Is MCAS More Common in POTS and hEDS? Why the Numbers Disagree
Estimates of MCAS in POTS run from 2% to 87%, depending on the criteria used. What the Mayo research argues, and what it doesn't say about your diagnosis.
Photo: Europeana / Unsplash
Is mast cell activation syndrome (MCAS) more common in people with postural orthostatic tachycardia syndrome (POTS) or hypermobile Ehlers-Danlos syndrome (hEDS)? It depends on how MCAS is defined, and that choice is a big part of why the published numbers disagree. In a 2025 study of the records of 100 young patients with POTS, the share who met criteria for MCAS was 2% under the strictest definition, 37% under a less strict, lab-based definition, and 87% under the loosest. The patients stayed the same, and only the definition changed.
MCAS is a condition in which mast cells, the immune cells that release histamine and other chemicals during a reaction, release those chemicals too easily. POTS means your heart rate climbs too far when you stand up. hEDS is an inherited connective tissue condition with very flexible joints. Clinicians see the three in the same person often enough that many call them a triad.
How the definition changes the count
To count how many people with POTS also have MCAS, researchers first have to pick from competing sets of criteria. The stricter definitions ask for lab evidence that mast cell chemicals went up during symptoms. A 2025 expert review from the American Gastroenterological Association (AGA) describes one version of that test: a blood tryptase level (tryptase is an enzyme mast cells release) drawn at baseline and again 1 to 4 hours after a flare, with a rise of 20% above baseline plus 2 ng/mL needed to show mast cell activation. Looser definitions rely more on the pattern of symptoms and on whether treatment helps. As I've said on video, "the research case for tight diagnostic criteria is reasonable," and narrow criteria are "good for research and bad for patients whose real disease doesn't match the template."
A 2025 study by Yao and colleagues in Frontiers in Neurology shows how much that choice changes the answer. Out of 392 patients aged 8 to 25 with orthostatic intolerance, 100 met POTS criteria, and 80% of them were female. Using a modified version of consensus-1 criteria, 2% had MCAS. Using what the authors called conservative consensus-2 criteria, which emphasize lab confirmation, 37% did. Using clinical criteria regardless of lab support, 87% did. Only 69 of the 100 patients could get the mast cell lab tests at all, often because of insurance or because they couldn't find a lab that ran them, so the stricter counts could only come from that group. The authors reported that patients diagnosed by clinical criteria responded to MCAS treatment similarly to those diagnosed with stricter criteria, and they concluded that overly strict criteria miss opportunities for potential treatment.
That study has limits. It looked back through existing records, and in their limitations section the authors acknowledged that basing the loose criteria partly on treatment response, then reporting a high response to treatment, could be seen as circular reasoning. They also disclosed that the corresponding author helped write the consensus-2 criteria.
A 2026 meta-analysis by Kulin and colleagues reviewed 19 studies of people with POTS. Its MCAS figure came from three of those studies, covering 4,022 people: 36.3% reported MCAS, although the actual figure could plausibly sit anywhere from under a fifth to three in five. In their limitations section, the authors noted that most of the MCAS data were self-reported, so the condition could have been either under- or overreported. A self-reported diagnosis doesn't tell you which criteria were used to make it.
What the Mayo researchers argue
In 2025 and 2026, allergy and immunology researchers at Mayo Clinic published two papers on whether MCAS is more common in POTS and Ehlers-Danlos syndrome (EDS), and both say the evidence for a higher rate is lacking. Co-occurring isn't the same as caused by, and "these conditions cluster" is a different claim from "a third of people with POTS have MCAS."
In 2025, Farley and colleagues at Mayo Clinic Arizona published a systematic review in the Annals of Allergy, Asthma & Immunology. They reviewed 92 full texts, looking for studies in which people with POTS and/or EDS had a mast cell activation disorder, or a related inherited trait called hereditary alpha-tryptasemia, diagnosed by the criteria the reviewers had set in advance. No study met that bar. They concluded that their review did not find evidence to confirm a relationship, noted that one study came close to meeting full diagnostic criteria for MCAS, and called for research using strict and validated criteria to clarify whether a true association exists. A review that finds no qualifying studies is a finding about the research done so far, and these reviewers asked for better studies rather than declaring the question closed.
In August 2026, a Mayo Clinic group including several of the same authors published a paper in The Journal of Allergy and Clinical Immunology: In Practice titled "Lack of evidence for increased mast cell activation syndrome prevalence in postural orthostatic tachycardia syndrome and/or hypermobile Ehlers-Danlos syndrome."
Which criteria the Mayo researchers used
It helps to know what yardstick these reviews used. The same Mayo group has also studied MCAS videos on TikTok. In a 2026 paper, they took the 50 most-watched MCAS videos from a June 2024 search and checked each one for the Vienna criteria, another name for consensus-1. Only one of the 50 included them, and the authors rated most of the videos as containing misinformation, including about diagnostic criteria. Their yardstick for the right diagnostic criteria is consensus-1. Very few studies in POTS or hEDS have used consensus-1, so "not enough evidence" mostly means not enough studies that used the strictest definition. If you have MCAS along with POTS or hEDS, these papers don't make your diagnosis wrong.
There is a second set of criteria, called consensus-2. A large group of clinicians who treat MCAS published consensus-2 in 2020. It accepts more kinds of mast cell lab tests, and it lets a good response to treatment count toward the diagnosis. Its authors wrote that, until careful research gives more definite answers, a diagnosis made with either set of criteria is valid, reasonable, and helpful. In the Yao study above, patients diagnosed with broader criteria responded to treatment about as well as patients diagnosed with stricter ones. The major allergy societies use criteria built on consensus-1, which is part of why the numbers in this debate disagree so much.
Strict criteria are built to be very sure of a diagnosis, and being very sure is what a research study needs. In clinic, the question is different. The question there is whether you have the condition, and whether treatment can help you. Broader criteria like consensus-2 were written for that question.
Where I stand
MCAS, POTS, and hEDS can happen in the same person. One person can also have just one of them without the others, and having one doesn't mean you have all three. So I don't think a diagnosis of one is enough reason, on its own, to test for the other two right away. Testing makes sense when you have symptoms that point to one of them, which is close to what the AGA review advises.
In my own practice, I lean toward consensus-2. When the workup has been done properly, the other possible causes have been ruled out, and MCAS fits how you're presenting, I'll diagnose by consensus-2 rather than consensus-1. I don't think anyone is making this up, and not meeting the strictest criteria doesn't mean nothing can be done. Gatekeeping a diagnosis does real harm when it leaves a patient with nothing. My priority is that you feel heard, that what you're living with is taken seriously, and that we find something that helps.
Why the three conditions keep getting discussed together
In my own teaching, I've explained the triad through connective tissue. In hEDS the tissue tends to be more fragile and stretchy, and that may make the environment mast cells live in more reactive, especially in idiopathic MCAS, where no genetic mast cell defect is found. This is a working explanation. The AGA review describes the links between these conditions as observed associations and notes that experimental evidence for the mechanisms is limited and evolving.
The other half of what I teach is the differential diagnosis. As I put it in one video, "some symptoms that resemble mast cell activation may actually be driven by other conditions that require different types of treatment." The same caution applies to a single lab value, which is why a low DAO result isn't a diagnosis on its own.
If you have POTS or hEDS and wonder about MCAS
The AGA review, written for gastroenterologists, advises targeting MCAS testing to people with symptoms of it, and states that testing everyone with hEDS or a hypermobility spectrum disorder isn't supported by current evidence. The symptoms it lists come in episodes and involve two or more body systems, such as flushing, hives, itching, wheezing, a racing heart, cramping, nausea, or diarrhea.
Three things to bring when you raise this with your clinician:
- Notes on each episode: what happened in your skin, gut, breathing, and heart, and when
- Whether a tryptase can be drawn shortly after a flare and compared with a baseline value
- What else could explain the symptoms, so the workup covers the alternatives too
More on diagnosis is collected on the MCAS hub.
If you're living with MCAS and want a structured starting point, MCAS: What You Need to Know First walks through what the diagnosis actually means, where to begin, and what to do when diet alone isn't enough.
FAQ
Do POTS or hEDS cause MCAS?
That hasn't been established. The AGA's 2025 expert review describes the links between hEDS, POTS, and MCAS as observed associations, and notes that experimental evidence for the biological mechanisms is limited and still evolving. Co-occurring and causing are different claims: researchers still disagree about how often these three conditions show up together, and causation hasn't been shown.
Why do different sources give such different MCAS rates in POTS?
Because they use different definitions of MCAS. In one 2025 study of the records of 100 young patients with POTS, the share meeting criteria for MCAS was 2% under a modified version of consensus-1 criteria, 37% under conservative consensus-2 criteria, and 87% under clinical criteria. A number quoted without its definition can't be compared with another one.
Does the Mayo Clinic research mean my MCAS diagnosis is wrong?
No. A prevalence argument is about a population statistic, meaning how often MCAS shows up across groups of people with POTS or hEDS, so it can't tell you whether your own diagnosis is right. If yours was made against criteria, with symptoms in more than one body system, a population argument doesn't change it.
Should everyone with hEDS or POTS be tested for MCAS?
The AGA's 2025 expert review says testing everyone with hEDS or a hypermobility spectrum disorder for MCAS isn't supported by current evidence. It recommends targeting testing to people with episodes of symptoms in two or more body systems, such as flushing, hives, wheezing, a racing heart, or cramping. Whether testing fits your situation is a question for your clinician.
What counts as lab evidence of mast cell activation?
One common standard compares a blood tryptase level drawn 1 to 4 hours after a flare with a baseline value. The AGA review describes a rise of 20% above baseline plus 2 ng/mL as the amount needed to show mast cell activation. Urine tests for other mast cell chemicals can also be done, usually through an allergy specialist.
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