Novel Treatments for Mast Cell Activation Syndrome

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Mast cells serve an important purpose in our immune systems. Located in just about all bodily tissues, they are present in large amounts within connective tissue, reproductive organs, the nervous and cardiovascular systems, skin, and the intestinal lining. Mast cells respond to perceived threats by secreting chemical mediators such as histamine, interleukins, prostaglandins, cytokines, and chemokines. This results in physiological changes including inflammation, increased mucous production, and smooth muscle contraction.

While this cascade of events is a protective mechanism that aids in healing, it is also a good example of how “too much of a good thing” can cause harm. When mast cells become chronically activated or overactive, it can affect many organs and body systems, leading to a multitude of frustrating and debilitating symptoms.

More people than ever before – possibly as high as 17% of the population –are said to have this problem, which is now referred to as mast call activation syndrome (MCAS). Some experts hypothesize that the large toxic load we now carry due to environmental exposures is one of the main contributors to the growing number of individuals affected my mast cell disorders.

Symptoms typical of mast cell activation syndrome include (but are not limited to):

  • cognitive dysfunction or “brain fog”
  • mood disorders (anxiety/depression)
  • itching/rashes
  • chronic fatigue
  • fluid retention/edema
  • flushing
  • abdominal pain

MCAS often goes hand in hand with postural orthostatic tachycardia syndrome (POTS) in that they have many overlapping symptoms. Additionally, POTS is often thought to lead to the development of MCAS in some individuals. Other disorders and diseases that have been linked with MCAS are autoimmune diseases, allergies/asthma, fibromyalgia, chronic fatigue syndrome, GERD, irritable bowel syndrome, food intolerances, migraines, and interstitial cystitis, just to name a few.


Mast cell disorders can be tricky to diagnose since mast cell activity occurs mainly locally within the cell, meaning that blood tests (and even urine tests) are not always sensitive enough. Nevertheless, there are several lab tests that may be helpful in obtaining a diagnosis, including:

  • Serum tryptase
  • Serum chromogranin A
  • Plasma histamine
  • Plasma PGD2
  • Plasma heparin
  • PGF2a
  • PGD2 (urine)
  • N-methyhistamine (24-hour urine test)

Because of the lack of definitive tests for MCAS, clinical symptoms – episodes consistent with mast cell mediator release affecting two or more organs or systems – are also part of the diagnostic criteria, as is positive response to treatment. Another option for testing that is sometimes more affordable (especially if gastrointestinal biopsy has been previously done) is to look for mast cells directly in GI cell samples.



There are a wide variety of medications used to treat MCAS, including mast cell stabilizers, H1 and H2 blockers, leukotriene inhibitors, and tyrosine kinase inhibitors. Since the syndrome can affect so many different organs and body systems, different medications can be used for specific symptom management. For example, analgesics may be given for headaches, proton pump inhibitors for digestive complaints, and amphetamines for interstitial cystitis.

Diet and Lifestyle

Although not a long-term solution, avoiding triggers can be helpful in minimizing symptoms. Triggers vary from person-to-person, but some common ones include infections such as Lyme disease and co-infections, small intestine bacterial overgrowth (SIBO), exposure to mold, chemicals and strong odors, temperature extremes, and certain foods and medications.

Limiting dietary histamine can be very helpful as well. Foods that contain high levels of histamines (or which trigger the release of histamines) include leftovers, seafood (unless it’s very fresh), smoked or cured meats, aged cheeses, yeast, alcohol, black tea, food additives, and nightshades (ie. chili powder, cayenne pepper, tomato products).

Certain dietary supplements have also shown promise in MCAS when used in the context of an integrative approach to treatment. Some of these include:

  • Adrenal support – DHEA, ashwagandha
  • Natural mast cell stabilizers – ascorbic acid, quercetin, omega-3 fatty acids, vitamin B6, alpha lipoic acid, and N-acetyl cysteine
  • Histamine-degrading enzyme called DAO (taken with meals)
  • Gut healing nutrients – probiotics (specifically bifidobacter species and L. rhamnosus), zinc, glutamine

Novel treatments

Even with all these options for treatment, many individuals continue to struggle with symptoms. Being that MCAS sufferers can be sensitive to many different stimuli, they often have trouble finding medications and treatments that are well tolerated.

Recently a case study was published on a 43-year old female with severe POTS, MCAS, and small intestine bacterial overgrowth (SIBO). After being sick for over 20 years and failing many treatments, she was put on a novel protocol which included immune therapy with IV immunoglobulins (IVIg), low dose naltrexone (LDN), and 2 weeks of antibiotics (to treat the SIBO). She had remarkable and sustainable results. This is the first documented case where IVIg was used in MCAS and only the second on its use for POTS. LDN and IVIg both work by regulating T-cell lymphocytes and reducing cytokine production which is effective for treating the faulty mast cells. LDN also works by producing endorphins which help with a variety of the underlying mechanisms including improved gut motility, which in turn helps to prevent SIBO from returning.

For more information on mast cell disorders, refer to the work of Dr. Lawrence Afrin including his book, “Never Bet Against Occam: Mast Cell Activation Disease and the Modern Epidemics of Modern Illness and Medical Complexity.” He is a leading expert in this area.

Since mast cell activation syndrome can be a component of so many illnesses that are chronic, debilitating, and involve such a wide variety of symptoms, it is encouraging to see it getting more attention in recent years. We now have a greater understanding of how these complex and seemingly unrelated symptoms tie together and point to one common mechanism gone awry.




About Holtorf Medical Group

The Holtorf Medical Group specializes in optimizing quality of life and being medical detectives to uncover the underlying cause of symptoms, rather than just prescribing medications to cover-up the symptoms. We are experts in natural, prescription bioidentical hormone replacement and optimization, complex endocrine dysfunction, fibromyalgia, chronic fatigue syndrome and Lyme disease.

We’ve dedicated our practice to providing you the best in evidenced-based, integrative medicine that’s not only safe and effective, but provides measurable results.