EP.384/ MCAS 101 - And What It Has to Do With Endo
Today I am continuing with my series on the trifecta of POTS, MCAS and h-EDS/hypermobile spectrum disorders and how they are connected to endo, and today we are basically doing a little MCAS 101.
What is Mast Cell Activation Syndrome?
MCAS is a condition (though is now being debated as a group of disorders) caused by over-active mast cells that release high levels of inflammatory mediators (chemicals) including histamine. Mast cells are immune cells that are like guards stationed around the body, ready to respond to a threat, injury, etc. They release inflammatory chemicals in response to these perceived threats, but in MCAS, these guards are extra jumpy and extra cautious, and fire off at normal stimuli, it could be the food you eat, your environment, stress or more.(1)
These inflammatory mediators cause a range of allergic and inflammatory type full body symptoms ranging from gastrointestinal symptoms to heart symptoms such as a racing heart and chest pain, to skin reactions and cognitive difficulties.
Whilst not a new disease, it was only ‘discovered’ in 2007 and is only more recently getting attention due to the increase in prevalence since covid, affecting those who have developed long covid and POTS post covid, which I see as very common in our endo demographic. In fact, a 2025 systematic review and meta-analysis showed a significant increase in long covid in those with endometriosis vs. those without.(2) In general, females, especially those with immune related conditions, are more at risk of long covid.(3)
The general population MCAS rates were originally thought to be about 17% (4), based on the German population, but experts are now estimating numbers to be much higher since covid, as covid activates mast cells in those who already have MCAS or have a predisposition to develop the condition.(5)
Diagnosis can be difficult due to diagnostic criteria which requires elevated levels of certain inflammatory markers that many with MCAS actually do not have, but more recent research is proposing a more inclusive diagnostic criteria.(6)
Additionally, not many doctors are yet aware of MCAS, how to diagnose it, or do not have access to the right testing. As a result, MCAS is often diagnosed based on symptoms and improvement with mast cell stabilising and antihistamine treatment (it’s important to note, people respond differently to the various types, so it’s about finding the right combo for each person).
The Symptoms
Symptom severity and the range of symptoms will vary from person to person - this is because mast cells release over 1200 different inflammatory mediators(7), and not all at the same time or in the same circumstances, and so the impact of these inflammatory mediators will depend on the type of mediators released. Additionally, symptoms will vary even to the same trigger and this can be to do with where you are in your cycle (oestrogen increases mast cell activity)(8), what other environmental triggers you’ve been exposed to (may be unknowingly), your current stress levels (stress increases mast cell degranulation)(9) and so on.
Symptoms include(10):
Flushing
Hives
Skin itching
Throat tightening feeling
Rhinitis
Sinus issues/congestion
Trouble breathing/shortness of breath - not life-threatening but feels it (unless anaphylaxis)
Headaches
Brain fog
Fatigue
Mental health issues - commonly anxiety but clinicians and patients report OCD and depression (especially treatment resistant types)
Chest pain
Racing heart
Palpitations
Feeling faint
Dizziness and vertigo
MCAS and endometriosis
We don’t yet have data on endometriosis and MCAS specifically, but we do know that mast cells play a key role in the development of endometriosis, and are found in higher levels, and more sensitive (so are extra reactive and firing off inflammatory chemicals) in endometriosis lesions and pelvic fluid.(11)
Endometriosis patients also have altered immune dysfunction, which of course, mast cells are part of(12), and a higher prevalence of allergies, with various research showing(13):
61% of people with endo have been found to have allergies.
People with endometriosis are significantly more likely to have a family history of allergies.
People with endo have been found to be four times more likely to have allergies.
People with endo have an increased risk of eczema, hives, asthma and hayfever.
These findings possibly suggest that the over activity of mast cells is not just limited to the endo lesions, but is more likely to be a systemic issue, given that mast cells and histamine govern allergic responses.
We also know that endometriosis significantly increases our odds of also having hEDS/HSD or POTS, as we've explored in previous episodes.(14)
POTS and hEDS/HSD are part of a triad of POTS, hEDS (or HSD) and MCAS, and frequently present together both clinically and in the research.(15)
Research has found:
31% of POTS patients had hEDS and 55% had generalised joint mobility.(16)
Out of almost 38,000 patients, nearly 1 in 3 MCAS patients also had hEDS.(17)
64% of POTS patients demonstrated MCAS type symptoms and out of those, 66% showed elevated markers consistent with MCAS (though remember, markers are controversial because not all MCAS patients have the same elevated markers, if any).(18)
Many doctors and experts specialising in one or all of these conditions, acknowledge that endometriosis is often also seen in these patients. In fact, Dr Gall, who was my cardiologist who diagnosed me with suspected kounis syndrome, suspected MCAS, dysautonomia and mild hypermbolity, said to me that the majority of patients he sees are young to middle aged women with endometriosis, SIBO, POTS, hEDS or HSDs, MCAS, and interstitial cystitis, with worsening or new conditions post covid.
The Triad
Evidence is building and some researchers are theorising that mast cells are the thread that connects all of these conditions, as the inflammatory mediators can have an impact on all three conditions, triggering symptoms and worsening the conditions.(19)
So, if you’re listening, and you think this could possibly sound like you, first of, I want to say MCAS sucks, it’s one of the most awful things I’ve had to face, but it can get better and I am so much improved to where I was about five years ago, when I couldn’t eat a meal or walk across the room without crippling chest pain, shortness of breath and dizziness.
I’ve have a lot of episodes on MCAS and histamine issues, so feel free to dive into those, but I will be doing episodes on how to get diagnosed and what to do if you can’t, and management strategies for MCAS as well root causes and how to resolve them, but as I said, I do have a number of these across the years.
Of course, if you don’t want to work this all out on your own, you can reach out to me for a single session, or you can book in for a free hour-long consultation to see if my year long coaching is the right fit for you.
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References
1) https://med.virginia.edu/ginutrition/wp-content/uploads/sites/199/2020/06/Mast-Cell-Activation-Syndrome-June-2020.pdf, https://pubmed.ncbi.nlm.nih.gov/32324159/
2) https://pmc.ncbi.nlm.nih.gov/articles/PMC12079877/
3) https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2829454, https://jamanetwork.com/journals/jama/article-abstract/2828511
4) https://pubmed.ncbi.nlm.nih.gov/24098785/
5) https://pmc.ncbi.nlm.nih.gov/articles/PMC8459548/, https://www.sciencedirect.com/science/article/pii/S1201971220307323
6) https://pubmed.ncbi.nlm.nih.gov/34166845/, https://pubmed.ncbi.nlm.nih.gov/35623575/, https://pubmed.ncbi.nlm.nih.gov/32324159/
7) https://braininflammation.org/mast-cell-activation-syndrome-mcas-dr-lawrence-afrin/
8) https://pmc.ncbi.nlm.nih.gov/articles/PMC1797832/ , https://pmc.ncbi.nlm.nih.gov/articles/PMC2603032/
9) https://pubmed.ncbi.nlm.nih.gov/7588332/
10) https://med.virginia.edu/ginutrition/wp-content/uploads/sites/199/2020/06/Mast-Cell-Activation-Syndrome-June-2020.pdf, https://www.degruyterbrill.com/document/doi/10.1515/dx-2020-0005/html
11) https://pubmed.ncbi.nlm.nih.gov/29074615/,https://pmc.ncbi.nlm.nih.gov/articles/PMC9945179/,https://pubmed.ncbi.nlm.nih.gov/36016927/,https://pubmed.ncbi.nlm.nih.gov/15494048/,https://pubmed.ncbi.nlm.nih.gov/27841046,https://pubmed.ncbi.nlm.nih.gov/26550518/,https://pubmed.ncbi.nlm.nih.gov/17631002/,https://pubmed.ncbi.nlm.nih.gov/40028674,https://pubmed.ncbi.nlm.nih.gov/34630429/,https://pmc.ncbi.nlm.nih.gov/articles/PMC6964357/, https://pubmed.ncbi.nlm.nih.gov/37664916/
12) https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1727183/full
13) https://pubmed.ncbi.nlm.nih.gov/22369407/, https://pubmed.ncbi.nlm.nih.gov/24857310/, https://www.nichd.nih.gov/newsroom/releases/endometriosis, https://www.ejog.org/article/S0301-2115(14)00234-6/abstract
14) https://pubmed.ncbi.nlm.nih.gov/39990556/, https://jchr.org/index.php/JCHR/article/view/5363, https://pmc.ncbi.nlm.nih.gov/articles/PMC3413773/
15) https://pmc.ncbi.nlm.nih.gov/articles/PMC11348541/, https://med.virginia.edu/ginutrition/wp-content/uploads/sites/199/2020/06/Mast-Cell-Activation-Syndrome-June-2020.pdf
16) https://pmc.ncbi.nlm.nih.gov/articles/PMC7282488/
17) https://ard.bmj.com/content/80/Suppl_1/965.1, https://pubmed.ncbi.nlm.nih.gov/35449490/, https://pmc.ncbi.nlm.nih.gov/articles/PMC9022617/
18) https://www.ahajournals.org/doi/10.1161/JAHA.121.021002?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
19) https://pmc.ncbi.nlm.nih.gov/articles/PMC11348541/#sec14