of the typical patient's many ills, doctors specialized in MCAS increasingly recognize that MCAS is a common problem. Even though MCAS is not presently curable, there are many treatments known to help control the disease.


Increasing awareness in patients and their physicians is critical and can only help those who have long been mysteriously suffering from the disease.


WHAT CAUSES MCAS?


Many people may be affected by mast cell activation syndrome due to underlying causes, including mold exposure, toxin exposure, other environmental exposures like pesticides, herbicides, formaldehyde, and volatile organic compounds, bacterial, viral, or/and fungal infections, nervous system dysregulation, and genetic predisposition.


In a new study by researchers at The University of Texas Health Science Center at San Antonio, also known as UT Health San Antonio, Dr Claudia Miller; Raymond F. Palmer, PhD, Nicholas A. Ashford, PhD, JD, of MIT; and Tania T. Dempsey, MD, and Lawrence B. Afrin, MD, of the AIM Center in Purchase, New York, they found that mast cells can be sensitized by a single acute exposure to xenobiotics such as pesticides or solvents, or by repeated lower-level exposures, such as breathing volatile organic compounds (VOCs) associated with remodeling or new construction. After that, even low levels of those and other unrelated substances can cause the mast cells to release the mediators, leading to inflammation and illness.


MCAS TRIGGERS


Some of the most common mast cells triggers:


   • Toxic Mold  

   • Toxic Chemicals (such as Fragrances, Herbicides, Pesticides, etc.)

   • Chemicals in Personal, Beauty, and Cleaning Products

   • Airborne Smells from Chemicals or Smoke

   • Infections. Lyme Disease, Co-Infections, EBV (Epstein Barr), Mold Colonization, Parasites.

   • Heavy Metal Toxicity. Aluminum, Mercury, including mercury from dental work, Cadmium, Bismuth, and Arsenic are known to be mast cell destabilizers

   • Certain Foods. Such as those high in Histamine, Lectins, Sugar, Preservatives, and Food Coloring.

   • Alcohol

   • High Stress and Trauma

   • Medications that Liberate Histamine or Block DAO

   • Excipients in Medications and Supplements

   • Anesthetics

   • Insect Bites. Ants, Spiders, Ticks, Fleas, Mosquitos, Bed Bugs, etc.

   • Temperature and Barometric Pressure Changes

   • Vibration

   • Hormone Imbalances

   • Certain Genetics

   • Lack of Sleep


COMMON SYMPTOMS OF MCAS


Symptoms commonly seen across the population of MCAS patients include:


   • CARDIOVASCULAR: Fast or Irregular Heartbeats (Palpitations, Tachycardia), High and Low Blood Pressure, Lightheadedness, Dizziness, Chest Pain, Fainting or Feeling Fainth, Hypercoagulation

   • DIGESTIVE: Nausea, Vomiting, Heartburn, Reflux, Diarrhea, Constipation, Abdominal Cramps, IBS, Food Sensitivities, Mouth Burning, Throat Swelling, Tongue Swelling

   • EYES/EARS: Dry, Itching, or Burning Eyes, Conjunctivitis, Watery Eyes, Visual Disturbance, Ringing in the Ears, Hypersensitivity to Light or Sound

   • GENITOURINARY: Interstitial Cystitis, Irritable Bladder, Urinary Tract Infections, Ovarian Cysts, Painful Bladder, Endometriosis, PMS, Male and Female Infertility, Vaginitis, Dyspareunia (Pain on Intercourse)

   • GROWTH and DEVELOPMENT: Delayed Puberty, Poor Healing, Connective Tissue Disorders

   • MUSCULOSKELETAL: Aches, Muscle and Bone Pain, Osteoporosis, Arthritis that moves around, Hyperflexible Joints (it may or may not be Ehlers-Danlos Syndrome)

   • NEUROLOGICAL: Headaches, Migraines, Brain Fog, Poor Concentration/Memory, Anxiety/Panic, Tingling, Numbness, Insomnia, Dizziness, Tinnitus (ringing in the ears), Depression, Tremor

   • NODES: Enlarged Lymph Nodes

   • ORAL/NASAL: Sores, Burning Mouth, Pain, Itching, Sinusitis, Sneezing, Runny Nose, Difficulty Swallowing, Dental Deterioration Despite Good Dental Hygiene

   • RESPIRATORY: Nasal Congestion, Shortness of Breath, Asthma, Throat Swelling, Cough, Wheezing

   • SKIN: Rosacea, Psoriasis, Eczema, Rashes, Hair Thinning/Loss, Flushing, Itching, Hives, Edema, Swelling, Dermatographic Urticaria (skin writing), Temperature Dysregulation, Brittleness and Ridging of Nails,

   • SYSTEMIC: Overall Fatigue, Sensitivities to Foods, Medications, Environment, Toxic Chemicals, EMFs, Unusually Vigorous Insect Bite Reactions


CONDITIONS THAT MAY BE RELATED TO MCAS


   • Asthma

   • Autism Spectrum Disorders

   • Certain Cancers

   • Crohn’s Disease

   • Chronic Fatigue

   • Eczema

   • Ehlers-Danlos Syndrome (EDS)

   • Fibromyalgia

   • Graves Disease

   • Guillain- Barré Syndrome

   • Hashimoto’s Thyroiditis

   • IBS (Irritable Bowel Syndrome)

   • Interstitial Cystitis

   • Lupus

   • Multiple Chemical Sensitivity/TILT (Toxicant Induced Loss of Tolerance)

   • Multiple Sclerosis

   • Postural Orthostatic Tachycardia Syndrome (POTS)

   • Psoriasis

   • Rheumatoid Arthritis

   • Rosacea

   • Sjogren’s

   • Type 2 Diabetes


DIAGNOSING MCAS


First, I encourage you to work with a doctor specializing in MCAS. There are few specialists. You can search for them online and see if there are any in your area at the International Society for Environmentally Acquired Illness (ISEAI), The Institute for Functional Medicine (IFM), and the American Academy of Environmental Medicine (AAEM). Also, you can contact me if you need help; I'm happy to help!


Emily Rowe, MD, AP, is my brilliant doctor; she and her husband, Christopher Estes, MD, are specialists in MCAS and other chronic complex health conditions in Miami Beach. You can reach them at their clinic, Miami Beach Comprehensive Wellness Center.


Diagnosis of MCAS can be challenging. Although there is no global consensus yet on diagnostic criteria, most specialists agree that identifying chronic symptoms across multiple organ systems consistent with mast cell activation is essential to the diagnosis. It is also necessary to rule out other diagnoses that better account for the observed symptoms and findings.

It is essential to consider whether there is improvement after removing triggers and supporting the mast cells for the diagnosis.


Some doctors look for elevated mediators in blood and urine that are relatively specific to the mast cell. Measurement of some of these mediators is particularly challenging and requires specialized handling of tissues, including short half-lives and rapid breakdown on exposure to heat. Also, you’ll need to get testing on multiple occasions since the symptoms of MCAS wax and wane. Testing markers only seem to capture about 10 percent of cases.


There is still controversy about testing for high levels of a mast cell mediator called Tryptase. Some researchers say that tryptase should consistently be elevated in MCAS. Others say that tryptase is rarely elevated and it usually stays at levels within the normal range, even when symptoms are flaring.


That said, if your doctor is in the line of testing, here are some of the most common tests they may ask:  

   • Blood Histamine

   • N-Methylhistamine 24-hour urine

   • Blood Prostaglandin D2

   • Blood Chromogranin A

   • Blood Heparin


     

MOST CURRENT STRATEGIES FOR MANAGING MCAS


Managing MCAS is the best you can do at this time. Science says there is no cure for MCAS, but trust me when I tell you that when you find your triggers and root causes and implement the best strategies, you'll begin to feel better, regain health, and find joy again. Don't give up!


Treatment aims to reduce the occurrence and severity of symptoms to improve the patient's quality of life, using a combination of medicinal and natural mast cell stabilizers, different techniques for calming down the nervous and limbic systems, lifestyle changes, and addressing increased gut lining permeabilization, methylation, and detox pathways.


Once you are diagnosed or suspect that you have Mast Cell Activation Syndrome, you can start to feel a lot better by doing the following:


   • IDENTIFY AND ADDRESS YOUR ROOT CAUSES AND TRIGGERS


The initial treatment focus should be identifying and then avoiding the substances that inappropriately trigger the activation of the person's dysfunctional mast cells. As noted above, triggers may include environmental exposures, certain foods, or excipients in some medication and supplement products. Avoiding such substances and looking for other possible triggers is vital for MCAS patients.


Mold, environmental toxins, and infections can act as triggers and be the syndrome's root cause. For example, suppose mold toxin or Bartonella infection is a root cause and trigger. In that case, identifying and appropriately treating these issues will go a long way to reducing reactivity and restoring health.

You can avoid environmental triggers by eating organic to avoid fertilizers, pesticides (herbicides, insecticides, and fungicides), checking your home for mold, using clean, unscented personal care and cleaning products, reducing EMF exposure by turning off wifi, putting your cell on airplane mode whenever you are not using it, and hard-wiring your home.



   • CALM THE AUTONOMIC NERVOUS SYSTEM


With MCAS, the autonomic nervous system becomes dysregulated. If you have hypersensibilities, it is recommended that you support the nervous system before taking any medicine or supplement to stabilize your mast cells.


Support the nervous system to help your mast cells calm down with different strategies:


   • Retraining the Limbic System. The current programs are very similar; it is an individual choice. I did the Gupta Program, which immensely helped me. The Annie Hooper retraining programhttps://retrainingthebrain.com/annie-hopper/ works better for many people. Now, there is a new program on the market that many people like, Primal Trust; check them out. I am sure any of these will significantly impact your health.  


   Vagus Nerve Stimulation. The vagus nerve is part of your parasympathetic nervous system. It carries electrical signals between your brain and body. Its primary role is to control automatic functions, such as breathing, heart rate, and digestion. That makes it an essential connection between your mind and body. Your vagus nerve helps disengage your sympathetic nervous system — your fight-or-flight response. There are techniques to stimulate the vagus nerve, including breathing exercises, mindfulness, and yoga. Also, check  Stephen Porges Polyvagal Theory. Stanley Rosenberg wrote a book on that: Accessing the Healing Power of the Vagus Nerve, in his book, there are simple exercises you can do or look for online.


   • STABILIZE YOUR MAST CELLS


     • Medications and Supplements


Some patients can get MCAS under control by identifying and then avoiding the substances that are inappropriately triggering activation of their dysfunctional mast cells, plus adopting a healthy diet and lifestyle and supplementation alone. Other patients must use a combination of supplements and medication at least for a while to get their mast cells under control again.


Please always work with your healthcare practitioner to help you figure out which treatment line works best for you.


A wide variety of medications and supplements can help reduce symptoms, either by stabilizing mast cells or blocking the effects of the mediators.


   • Luteolin and Quercetin are the two most studied flavonoids for stabilizing mast cells. They are potent anti-oxidant and anti-inflammatory compounds with mast cell inhibitory actions. Some people don't do well with quercetin but do great with luteolin.

   • Antihistamines, H1 blockers such as Claritin, Zyrtec, Allegra, etc., and H2 blockers such as Pepcid (famotidine) can benefit people with MCAS.

   • Some practitioners use LDN, Xolair, and Leukotriene Inhibitors, such as Montelukast (the brand name is Singulair), to reduce inflammation and prevent mast cell degranulation.

   • Cromolyn and Ketotifen, which are mast cell stabilizers, are also very effective but not as effective as the natural mast cell stabilizers Quercetin and Luteolin, as stated by Theoharis C. Theoharides, BA, MS, MPhil, Ph.D., MD, FAAAAI .

   • DAO Enzyme. DAO breaks down histamine in the gut. DAO enzymes help break down histamine from food.

   • DAO Co-Factors. Including vitamin B-6, Copper, and Zinc.

   • Vitamin C. Known for its antihistamine properties, vitamin C can support the body’s response to histamine.

   • Zeolite. It is a natural clay-like substance. Some studies confirmed the excellent histamine-binding capacity of Zeolite.


   • FOLLOW A LOW-HISTAMINE DIET


If you have histamine intolerance or are experiencing symptoms of histamine intolerance due to MCAS, following a low-histamine diet is recommended. Decrease your histamine bucket by removing high-histamine foods, histamine-liberating foods that may cause histamine release, and DAO enzyme-blocking foods and drinks, including aged cheese, yeast, food leftovers, canned and cured meat, fermented food, vinegar, fermented alcohol, dried fruits, smoked fish, soured foods, and processed foods high in preservatives. Avocados, tomatoes, bananas, citrus, papaya, chocolate, shellfish, wheat germ, alcohol, tea, and yerba mate.


   • FOLLOW AN ANTI-INFLAMMATORY DIET


Due to inflammatory dietary triggers, removing inflammatory foods can help reduce chronic inflammation and mast cell activation. These foods include gluten, dairy, corn, food allergens, refined sugar and carbs, refined oils, artificial ingredients, canned and processed meat, and overly processed foods. Eat lots of organic greens, vegetables, sprouts, herbs, spices, nuts, seeds, organic grass-fed beef, organic pasture-raised poultry and eggs, and wild-caught fish.

Contact me; I can happily help and guide you through these complicated steps. I completely understand you and support you as I, too, have Histamine Intolerance and MCAS



REFERENCES


Luteolin-supplements-All-that-glitters-is-not-gold

https://www.mastcellmaster.com/documents/2023-10/

Mast cells and mast cell mediators as targets of dietary supplements

https://www.mastcellmaster.com/documents/cam-theoharides.pdf

Mast cell activation may explain many cases of chemical intolerance

Claudia S. Miller, Raymond F. Palmer, Tania T. Dempsey, Nicholas A. Ashford and Lawrence B. Afrin.

https://enveurope.springeropen.com/articles/10.1186/s12302-021-00570-3

Quercetin Is More Effective than Cromolyn in Blocking Human Mast Cell Cytokine Release and Inhibits Contact Dermatitis and Photosensitivity in Humans

https://www.mastcellmaster.com/documents/Mastocytosis/Quercetin

Anti-inflammatory and anti-allergic potential of dietary flavonoids: A review

https://www.sciencedirect.com/science/article/pii/S0753332222013348

Luteolin ameliorates inflammation and TH1/TH2 imbalance

https://www.tandfonline.com/doi/abs/10.1080/08923973.2021.1905659

Quercetin inhibits histamine-induced calcium influx in human keratinocyte via histamine H4 receptors

https://www.sciencedirect.com/science/article/abs/pii/S1567576921002563?via%3Dihub

Luteolin Attenuates Allergic Nasal Inflammation via Inhibition of Interleukin-4 in an Allergic Rhinitis Mouse Model and Peripheral Blood From Human Subjects With Allergic Rhinitis

https://www.frontiersin.org/articles/10.3389/fphar.2020.00291/full

Does SIBO Affect Histamine Intolerance and DAO?

https://www.drbenlynch.com/sibo-histamine/



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