Mast cell activation syndrome (MCAS) is a common yet under-recognized condition. In MCAS, a person has frequent allergy reactions (e.g., hives, wheezing, nausea) to multiple environmental substances, including foods, medications, and scents. Next week (9/27), Richard G. Boles, M.D. will be presenting his research findings in 25 patients with MCAS at the at the Mast Cell Masterminds Conference in Hood River, Oregon. All but one of his patients (24/25) had significant variants in ion channel or energy metabolism genes. Treatment aimed at these pathways is oftentimes highly effective.
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Mast cell activation syndrome (MCAS) is a relatively common condition that many people have not heard about, and of which many physicians remain uninformed. MCAS is common in people with chronic fatigue, gastrointestinal (GI) symptoms, dysautonomia/POTS, and/or joint hypermobility. Thus, MCAS is likely present in many of the people (or their relatives) who order from NeuroNeeds®. This blog explains what MCAS is, and what can be done if you suspect that you, or someone you know, might have it. This blog will also summarize Dr. Boles’ exciting new data on the potential causes of MCAS.
Mast cells are the white blood cells that cause immediate allergic reactions. When a foreign substance binds IgE (the allergy type of antibody) present on the mast cell surface, this results in the release of many chemicals (“mediators”) from the mast cell. These mediators cause the symptoms of the allergic reaction. The purpose of IgE and mast cells is to attack infection, especially parasites. However, this system can be activated on occasion in normal people by a variety of different of foreign substances, such as pollen.
People with MCAS suffer frequent and serious reactions of anaphylaxis (severe allergic-like reactions) to multiple environmental substances. There is more than one diagnostic criteria for MCAS, and this is a controversial area among physicians. Some diagnostic criteria require laboratory evidence of mast cell overactivation. When these tests are negative or not performed, yet the person has allergic reactions to a very large number of compounds, the diagnosis is sometimes stated as mast cell activation disease (MCAD).
People with MCAS/MCAD have anaphylaxis to multiple substances, including many different foods, medications/supplements, and scents (e.g., cleaning fluids, perfume, candles). Anaphylaxis can manifest in the skin (e.g., hives, swelling), airways (e.g., difficulty breathing, wheezing/asthma), GI tract (e.g., diarrhea, nausea, cramping/pain), and/or autonomic nervous system (e.g., fast heart rate, fainting/POTS).
The cause of MCAS/MCAD is hyperactive mast cells, and most therapies are directed at calming mast cells. However, why do some people have such hyperactive mast cells?
In a paper published in 2023 (PMID 37234784, https://pubmed.ncbi.nlm.nih.gov/37234784), Dr. Boles and his research group studied 80 of his patients with cyclic vomiting syndrome (CVS) and found that almost all had significant variants in 22 nuclear genes and/or in the mitochondrial DNA (mtDNA) genes (https://www.neuroneeds.com/whole-exome-genome-sequencing-in-cyclic-vomiting-syndrome). CVS was chosen by Dr. Boles to study as a model functional disorder as most patients also have many other functional conditions, including migraine, other chronic pain disorders, chronic fatigue syndrome, POTS, and/or GI dysmotility. MCAS/MCAD overlaps greatly with those other conditions, so Dr. Boles investigated whether the same 22 CVS genes plus mtDNA are common in MCAS as well.
Many MCAS/MCAD patients have been referred to Dr. Boles recently for whole genome sequencing (WGS, all of the DNA). Dr. Boles reviewed his records to identify the most recent 25 patients he has evaluated with MCAS/MCAD who had WGS. He will be presenting his findings next week (September 27) at the Mast Cell Masterminds Conference in Hood River, Oregon. In summary, a full 22 of the 25 patients (88%) have a significant genetic variant (that likely alters protein function) in one of those 22 (nuclear) + mtDNA genes. [See the full paper on CVS for a discussion of what constitutes a “significant” variant.]
Among the 22 nuclear CVS-associated genes, ion channel genes were most common, whereas 18/25 (72%) have a significant variant. The specific channel genes most associated with MCAS/MCAD were CACNA1A, SCN4A, and SCN9A (4 patients each), and SCN10A (3 patients) – two calcium and two sodium channels. Some MCAS/MCAD patients had significant variants in other channel genes that were not in the CVS study, including in chloride, potassium, and magnesium channels. When those were added, 21/25 (84%) of the patients had a significant variant in an ion channel gene. Mast cells are well known to be activated by calcium, and variants in channel genes likely predispose towards disease via increasing calcium levels.
A significant mtDNA variant was identified in 12/25 (48%) of the patients. All but one patient (24/25, 96%) have a significant variant in the mtDNA or in any one of the channel genes in the previous paragraph. Ion channels and energy metabolism are highly-related pathways, and many patients have a significant variant in both.
On the other hand, a significant variant in a gene involved in the immune system or inflammation was only noted in 10/25 (40%) of the patients.
While these results are preliminary, they do suggest that physicians should look beyond the immune system for determinants of MCAS/MCAD, particularly to ion channel and mtDNA/energy metabolism genes. This fits Dr. Boles’ clinical experience in that disease manifestations of MCAS/MCAD often improve, sometimes dramatically, on dietary supplements aimed at ions and energy metabolism.
In his MCAS/MCAD patients, Dr. Boles recommends the “Brain Bundle” (https://www.neuroneeds.com/product/brain-bundle): EnergyNeeds®, QNeeds®, and OmegaNeeds. In individuals, unable to swallow capsules, SpectrumNeeds® can be substituted for EnergyNeeds® in the Brain Bundle. The common mantra to “start low, go slow” is of particular importance in people with MCAS/MCAD given their sensitivities to many different compounds. In cases whereas combination supplements are not tolerated, sometimes individual supplements are.
Most doctors are not well informed regarding MCAS/MCAD and how to best treat it. However, there are many experts across the United States. The speaker list at next week’s conference in Oregon (https://www.mastcellmasterminds.com/schedule) provides a Who’s Who list on many of the experts.
Disclosures:
Dr. Boles is the Chief Medical & Scientific Officer for NeuroNeeds LLC, the company that makes products such as SpectrumNeeds®, EnergyNeeds®, QNeeds®, and CalmNeeds®. As such, he may receive financial compensation based upon by efforts and/or the success of the company. You are under no obligation to purchase this or any products, whether recommended by Dr. Boles or another health care provider. As always, it is recommended that you contact your physician regarding these products and all other changes to disease management.
The Content within this article and NeuroNeeds Blog is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this Blog.