Mast Cell Activation Syndrome (MCAS) in Dallas, TX

Mast Cell Activation Syndrome (MCAS) is a complex and relatively newly recognized medical condition that involves the abnormal activation and release of mediators from mast cells. It is important to note that MCAS is distinct from mastocytosis, which is a related condition characterized by the abnormal accumulation of mast cells in tissues. While both conditions involve mast cells, they have different underlying mechanisms and clinical presentations.

In MCAS, mast cells are overly sensitive and easily triggered to release their stored mediators, leading to a variety of symptoms throughout the body. These symptoms can be quite diverse and may affect multiple systems, including the skin, gastrointestinal tract, cardiovascular system, respiratory system, and more. Mast cells produce and store more than just histamine in their granules. There are several pro-inflammatory cytokines (IL-1, proteases (enzymes that break down proteins), leukotrienes, chemokines, prostaglandins, and growth factors. Mediators are substances that are released by mast cells upon activation. These mediators include histamine, leukotrienes, prostaglandins, and cytokines. Histamine, for example, is a well-known mediator that can cause symptoms like itching, sneezing, and inflammation. The process of releasing these mediators is known as degranulation, where the mast cell’s granules (storage compartments) release their contents into the surrounding tissue.


The symptoms of MCAS can vary widely from person to person, may wax and wane, and may include:, 

  • Skin rashes, on and off
  • itching
  • Flushing
  • Abdominal pain
  • Diarrhea, nausea
  • anxiety
  • tinnitus

  • nausea and or vomiting
  • difficulty breathing
  • rapid heart rate
  • headache
  • fatigue
  • insomnia


Diagnosing MCAS can be challenging because its symptoms overlap with many other conditions. The diagnostic process often involves a combination of clinical evaluation, symptom history, and laboratory tests. Elevated levels of certain mediators in blood or urine samples, such as histamine or tryptase, can provide clues, but the diagnosis is typically made based on a combination of clinical judgment and laboratory findings.


Various triggers can provoke mast cell activation in individuals with MCAS. These triggers include allergens, stress, physical exertion, temperature changes, certain medications (such as NSAIDs), infections, and even emotional stress.


Managing MCAS involves a multi-faceted approach.  Antihistamines come in 2 varieties.  H1 antihistamines work on seasonal allergies while H2 antihistamines work on reflux and acid reduction.  You need both type of blockers to completely block histamine effects.

  • Identifying and avoiding triggers is an important part of managing the condition
  • Antihistamines (H1 like cetirizine, hydroxyzine, Diphenhydramine, Brompheniramine, and H2 blockers)
  • mast cell stabilizers (cromolyn, ketotifen, vitamin D)
  • anti-inflammatory drugs such as corticosteroids.

What is Inside Mast Cells?

 Mast cells contain and synthesize much more than just histamine!  MCAS and mast cell degranulation causes a lot more issues than just from histamine.  Mast cells hang out near mucous membranes – respiratory and gastrointestinal tracts but also in loose connective tissues. 

·        histamine (2–5 picograms per mast cell)

·        serotonin (5-HT) – speeds up digestion in gut,
inhibits acid secretion, increases gastric mucus secretion

·        proteoglycans

o  heparin (active as anticoagulant)

o  chondroitin sulfate proteoglycans

o  adenosine triphosphate (ATP)

·        lysosomal enzymes (hydrolytic enzymes) – part
of autophagy

o   serine

§ tryptase – we don’t know function

§ chymase – breaks down many proteins and peptides

§ elastase – breaks down elastin which gives
elasticity to connective tissue (looser sagging skin and tissues), tight
junctions, cytokines.

o  proteases – break down proteins into peptides

o  nucleases – destroy DNA and RNA

o  lipases – breakdown triglycerides into free
fatty acids and glycerol

o  sulfatases/arylsulfatases – break down
components of cell membranes

·        newly formed lipid mediators (eicosanoids): Mast cells convert arachidonic acid into prostaglandins and thromboxanes via surface
COX1 an COX2 (see pathway) on its surface.  These are what are blocked by NSAIDs.

o  Thromboxane – platelet aggregation, arterial

o  prostaglandin D2 – vasoconstrictions and
bronchoconstriction, helps reduce temperature, prevents hair growth

o  leukotriene C4 – pulmonary vasoconstriction and

o  platelet-activating factor

·        cytokines – signaling proteins

o  TNF-α

o  basic fibroblast growth factor

o  interleukin-1

o  interleukin-4

o  stem cell factor

o  chemokines, such as eosinophil chemotactic

·        reactive oxygen species – all unstable, wanting to react with organic tissues and donate energy or electrons. 

o  peroxides

o  superoxide – O2 with an extra electron

o  hydroxyl radical (OH) – damages carbohydrates, nucleic
acids, lipids, and amino acids.

o  singlet oxygen – preferentially interacts with most biomolecules such as lipids, proteins, and DNA/RNA

o  alpha-oxygen

Histamine intolerance

Despite its bad reputation as the instigator of allergies, histamine serves an important role. In the brain, it serves as a neurotransmitter to regulate the wake cycle. Histamine serves to regulate many of our body’s functions. It has effects on hunger, body temperature control, emotions, memory, and the ability to learn by modulating other neurotransmitters in the brain.

Histamine intolerance is a condition in which the body has difficulty breaking down and metabolizing histamine, a chemical compound that is naturally present in the body and is also found in various foods. When histamine levels accumulate in the body due to impaired breakdown, it can lead to a range of symptoms that are like those seen in allergies or allergic reactions. However, histamine intolerance is not the same as a true allergy, as it does not involve the immune system’s response to allergens.

Causes: Histamine intolerance can occur due to various reasons, including a deficiency of the enzyme diamine oxidase (DAO) or histamine-N-methyltransferase (HNMT), both of which are responsible for breaking down histamine. Certain medications, medical conditions, and genetic factors can also contribute to histamine intolerance.  A high intake of histamine containing foods and a high production of histamine by your microbiome can also be responsible.

Symptoms: These symptoms often occur after consuming histamine-rich foods or being exposed to other triggers.  The symptoms of histamine intolerance can vary widely and may include:

  • Headaches/migraines
  • Skin rashes
  • Hives
  • Itching

  • Nasal congestion
  • Sinus problems
  • Gastrointestinal issues (such as abdominal pain, diarrhea, and nausea)
  • Heart palpitations
  • Anxiety

Triggers: Histamine-rich foods can exacerbate symptoms in individuals with histamine intolerance. These foods include aged and fermented products (such as cheese, wine, sauerkraut), processed and smoked meats, certain fruits (like tomatoes, avocados, and citrus fruits), as well as certain vegetables and beverages. Additionally, alcohol, some medications (like NSAIDs), and stress can also trigger symptoms.

Diagnosis: Diagnosing histamine intolerance can be challenging due to its wide range of symptoms and the lack of a definitive diagnostic test. A detailed medical history, symptom analysis, and dietary assessment are often used to make a diagnosis. Elimination diets and keeping a food and symptom diary can help identify triggers.

Treatment: The primary approach to managing histamine intolerance involves:

  • identifying and avoiding triggers.
  • Low-histamine diet
  • Reducing consumption of foods that are high in histamine
  • Avoiding other triggers such as alcohol and stress.
  • Some individuals may benefit from supplements that support histamine metabolism or medications that block histamine receptors.

Treatment with Antihistamines

You will often require both H1 and H2 antihistamines because histamine activates both receptors.

There are many prescriptions and over-the-counter antihistamines. If you have allergies, you are likely taking a H1 antihistamine. First generation H1 antihistamines are NOT recommended due to their sedating effect.  A few examples of first-generation over-the-counter and prescription H1 blockers include:

  • Brompheniramine (Children’s Dimetapp Cold®).
  • Chlorpheniramine (Chlor-Trimeton®).
  • Clemastine (Dayhist®).
  • Cyproheptadine (Periactin®).

  • Dexchlorpheniramine Dimenhydrinate (Dramamine®)
  • Diphenhydramine (Benadryl®).
  • Doxylamine (Vicks NyQuil®, Tylenol Cold and Cough Nighttime®).
  • Hydroxyzine (Vistaril®).
  • Phenindamine (Nolahist®).

Second generation H1 blockers do not cross the blood brain barrier and do not cause drowsiness. Some second-generation H1 blockers include:

  • Azelastine (Astelin®).
  • Loratadine (Claritin®).
  • Cetirizine (Zyrtec®).
  • Desloratadine (Clarinex®).
  • Fexofenadine (Allegra®).
If you are taking an antihistamine to help with gastrointestinal issues, you are likely taking a H2 antihistamine. A few examples of H2 antihistamines include:
  • Cimetidine (Tagamet HB®) – not recommended because it can inhibit DAO.
  • Famotidine (Pepcid®).
  • Nizatidine (Axid®).
  • Ranitidine (Zantac®).

Natural antihistamines

While there are several over the counter and prescription antihistamines that mostly fall into the H1 or H2 histamine blockers, there are several natural ones as well.

Vitamin C: also known as ascorbic acid, is a water-soluble vitamin found in many fruits and vegetables, including citrus fruits, kiwi, cauliflower, melon, tomatoes, strawberries, bell peppers, and broccoli. Vitamin C is a powerful antioxidant and anti-inflammatory that helps reduce histamine levels by acting as a natural antihistamine and stabilizing mast cells. This can help alleviate allergy symptoms such as runny nose, itchy eyes, and wheezing. While it is best to get vitamin C from a balanced diet, supplements are also available.

Bromelain: type of enzyme found in pineapples that has been recognized for its anti-inflammatory properties. One of the lesser-known benefits of bromelain is its potential as a natural antihistamine. Bromelain works by breaking down proteins that cause inflammation and swelling, which can help alleviate allergy symptoms like nasal congestion and sinus pressure. It is available in supplement form, but consuming fresh pineapple may also provide some benefits.

Quercetin: a flavonoid, a plant pigment with antioxidant and anti-inflammatory properties. It is commonly found in apples, dill, asparagus, lettuce, berries, red onions, and black tea. Quercetin is also gaining attention as a natural antihistamine because it can inhibit the release of certain inflammatory chemicals, which can help alleviate allergy symptoms.

Stinging Nettle: also known as Urtica dioica, is a shrub native to Europe, Asia, and North America. While it is often thought of as a pesky weed, stinging nettle has been used for centuries as a natural remedy for a variety of ailments, including allergies. Stinging nettle contains several active compounds that may help alleviate allergy symptoms, including histamine, serotonin, and acetylcholine. It works by inhibiting the production of inflammatory chemicals that cause allergy symptoms like itching and sneezing.

Spirulina: a type of blue-green algae considered a superfood due to its rich nutritional profile. It is also gaining attention as a natural antihistamine. Spirulina contains compounds like phycocyanin and carotenoids, which have anti-inflammatory properties and may help alleviate allergy symptoms. It works by inhibiting the release of histamine and other inflammatory chemicals that cause symptoms such as runny nose, sneezing, and itching. You can take spirulina in supplement form or add it to smoothies and other foods.

Butterbur: known as Petasites hybridus, is a perennial plant native to Europe, Asia, and North America. It is gaining recognition as a natural antihistamine due to its ability to reduce inflammation and inhibit the release of histamine. Butterbur contains compounds called petasins that block the production of leukotrienes, which are inflammatory chemicals involved in the body’s allergic response. Butterbur can help alleviate allergy symptoms like nasal congestion, hay fever, migraines, sneezing, and itching. Butterbur is available in supplement form as well.

Natural Mast Cell Stabilizers

  • Quercetin, Luteolin, Fisertin, EGCG
  • Vitamin D, Resveratrol, Curcumin, honokiol, Sinomenine, Diosmetin
  • Theanine

Low Histamine Probiotic Strains

After many chronic illnesses such as covid-19 and with antibiotic use, it is common for the gut biome to be altered or damaged. Covid-SARS-cov2 directly can damage the gut microbiome. Probiotics are typically required after recovery to restore the beneficial bacteria flora. Some of the bacteria strains that regular probiotics have, can produce histamine themselves. In a histamine overload situation, that is not desirable. These bacterial species listed below will not produce histamine or will help break histamine down in the gut. You do not need every single bacteria species listed, but the probiotic you select should only have species from this list if you are suffering from histamine overload.

  • Bifidobacterium infantis
  • Lactobacillus gasseri
  • Bifidobacterium breve
  • Bifidobacterium bifidum
  • Lactobacillus salivarius
  • Lactobacillus rhamnosus – May help stabilize mast cells and reduce the sensitivity of histamine and allergy-associated receptors while up-regulating anti-inflammatory cells.
  • Bifidobacterium longum – Known to be a histamine degrading probiotic. It may help reduce the post-meal inflammatory response and prevent leaky gut syndrome.
  • Bifidobacterium lactis – May help break down histamine and tyramine.
  • Lactobacillus plantarum – May help break down histamine and tyramine.
  • Saccharomyces Boulardii – helps regulate digestive issues, like diarrhea. Has also been shown in animal studies to increase DAO activity.