If you have hypermobile EDS, there’s a good chance you’ve never been properly tested for something called Epstein-Barr virus, or EBV. Most people have heard of it only as “the virus that causes mono.” But there’s a growing amount of solid research showing EBV can do a lot more than cause mono and if you have hEDS, you may be more at risk of dealing with its aftereffects.

Let me walk through what the science actually shows:

Almost everyone has this virus already

Here’s the surprising part: more than 95 out of every 100 adults have been infected with EBV at some point in their life. For most people, that infection happened so mildly in childhood that nobody even noticed. Others got a full case of mono as a teenager or young adult.

Either way, once you’ve had EBV, it never actually leaves your body. It goes to sleep, doctors call this “latent”, hiding quietly inside certain immune cells for the rest of your life. For most people, it just stays asleep forever and never causes another problem.

But sometimes it wakes back up. This is called reactivation, and it tends to happen when the body is under a lot of stress or when the immune system isn’t working the way it should.

When EBV reactivates, it usually doesn’t cause the classic mono symptoms like a sore throat and swollen glands. Instead, people tend to describe things like ongoing tiredness, brain fog, and muscle aches, symptoms that are easy to blame on a dozen other things, which is exactly why reactivation so often goes unnoticed.

Autoimmune diseases and hEDS

Autoimmune disease shows up more often in the hEDS population than researchers used to appreciate, largely because hEDS carries with it a real degree of underlying immune dysregulation, not just joint and tissue laxity. Studies have found that a substantial share of hEDS patients also carry an immunoglobulin deficiency, mast cell activation disease, or both, and separate research has shown hEDS patients are more likely to develop prolonged post-viral syndromes like Long COVID, particularly when POTS, mast cell symptoms, or chronic fatigue are already part of the picture. That combination of an already unbalanced immune system and a higher susceptibility to lingering viral activity is likely part of why autoimmune conditions cluster more heavily in this population than in the general public.

Can this virus actually cause autoimmune disease?

This is the question researchers have been digging into hard over the last couple of years, and the short answer is: for some conditions, yes, and the evidence is stronger than most people realize. But it’s not equally strong across the board.

Multiple sclerosis (MS) has, by far, the strongest link to EBV of any autoimmune disease. Studies have found that nearly every single person who later develops MS already had antibodies to a specific EBV protein before they ever showed a single symptom. Researchers have even figured out why: a small piece of that EBV protein happens to look almost identical to three different proteins found in human nerve tissue. When your immune system builds an army of antibodies to fight off the virus, some of those antibodies get confused and start attacking your own nerve tissue instead, because it looks so similar. Scientists call this “molecular mimicry”, basically, mistaken identity.

Lupus also has a strong connection. Research shows that when EBV reactivates, it’s associated with people going on to develop active lupus. The mistaken-identity mechanism is similar, just involving a different part of the same viral protein.

Rheumatoid arthritis has a believable connection too, but the research isn’t quite as solid or consistent yet as it is for MS and lupus.

Hashimoto’s thyroiditis is the weakest link of the bunch. There’s some early research looking into it, but it’s much less established than the others. I wouldn’t put too much weight on this one yet.

So, bottom line: this isn’t a made-up connection. For at least MS and lupus, the evidence that EBV plays a real role is quite strong.

Why this matters even more if you have hEDS

Here’s the part that’s specific to the hEDS community. hEDS used to be thought of as just a “loose joints” disorder. But research over the last several years has shown it’s also, for a lot of patients, a disorder where the immune system doesn’t behave the way it’s supposed to. A few things worth knowing:

·      One study looked at people with hEDS and found that 43 out of 100 had a documented deficiency in their antibodies (the proteins your immune system uses to fight things off). About 10 out of 100 also had MCAS, and that number jumped to 19 out of 100 when combined with an antibody deficiency. In other words, a lot of hEDS patients are dealing with more than one immune issue at the same time.

·      Several other studies have found that a majority of hEDS patients, in some studies, as many as 72 out of 100, have overly reactive mast cells, compared to only about 14 out of 100 in people without hEDS. These same studies found hEDS patients get more frequent infections in general.

·      A large 2025 study looking at over 23 million patient records, including nearly 30,000 people with hEDS, found that hEDS is more common than doctors used to think, roughly 1 in every 800 people (and it likely even more common than this). That same study found hEDS patients were significantly more likely to develop Long COVID than people without hEDS, and that risk was highest specifically among those who also had POTS, mast cell issues, or chronic fatigue. The researchers even raised the idea that a lingering viral immune response might be part of what’s driving hEDS symptoms in some patients.

Put simply: if you have hEDS, your immune system is statistically more likely to already be running a little “hot” or unbalanced, whether that’s from low antibody levels, an overactive mast cell response, or a tendency to struggle with recovering fully from viral infections. That’s exactly the kind of internal environment where a sleeping virus like EBV is more likely to wake back up. And every time it wakes up, it’s another chance for that “mistaken identity” process to nudge your immune system toward attacking your own body.

I want to be upfront: nobody has yet done a big study measuring EBV reactivation specifically in hEDS patients versus people without hEDS. That study needs to happen. What we have right now is two separate, well-supported sets of research, one showing hEDS patients tend to have more immune system problems, and another showing immune system problems make EBV reactivation (and the autoimmune risk that comes with it) more likely. Put those two things together, and testing starts to make a lot of sense, even without one single study proving the whole chain.

How to actually get tested for this the right way

Here’s something important: the standard “mono test” most doctors run only checks for a brand-new infection. It won’t tell you anything about whether an old infection has woken back up. To check for reactivation, you need a more complete blood panel that looks at four different markers:

·      VCA IgM - shows up with a brand-new infection. Not useful for reactivation.

·      VCA IgG - becomes positive after any past infection and stays positive for the rest of your life. On its own, this just tells you that you’ve had EBV at some point, nothing more.

·      EBNA-1 IgG - shows up a few weeks to months after a first infection and also stays positive for life.

·      Early Antigen (EA-D) IgG - this is the one that matters most for reactivation. It can go up when the virus wakes back up, though it can also stay positive for years in some perfectly healthy people, so it’s a helpful clue rather than definite proof by itself.

A pattern that looks like reactivation is: VCA IgG positive, EBNA-1 IgG positive, and EA-D IgG positive (or rising if you test again a few weeks later), especially if it lines up with your symptoms. If things are still unclear, a test that looks for the virus’s actual genetic material in your blood (called a PCR test) can help clear things up. This is a very different test than what most people get when their doctor says “we checked you for mono and you’re fine.”

What do you actually do with this information?

I want to be realistic here. There is currently no treatment that removes EBV from your body completely, once you’ve had it, it’s with you for life. So what does testing actually get you?

·      A real explanation for fatigue, brain fog, or muscle pain that’s been dismissed or blamed on other things

·      A reason to address things that may be fueling reactivation, treating unmanaged MCAS, correcting a low antibody level, cutting down on physical and emotional stress, and improving sleep and nutrition

·      In more severe cases, or if your immune system is significantly weakened, a conversation with an infectious disease or immunology specialist about antiviral medication, this isn’t something everyone needs, but it’s an option worth knowing about

·      Useful information for your medical team down the road if autoimmune symptoms show up later

The takeaway

If you have hEDS and you’re dealing with ongoing fatigue, brain fog, muscle pain, or early signs of an autoimmune condition, ask your doctor for a full EBV panel, not just the basic mono test. Given how often immune system problems show up alongside hEDS, this is a simple, low-risk test that’s worth adding to your workup, even while the research on EBV and hEDS specifically continues to catch up to what we already know about EBV’s role in MS, lupus, and immune dysfunction in general.

Stripe Strong 🦓

This article is for educational purposes and reflects a review of current research. It is not a substitute for individualized medical care. Talk to your physician about whether EBV testing is right for your specific situation.

If you’re a zebra reading this, chances are fibromyalgia may not be a stranger to you. Whether it’s your own diagnosis, a label a provider handed you along the way, or a condition that overlaps so heavily with your hypermobile EDS symptoms that the lines blur, fibromyalgia has probably been part of your story. This summer, a study came out that I think matters a great deal to this community, even though fibromyalgia and EDS are technically separate diagnoses.

The Study, in Plain English

At the end of July 2026, an international team of researchers published the largest genetic study of fibromyalgia ever conducted, in the journal Nature Medicine. It was led by Dr. Isabel Kerrebijn at the Lunenfeld-Tanenbaum Research Institute (Mount Sinai Hospital, Toronto), with collaborators including Fred Hutch Cancer Center and Dr. Daniel Clauw at the University of Michigan, a name recognized as one of the most prominent researchers in central sensitization and chronic pain.

The scale here is worth pausing on. Researchers analyzed genetic data from over 2.5 million adults, roughly 55,000 of whom had fibromyalgia. That kind of sample size is what allows a genetics study to find real, reproducible signals instead of noise.

What they found: 26 distinct regions of the genome associated with fibromyalgia risk, many of which involve genes tied to brain and nerve function. In other words, this adds substantial weight to something many of us in the pain and EDS world have believed for years, that fibromyalgia is not “in your head” in the dismissive sense some patients have been told, but is very much rooted in how the nervous system itself is built and regulated.

You can read the full paper here: https://www.nature.com/articles/s41591-026-04492-6

Why This Matters if You Have EDS

Fibromyalgia and hypermobile EDS overlap so often in clinical practice that it can be hard to tell where one ends and the other begins. Both involve widespread pain, fatigue, unrefreshing sleep, and cognitive fog. Both are conditions where patients have historically been dismissed, misdiagnosed, or told their symptoms were psychological. And a large share of my hEDS patients over the years have also carried a fibromyalgia diagnosis, commonly alongside a small fiber neuropathy (SFN) diagnosis.

That overlap is exactly why this study is relevant here, even though it wasn’t conducted in an EDS population specifically. A few reasons:

1. It reinforces that widespread pain in connective tissue disorders has a biological basis. For years, the chronic pain seen in hEDS patients has sometimes been minimized as “just” joint instability or “just” anxiety. This study adds to a growing body of evidence that central nervous system sensitization, the amplification of pain signals in the brain and spinal cord, is a real, identifiable, and now partially genetically mapped phenomenon. That matters when you’re sitting across from a provider who isn’t sure your pain is “real.”

2. It may help explain the fibromyalgia/SFN/hEDS triad. Many zebras with fibromyalgia also test positive for small fiber neuropathy on skin biopsy. This study’s finding that fibromyalgia risk genes cluster in brain and nerve pathways opens the door to future research asking whether there’s a shared genetic vulnerability connecting connective tissue laxity, small fiber damage, and central sensitization, rather than three unrelated problems that happen to occur together.

3. New drug pathways may cross over. One of the biological pathways implicated in this study is already being targeted in drug trials for Huntington’s disease. That’s a good example of how genetic discovery work in one condition can open unexpected doors in another. If a pathway is validated in fibromyalgia, it’s not a stretch to imagine that pathway being explored in EDS-associated pain and SFN down the road, since the mechanisms of nerve sensitization likely overlap.

4. It’s a step toward legitimacy and better research funding. Both fibromyalgia and EDS have suffered from a lack of biomarkers, which has made them easy to underfund and easy for skeptical providers to downplay. A genetic architecture this well-defined, in a sample this large, makes it much harder to argue fibromyalgia is a diagnosis of exclusion with no biological footing. That credibility often has ripple effects for adjacent, under-researched conditions like hEDS.

What This Doesn’t Mean (Yet)

It’s important to be honest about the limits here. This was a study of genetic risk factors, not a cure, not a new treatment, and not a diagnostic blood test you can ask your doctor for tomorrow. The study population was also primarily of European ancestry, which limits how well the findings generalize across all patients. And critically, this study was conducted in people diagnosed with fibromyalgia, it did not specifically study hEDS patients, so any connection to EDS or SFN is, for now, an inference based on clinical overlap rather than a proven genetic link.

The researchers have also founded a new collaborative effort, the Chronic Pain Genomics Consortium, to expand this kind of genetic mapping to other chronic pain conditions, starting with pelvic pain. My hope, and I’d guess many of yours too, is that hypermobile EDS and its associated pain syndromes eventually get this same level of large-scale genetic attention.

The Takeaway

If you live with hEDS and fibromyalgia, or hEDS and small fiber neuropathy, this study is a meaningful data point in a longer story: the growing recognition that the pain many zebras experience has identifiable, biological, nervous-system-based roots. It’s not the whole answer, but it’s a real step, from a very large and credible research team, toward taking this kind of pain seriously at the level of the genome.

Stripe Strong 🦓

This article is for educational purposes only and is not intended as medical advice. Please consult your own physician regarding your individual diagnosis and treatment.

If you have hypermobile Ehlers-Danlos Syndrome (hEDS), you already know the frustration of symptoms that overlap with a dozen other conditions. Joint pain. Fatigue. Skin changes. Raynaud’s-like color changes in your fingers. Brain fog. It’s easy, for you and sometimes for your doctors, to chalk everything up to “it’s just the EDS.”

But here’s the thing: EDS doesn’t make you immune to autoimmune disease. And because so many autoimmune connective tissue diseases (CTDs) - like lupus, Sjögren’s syndrome, rheumatoid arthritis, and mixed connective tissue disease - share symptoms with hEDS, they can hide in plain sight for years.

This is where a blood test called AVISE CTD enters the conversation.

What Is AVISE CTD?

AVISE CTD is a specialized blood panel made by a company called Exagen. It wasn’t designed for EDS, it was designed to help rheumatologists sort out whether a patient’s vague, overlapping symptoms (joint pain, fatigue, photosensitivity, dryness, Raynaud’s) are being caused by an autoimmune CTD like lupus, or something else entirely.

It does this by looking at a wider, more sensitive set of biomarkers than a standard ANA or rheumatoid factor test, including some proprietary markers (like cell-bound complement activation products) that aren’t part of routine bloodwork.

The Autoimmune Overlap Nobody Warned You About

This isn’t just theoretical. Studies consistently show hEDS patients have higher rates of autoimmune and inflammatory conditions - like lupus, rheumatoid arthritis, Sjögren’s, and autoimmune thyroiditis - than the general population, along with higher rates of ANA positivity and markers like HLA-B27. There’s no single agreed-upon number, but the pattern holds across labs, cohorts, and prescription data: this overlap is real, not coincidental.

Why This Matters for EDS Patients

Given how often autoimmune disease travels alongside hEDS, it makes sense that testing to catch it early matters. But here’s the important nuance: AVISE CTD is not a test for EDS. There is no blood test that diagnoses hEDS, it remains a clinical diagnosis based on physical findings and history. If someone offers you this test as a way to “confirm” your EDS, that’s not what it’s for.

Where it can be genuinely useful is in the gray zone many of you live in: when your symptoms don’t add up neatly to hEDS alone. For example:

• Joint pain that feels different, more inflammatory, or is accompanied by swelling rather than just instability

• New or unexplained fatigue that outpaces your usual baseline

• Photosensitivity, unexplained rashes, or dry eyes/mouth

• Raynaud’s phenomenon

• Abnormal labs your doctor already flagged, like a positive ANA

In these situations, distinguishing “this is my EDS” from “this is a second, treatable condition layered on top” isn’t just an academic exercise, it changes your treatment plan entirely. Autoimmune CTDs are treated with immune-modulating medications, not physical therapy and joint protection strategies. Missing one because it got absorbed into your EDS diagnosis can mean years of unnecessary organ risk and unmanaged disease.

The Bigger Picture: Why This Kind of Testing Deserves More Attention

Zebras are taught to expect complexity, but that same complexity can work against you. When a patient with hEDS shows up with new symptoms, there’s a real risk of diagnostic overshadowing, where every new complaint gets absorbed into the existing EDS diagnosis instead of being independently evaluated. Tests like AVISE CTD give clinicians a more sensitive way to look past that assumption when the clinical picture genuinely warrants it.

This doesn’t mean every hEDS patient needs this test. Ordering it reflexively on everyone with joint pain would be neither useful nor cost-effective. But for the subset of patients with atypical or evolving symptoms, the ones who keep saying “something else feels different”, it’s a reasonable tool to raise with your rheumatologist or physician.

The takeaway: being a zebra doesn’t rule out being a lupus patient, a Sjögren’s patient, or an RA patient too. If your symptoms are shifting or something feels genuinely different from your baseline EDS experience, that’s worth a conversation, and possibly a test, not an assumption.

By Jonathan Kost, MD

Stripe Strong 🦓

This article is for educational purposes and does not constitute individualized medical advice. Please discuss your specific symptoms and testing options with your physician.

For as long as I’ve been treating patients with hypermobile Ehlers-Danlos Syndrome (hEDS), we’ve operated under one core assumption: this is a genetic, structural problem. Your collagen is built differently from birth, and that’s why your joints move too far, your skin stretches too easily, and your body seems to fall apart in ways that mystify most doctors.

A new piece of research doesn’t overturn that assumption, but it does add a wrinkle worth talking about. And if you’re a zebra who’s ever wondered “why did my symptoms start after I got sick,” this one might resonate.

What the Researchers Found

A team studying Lyme disease, caused by the bacterium Borrelia burgdorferi (Bb), transmitted through tick bites, made two connected discoveries, one in mice and one in people.

In mice: When older female mice were infected with Bb long-term, researchers used special imaging to look inside their tissue. They found the bacteria actually living inside connective tissue, not just passing through, and saw visible signs of tissue damage under the microscope. This tells us Bb doesn’t just cause the joint pain and fatigue we associate with Lyme; it can take up residence in the very tissue that gives our bodies structure.

In people: The same team ran a clinical study, called MAESTRO, surveying people who’d had Lyme disease, been treated with antibiotics, and never fully recovered, a group sometimes referred to as having “chronic Lyme” or Post-Treatment Lyme Disease Syndrome. When they looked at these patients’ medical histories, they found a correlation between that unresolved, chronic illness and hypermobility disorders.

Why This Matters for the EDS Community

Here’s the sentence from the researchers that stands out: these findings “call into question a longstanding assumption that hypermobility disorders are in large-part benign and genetic.”

That’s a big statement. For decades, hypermobility has been treated as something you’re simply born with, a structural card you were dealt. This research suggests that, at least for some people, chronic infection might be a trigger or contributor to hypermobility symptoms showing up or worsening, not just a coincidence layered on top of genetics.

Put simply: it may not always be “either genetics or infection.” For some patients, it could be genetics and infection, the infection acting as the spark that reveals or worsens an underlying vulnerability that was already there.

A Theory Worth Sitting With: It’s Not Just the Structure, It’s the System

This lines up with something many of us in the EDS/POTS/MCAS world have been circling for years: that connective tissue fragility might not always be a purely structural, mechanical defect. It could also be a downstream consequence of ongoing inflammation - nerves, mast cells, and the tissue’s protective barriers getting worn down over time by something the body is fighting, like a chronic infection.

If that’s true, it reframes hypermobility symptoms less as “broken scaffolding” and more as “scaffolding under sustained attack.” That distinction matters enormously for how we think about treatment, because you can’t fix an infection-driven or inflammation-driven problem the same way you’d approach a purely structural one.

What This Does Not Mean

To be clear about the limits here:

·      This does not mean Lyme disease causes hEDS. hEDS has a strong hereditary and connective-tissue basis that this research doesn’t erase.

·      This is early-stage research, a mouse model plus a correlational clinical survey. Correlation in a patient history survey is a signal to investigate further, not proof of cause and effect.

·      Most people with hEDS have never had Lyme disease, and most people who’ve had Lyme disease don’t develop hEDS.

Why It’s Still Worth Paying Attention To

What this research does offer is a genuinely new angle on an old question many zebras ask: “Why did things get so much worse after that illness?” or “Why did my joints and skin change after I got sick?” For patients who trace their symptom onset to an infection, Lyme or otherwise, this is the first real scientific thread suggesting that connective tissue and chronic infection may be more intertwined than we’ve given them credit for.

It also strengthens the case for something many of us already believe clinically: that hEDS care shouldn’t stop at joints and collagen. The nervous system, the immune system, and mast cells all appear to be part of the same tangled web, and untangling it may require looking well beyond genetics alone.

We’ll be watching for the full published data as this research matures. For now, consider this one more piece of evidence that our bodies’ “why” is rarely simple and that curiosity, not certainty, is still our best tool as a community.

Stripe Strong 🦓

As always, this article is for educational purposes and is not a substitute for individualized medical advice from your own care team.

Jonathan Kost, MD

A new skin-biopsy study out of Naples gives us the clearest evidence yet that the burning, numbness, dizziness, and gut chaos so many of you live with isn’t “just anxiety”, it’s measurable nerve pathology, and it looks different in hEDS than it does anywhere else.

If you’ve spent any time in the EDS/POTS/MCAS corner of the internet, you already know the frustration: you describe generalized pains, skin sensitivity to touch, temperature regulation issues, abnormal sweating, a racing heart when you stand up, GI symptoms that make no sense, and a bladder that never got the memo, and somewhere along the line, a provider decides this is all “in your head” or, at best, files it under a vague label like small fiber neuropathy (SFN) and moves on.

A study just published in Scientific Reports (Dell’Aversana, Provitera, Nolano, and colleagues, July 2026) says: not so fast. This isn’t generic Small Fiber Neuropathy (SFN). It’s a distinct disease pattern and now we have the biopsies to prove it.

What they actually did

The team, out of the University of Naples Federico II and the Skin Biopsy Lab in Telese Terme, did something that’s surprisingly rare in this field: they directly compared two groups of patients with small fiber neuropathy:

·      35 patients who had SFN and met the 2017 diagnostic criteria for hypermobile EDS

·      38 age-matched patients with SFN but no EDS (idiopathic SFN, or iSFN)

Both groups went through the same rigorous workup: validated symptom questionnaires (SFN-SIQ, DN4, COMPASS-31), quantitative sensory testing, autonomic testing (heart rate/blood pressure reflexes, sweat testing), and skin biopsies from three different sites (leg, thigh, and fingertip) to actually count nerve fiber density under the microscope.

What they found

Four things jumped out, and if you have hEDS, none of them will surprise you but now they’re in a peer-reviewed paper with numbers attached.

1. Symptoms start young, really young.

The hEDS/SFN group had a mean age of symptom onset of 19.5 years, compared to 35.2 years in the idiopathic SFN group. That’s not a small gap. This tracks with what so many of you have told me for years: the aching or burning pains, the fatigue, the “growing pains” that never went away, they didn’t start in your 40s or 50s like classic SFN. They started when you were a teenager, and everyone told you it was normal.

2. The pain is everywhere, not just your feet.

Classic idiopathic (unknown cause) SFN tends to follow a “stocking-glove” pattern, commonly starts in the feet, creeps up. hEDS-related SFN was more generalized throughout the body pain (Fibromyalgia-like) and diffuse from the start. This matches the whole-body, unpredictable nature of the pain so many of you describe, which doesn’t fit neatly into the textbook neuropathy pattern your neurologist was trained to look for.

3. Autonomic symptoms were dramatically worse - and POTS was everywhere.

Small fiber neuropathy doesn’t just affect the nerves that carry pain and temperature signals, it also damages the thin, unmyelinated autonomic fibers that control blood vessel tone, heart rate regulation, sweating, and gut and bladder function. When those fibers are lost or malfunctioning, the body loses its ability to properly constrict blood vessels and adjust heart rate when you stand up, which is a core mechanism behind orthostatic intolerance and POTS and the same fiber damage disrupts the nerves governing digestion and bladder control, which is why GI and urinary symptoms so often travel together with the dizziness and racing heart. Using the COMPASS-31 autonomic symptom score, the hEDS/SFN group scored 54.3 versus 33.9 in the iSFN group, driven especially by orthostatic intolerance, GI symptoms, and bladder symptoms. And here’s the number that should end a lot of arguments in exam rooms: 51.5% of the hEDS/SFN group had POTS. Zero percent of the idiopathic SFN group did. POTS isn’t a coincidental add-on in hEDS, it’s part of the same underlying process.4. The nerve damage itself is different under the microscope.

Both groups showed similar loss of the small sensory nerve fibers in the skin, so if you only looked at sensory fibers, you might conclude “it’s all the same disease.” But when the researchers looked specifically at the autonomic nerve fibers, the ones that control blood vessels, sweat glands, and organ function, the hEDS group had significantly greater loss. This is the piece that’s been missing: objective, structural evidence that the autonomic nervous system itself is more damaged in hEDS than in run-of-the-mill SFN.

Why this matters for you

I’ve spent over a decade in clinics watching hEDS patients get bounced between specialists, each one only willing to evaluate their own organ system, none of them connecting the dots. This study is a big deal because it does three things at once:

·      It validates that hEDS-related small fiber disease is its own entity, not a “variant” or a coincidence layered on top of joint hypermobility. The onset age, the distribution, the autonomic severity, and now the biopsy findings all point the same direction.

·      It gives autonomic symptoms equal billing with pain. For years, the conversation around hEDS and nerves has centered on pain. This paper says the autonomic nervous system damage may actually be the more distinctive and more measurable feature.

·      It builds the case for systematic autonomic testing as standard of care in hEDS, not something you have to fight for after your tenth ER visit for a racing heart. The authors say this explicitly: routine autonomic assessment and targeted management should be considered in this population.

What to do with this

If you have hEDS and you’ve been told your dizziness, GI symptoms, or burning pain are “just anxiety” or unrelated to your connective tissue disorder, this paper is worth bringing to your next appointment. So you (and your doctor) can read the whole thing.

https://www.nature.com/articles/s41598-026-60461-6

This won’t be the study that changes everything overnight. But it’s exactly the kind of hard, boring, meticulous, multi-site skin-biopsy work that turns “the zebras’ anecdotes” into “the medical literature.” That’s how standards of care get built, one careful comparison group at a time.

Stay strong, zebras!! The data is finally starting to catch up to what you’ve been telling us all along. Better diagnostics and treatments are on the horizon!!

Dr. Jonathan Kost is a board-certified anesthesiologist and interventional pain medicine specialist, founder of the Connecticut Pain Society, medical director and owner of Connecticut’s only EDS-internationally certified pain management center.and author of The Hypermobile EDS Survival Handbook.

Medical Disclaimer: This article is for informational and educational purposes only and does not constitute medical advice. It is not a substitute for professional medical evaluation, diagnosis, or treatment. Always consult your physician or a qualified healthcare provider regarding any medical condition, including hypermobile EDS or related hypermobility disorders, especially in children.

If you have hypermobile Ehlers-Danlos Syndrome (hEDS), you already know that your joints don’t just move more than they should, they often move without you knowing it moved. That’s not a minor detail. It’s the whole problem. And it’s exactly why kinesiology taping has become one of the tools that may help.

The Real Issue Isn’t Just Laxity - It’s Proprioception

Most people think of hEDS purely in terms of stretchy skin and joints that bend the “wrong way.” But part of the problem that actually drives day-to-day disability, the knee that buckles on stairs, the shoulder that subluxates reaching for a cabinet, the neck that feels like it’s going to give out, the SI joint that locks up for no obvious reason, comes down to proprioception: your joint’s built-in sense of where it is in space.

In a normal joint, ligaments, tendons, and skin all feed constant position and movement data back to the central nervous system. In hEDS, that connective tissue is looser and doesn’t transmit that signal as efficiently. The joint is unstable and the brain doesn’t get accurate, timely information about that instability until something has already gone wrong. That combination, mechanical laxity plus a degraded feedback loop, is why patients with hEDS report such a wide range of joint-specific problems: patellofemoral (kneecap) pain and instability, recurrent shoulder subluxation, cervical instability, SI joint dysfunction, and generalized multi-joint pain.

Kinesiology tape doesn’t add rigid, mechanical support the way a brace does. What it does, is provide continuous, low-level cutaneous stimulation across the skin overlying the joint. That stimulation feeds the nervous system additional sensory input, essentially turning up the volume on a signal that’s normally too quiet in hEDS. Patients frequently described becoming more aware of the joint, before it moved too far, not after.

What I Observed Across Different Joints

Shoulders. This is where I saw kinesiology taping make a consistent difference, and it’s also the area with the best supporting data (more on that below). Patients with recurrent subluxation often described feeling more “contained” in the joint and more confident reaching overhead or behind their back, tasks that otherwise provoked a guarding response.

Knees / patellofemoral joint. For patients dealing with patellar (kneecap) tracking issues (an extremely common issue with hEDS) or a knee that felt like it would give way descending stairs, taping tends to improve patellar tracking alignment and confidence and reduce the guarded, stiff gait pattern that so many hEDS patients develop as a protective habit. Less guarding, in turn, tended to reduce the secondary muscle tension and pain that guarding itself creates.

Cervical spine. This is a more delicate area, and I was always conservative with it, but light taping around the cervical paraspinals and upper trapezius appeared to help some patients with mild-to-moderate cervical instability feel more supported during activities of daily living. This was never a substitute for proper cervical stability training or medical workup, it’s an adjunct.

SI joint. Sacroiliac dysfunction is common in hEDS and often very under-recognized. Taping across the SI joint and gluteal region appeared to help some patients modulate pain during transitional movements like standing from sitting, or rolling in bed.

Elsewhere - wrists, thumbs, ankles - the same logic applies: give the nervous system more information, reduce unconscious over-movement, and reduce the compensatory muscle guarding that so often becomes its own pain generator.

None of this means taping “fixes” instability. It doesn’t replace targeted strengthening, joint-protection strategies, or, in some cases, bracing or surgical consultation. But as an adjunct that costs very little and carries low risk, it earned its place in a comprehensive hEDS management plan in my experience.

Application Technique Matters — A Lot

I want to be direct about this: poorly applied kinesiology tape will do absolutely nothing, or can actively cause skin irritation, blistering, or a false sense of security that leads to overuse of an unstable joint. The tension of the tape, the direction of pull, the anchoring at each end, and the position of the joint during application all matter. A few key principles:

·      The tape should be applied with the joint in proper alignment, not in a stretched or already-compromised position.

·      The anchor ends (the first and last inch of tape) should be applied with little to no stretch, most irritation happens at these ends.

·      Stretch through the middle of the tape strip is typically light to moderate (roughly 25–50%), not maximal.

·      Skin should be clean, dry, and free of lotion before application, and the tape should be rubbed to activate the adhesive.

·      Because many hEDS patients also deal with skin fragility, allergies, or mast cell activation, a patch test with a small strip is worth doing before a full application, and hypoallergenic tape options exist for sensitive skin. If skin irritation develops from the tape, one could try a skin barrier solution, such as Cavilon. Skin irritation issues seem to be the main obstacle as to why hEDS individuals decide not to utilize kinesiology taping.

·      Wear time is typically capped around three days, less if there’s any sign of irritation.

If you’re new to taping, don’t guess. Get proper instruction, ideally from a physical therapist, occupational therapist, or athletic trainer who has specific experience with hypermobility, not just general sports taping.

Where to Learn Proper Technique

For patients who want to learn self-application (or want to see what proper technique looks like before their next PT visit), here are some genuinely useful places to start on YouTube:

·      The Fibro Guy - this channel focuses specifically on taping for fibromyalgia and hypermobility conditions, including EDS. They have dedicated videos on taping the knee, thoracic spine, wrist/forearm, and thumb specifically for hypermobile patients, which is more targeted than most general taping content out there.

·      RockTape’s official YouTube channel - a large library of instructional taping videos across nearly every joint. RockTape is one of the more clinically-oriented tape brands and is frequently used by physical therapists, so their technique videos tend to be solid and consistent.

·      KT Tape’s official video tutorials (available on their site and YouTube) - another well-established brand with a large tutorial library covering joint-specific applications.

·      Search for “K-taping for shoulder subluxation EDS” or similar hEDS-specific search terms, there are physical therapists who specialize in EDS/hypermobility who post joint-specific tutorials aimed directly at this population rather than general athletic taping, which tends to translate better to hEDS patients’ actual needs.

A word of caution with YouTube: technique quality varies a lot, and a video made for an athlete’s ankle sprain is not automatically appropriate for a hypermobile joint. Use these resources to supplement, not replace, instruction from a clinician who has actually assessed your specific joint instability pattern.

Bottom Line

Based on more than a decade treating patients with EDS, kinesiology taping struck me as a low-risk, low-cost tool that can meaningfully improve proprioceptive feedback and functional confidence across the shoulder, knee, cervical spine, SI joint and other joints. It works best as one piece of a broader plan - strengthening, joint protection, activity modification, and, when appropriate, bracing - rather than a stand-alone fix. If you haven’t tried it, it’s worth a conversation with your current physical therapist or physiatrist about whether it fits into your plan of care.

Also, talk to your treating clinician before starting or changing any taping regimen, especially if you have skin fragility, mast cell activation syndrome, or a history of adverse reactions to adhesives.

Jonathan Kost, MD is a board-certified anesthesiologist and interventional pain medicine specialist, founder of the Connecticut Pain Society, medical director and owner of Connecticut’s only EDS-internationally certified pain management center.and author of The Hypermobile EDS Survival Handbook.

Medical Disclaimer: This article is for informational and educational purposes only and does not constitute medical advice. It is not a substitute for professional medical evaluation, diagnosis, or treatment. Always consult your physician or a qualified healthcare provider regarding any medical condition, including hypermobile EDS or related hypermobility disorders, especially in children.

If you have hypermobile EDS, you’ve probably noticed you’re not just dealing with joints that move too much. You’re also more likely than the average person to be dealing with Hashimoto’s thyroiditis, mast cell activation syndrome (MCAS), unexplained rashes, gut problems that look autoimmune, or nerve symptoms nobody can quite pin down. This isn’t in your head, and it isn’t a coincidence. Research backs it up: one study found the odds of having MCAS if you have hEDS are over five times higher than you’d expect by chance. Another found nearly two out of three hEDS patients met the criteria for MCAS.

What’s been missing is an answer to the obvious question: why? Why would a connective tissue disorder make you more prone to autoimmune disease at all? Here’s a working theory, built from real pieces of research that, as far as we can tell, nobody has put together into one story specifically for EDS before.

The Theory, in Plain Terms

Your collagen problem may be setting off a chain reaction: it primes your mast cells to be on a hair trigger, that constant low-grade inflammation wears down your immune system’s ability to keep old viruses like Epstein-Barr in check, and every time those viruses reactivate, your body gets another chance to make an antibody mistake, one that ends up attacking your own thyroid, joints, or nerves instead of the virus.

Think of it like a smoke detector with a chewed-up wire. It’s already twitchy, going off over things that shouldn’t set it off. Now put a small, ordinary fire nearby, something your body deals with all the time without issue, and instead of a controlled response, the whole system overreacts and starts causing damage of its own.

Let’s walk through it step by step. Each piece below is backed by real research. What’s new is connecting them.

Step 1: Bad collagen puts mast cells on edge

Mast cells are immune cells that live in your connective tissue and release chemicals, histamine and others, when they sense a threat. In hEDS, the collagen scaffolding they sit in is built differently, and there’s growing evidence this abnormal scaffolding itself makes mast cells more reactive. That’s a real, documented reason MCAS shows up in hEDS patients so much more than in the general population. Genetic studies have even found overlapping gene variants, including some tied to immune regulation, shared between hEDS and mast cell problems.

Step 2: Trigger-happy mast cells create constant low-grade inflammation

Once your mast cells are primed like this, they don’t just fire off in one spot. Their chemical messengers circulate through your body. That’s a big part of why hEDS comes with such a wide, frustrating list of symptoms - fatigue, GI issues, nerve pain, dizziness on standing - that don’t fit neatly into one diagnosis. Your whole system is running a low simmer of inflammation, all the time.

Step 3: That constant inflammation wears down your body’s ability to keep old viruses asleep

Here’s where it gets interesting. Over 90% of adults have been infected with Epstein-Barr virus (EBV), the virus behind mono, at some point, usually without realizing it. After that first infection, EBV doesn’t leave. It goes dormant in your immune cells and, in a healthy immune system, mostly stays that way. But your immune system has to keep actively suppressing it, day after day, using specific cells whose whole job is watching for that virus trying to wake back up.

In other autoimmune diseases like lupus, researchers have found something specific: patients’ virus-watching immune cells become worn out and less effective, letting EBV reactivate more often. If hEDS keeps your immune system running hot for structural reasons, not autoimmune reasons, it’s reasonable to think the same kind of wear-and-tear on your virus surveillance could be happening, even before any autoimmune disease shows up.

Step 4: Every time the virus wakes up, your body gets another chance to make a mistake

When EBV reactivates, your immune system builds new antibodies to fight it. The problem is, some proteins on the virus happen to look a lot like proteins in your own body - your thyroid, your joints, your nerves. This is called molecular mimicry, and it’s a well-established mechanism behind conditions like multiple sclerosis. The more times EBV reactivates over the years, the more “rolls of the dice” your body gets, more chances for one of those antibodies to misfire and start attacking your own tissue instead. If you also happen to carry certain genetic variants that make you more autoimmune-prone (which research suggests overlaps with the same genes involved in hEDS mast cell issues), the odds of one of those misfires actually taking hold and becoming a real disease go up further.

Step 5: Once autoimmune disease sets in, it gets harder to fix

This is the frustrating part. In lupus and Sjögren’s, once autoimmune disease is established, patients’ ability to control EBV reactivation stays impaired, even during periods when the disease itself is quiet. It may also be harder to get the underlying viral reactivation back under control once the autoimmune disease is already there, because the disease itself keeps disabling the very immune function that would normally suppress the virus.

Why This Matters Even Though It’s Not Proven Yet

To be completely honest, no one has run the exact study that proves this whole chain, start to finish, in EDS patients specifically. Every individual step above has real research behind it in other contexts. Stitching them together into “this is what’s happening in zebras” is an educated, testable theory, not an established fact. That distinction matters, and it’s exactly why this deserves real research, not just a confident claim.

That said, a good theory should point somewhere useful. Here’s what it suggests, in terms of what’s worth exploring with your doctor:

What This Might Mean for Treatment

Calm the mast cells first. This part isn’t hypothetical, controlling mast cell activity is already well-supported on its own, regardless of the virus theory. Antihistamines (both H1 and H2 blockers), mast cell stabilizers like Cromolyn and Quercetin, identifying your personal trigger foods, and in some cases other targeted medications can lower that baseline inflammatory simmer.

Ask about checking for chronic viral reactivation. If you have hEDS and you’re dealing with new or worsening symptoms that look autoimmune, it’s reasonable to ask whether your doctor will run a full EBV panel, not just a quick mono test, but the fuller antibody panel that shows whether the virus has been reactivating in the background. Most conventional workups don’t include this by default, so you may need to specifically ask.

Don’t expect antiviral pills to be a magic fix. Common antivirals don’t work well against EBV once it’s gone dormant, which is the stage that matters most here. If a treatment plan leans entirely on “just take an antiviral,” that’s a red flag that the plan isn’t grounded in how this virus actually behaves.

Support your immune system’s ability to do its job. This might look like correcting a vitamin D deficiency (common in hEDS and known to support immune function), addressing HPA axis / stress-hormone imbalances that can suppress your immune response, and generally working on the whole-body inflammation picture rather than chasing one symptom at a time.

The bigger picture, treating the source, not just the symptoms. If the root of all this really is the collagen environment itself keeping your mast cells on edge, then anything that genuinely supports connective tissue health, this is still early and speculative territory, including newer regenerative approaches, could theoretically calm the whole cascade from its starting point, rather than just managing what it produces further downstream.

The Bottom Line

You are not imagining the connection between your EDS and your autoimmune symptoms. There’s a real, plausible chain of events that could explain why zebras get hit with autoimmune disease so much more often, starting with collagen, running through mast cells, and ending with a virus almost everyone carries getting more chances than it should to cause real damage. It hasn’t been proven end-to-end yet. But it’s a theory worth researching, and worth bringing up with your care team, because right now, almost nobody is looking at the whole possible chain of events.

Dr. Jonathan Kost is a board-certified anesthesiologist and interventional pain medicine specialist, founder of the Connecticut Pain Society, medical director and owner of Connecticut’s only EDS-internationally certified pain management center.and author of The Hypermobile EDS Survival Handbook.

Medical Disclaimer: This article is for informational and educational purposes only and does not constitute medical advice. It is not a substitute for professional medical evaluation, diagnosis, or treatment. Always consult your physician or a qualified healthcare provider regarding any medical condition, including hypermobile EDS or related hypermobility disorders, especially in children.

If you have hypermobile Ehlers-Danlos Syndrome (hEDS), you’ve probably had this experience: you tell a doctor about your joint pain, and they nod. You mention the dizziness, and they nod again. Then you get to the fatigue, the kind that doesn’t lift with sleep, that makes a shower feel like a workout, and something shifts. The nodding slows down. This is where symptoms start to feel disconnected from a “connective tissue disorder,” and where patients are often quietly handed a referral to psychiatry instead of an answer.

For years, there hasn’t been a great scientific explanation for why hEDS produces this sprawling list of symptoms - fatigue, gut dysmotility, brain fog, migraines, bone fragility - that seem to have little to do with stretchy skin or loose joints. Emerging research is now pointing to a possible unifying thread: mitochondrial dysfunction.

This isn’t a cure, and it isn’t proof. But it’s a real and rapidly developing area of science, and it’s worth understanding.

Why hEDS Has Always Been a Genetic Mystery

Every other type of Ehlers-Danlos Syndrome has a known genetic cause, a specific collagen gene, a specific mutation. hEDS is the outlier. It’s also the most common form of EDS, affecting an estimated 3% of the population by some recent estimates, yet it remains the only major EDS subtype with no identified causative gene. Diagnosis still relies entirely on clinical criteria, hypermobility scores, skin findings, family history, because there’s no blood test that can confirm it.

That gap matters. It’s a big part of why so many hEDS patients spend a decade or more collecting misdiagnoses (anxiety, fibromyalgia, “it’s all in your head”) before someone recognizes the pattern.

The Mitochondrial Hypothesis

A team at Boston University’s EDS Clinical Research Program, led by Michael Holick, has been building a case that mitochondria, the energy-producing structures in every cell, may be a missing piece of this puzzle.

Their reasoning starts with basic cell biology: making collagen is energy-expensive. Mitochondria supply the ATP needed for collagen synthesis, the post-translational modifications that stabilize collagen’s structure, and the tissue repair process itself. If mitochondrial energy production is impaired, the theory goes, connective tissue would be one of the first things to suffer, but so would every other high-energy-demand system in the body: muscles, the gut’s smooth muscle and nerve networks, and the brain.

That would help explain a lot at once: why hEDS symptoms extend so far past joints and skin, why fatigue is so central and so disabling, and why no single collagen gene has ever explained the majority of cases.

In a 2025 scoping review, the Boston University team synthesized the (admittedly sparse) existing literature, just eight original studies met their inclusion criteria, and found early but real signals: impaired oxidative energy production in hEDS patients’ skin cells, elevated markers of oxidative stress, and even individual case reports of patients carrying mutations in mitochondrial DNA genes involved in energy production.

From Theory to Data

Here’s the part that makes this more than speculation: the same group followed up with an actual genetic study, not just a literature review. Published in early 2026, it sequenced the exomes of 116 people from 43 families, 86 with hEDS, 30 unaffected relatives as controls, specifically checking all 37 mitochondrial genes alongside the rest of the genome.

The result: variants in mitochondrial respiratory-chain genes showed up in about a third of hEDS patients, compared to roughly 7% of unaffected relatives. The signal was even stronger in a specific subgroup, children with hEDS who had experienced fractures showed four times the rate of these mitochondrial variants compared to hEDS patients without fractures.

To be fair to the science, mitochondrial variation wasn’t the biggest signal in the study, collagen gene variants and immune-related HLA gene variants were both more prevalent. And the researchers themselves are unusually careful to say that finding a genetic variant is not the same as proving it causes a functional problem. They call their own findings “hypothesis-generating” and are explicit that this needs to be replicated in other, unrelated patient populations before anyone draws firm conclusions.

Why This Matters - and Why We Need More Research

This is exactly the kind of moment where patient advocacy and research funding intersect. Mitochondrial disease as a whole has historically been underfunded relative to how many people it affects, in part because it doesn’t map neatly onto a single organ system or a single specialty. That’s beginning to change. Organizations like Countdown, a nonprofit built specifically around accelerating mitochondrial science, have made the case that cellular energy dysfunction is a shared root cause running underneath a surprising range of conditions, rare diseases, neurodegeneration, chronic illness, aging, and that funding the underlying biology, rather than chasing each downstream diagnosis separately, is the faster path to real treatments. Their work funding mitochondrial repair and quality-control research is a good example of the kind of basic science that a condition like hEDS may eventually benefit from, even though it wasn’t designed with EDS specifically in mind.

That’s the point, really. hEDS research doesn’t need to reinvent mitochondrial science from scratch, it needs a seat at a table that’s already growing. But someone has to make the connection, fund the EDS-specific studies, and push for hEDS patients to be included in mitochondrial research the same way patients with Parkinson’s or muscular dystrophy already are.

What This Means for You Right Now

Nothing here should change what you’re doing today. There’s no approved mitochondrial treatment for hEDS, and there won’t be one until this research is replicated in independent patient groups and tested in actual clinical trials. If your doctor is discussing supplements like CoQ10, red light therapy, or lifestyle strategies around energy pacing, that’s a reasonable conversation to have, but it’s support for symptoms we already know about, not a mitochondrial “fix” backed by trial data.

What this research does offer is something patients have been asking for all along: a plausible biological explanation for why hEDS feels the way it does, beyond “your joints are loose.” That validation matters. And it opens a door, a narrow one, for now, toward research that could eventually change how hEDS is diagnosed and treated.

The mitochondria didn’t get us into this mess alone, and they probably won’t get us out of it alone either. But for the first time, we have a thread worth pulling.

 Dr. Jonathan Kost is a board-certified anesthesiologist and interventional pain medicine specialist, founder of the Connecticut Pain Society, medical director and owner of Connecticut’s only EDS-internationally certified pain management center.and author of The Hypermobile EDS Survival Handbook.

Medical Disclaimer: This article is for informational and educational purposes only and does not constitute medical advice. It is not a substitute for professional medical evaluation, diagnosis, or treatment. Always consult your physician or a qualified healthcare provider regarding any medical condition, including hypermobile EDS or related hypermobility disorders, especially in children.

Two complex conditions, one urgent need: Dedicated research into the connection between hEDS and autoimmune disease.

If you have hypermobile Ehlers-Danlos Syndrome (hEDS), you’ve probably noticed something in your own life or in the EDS community: autoimmune conditions seem to show up more than they “should.” Hashimoto’s thyroiditis. Celiac disease. Lupus. Sjögren’s. It’s common enough in clinical conversation that it almost feels assumed. But how much of this is actually measured, and how much is pattern-matching from shared experience? The honest answer is: a little of both, and the gap between the two is exactly where more research needs to happen.

What’s Actually Been Measured

Two links have real numbers behind them.

The strongest is celiac disease. A large US database study (using the All of Us research program) found that people with EDS had roughly a 9-fold increase in odds of also having celiac disease, compared to the general population. This held up even after researchers controlled for other autoimmune conditions and addressed concerns that doctors might just be looking harder for celiac in EDS patients (a bias that had muddied some earlier European studies).

The second is multiple sclerosis. A 2008 UK study found EDS was 10 to 11 times more common among MS patients than expected. That’s a striking number, but it comes from just four comorbid cases out of 1,892 patients at a single MS clinic. It’s a signal worth taking seriously, not a settled fact.

What’s Observed Clinically, But Not Yet Quantified

Beyond those two, a consistent cluster keeps appearing in case reports and clinical literature, without the kind of large-scale odds-ratio data that would let anyone put a solid number on it:

         •       Hashimoto’s thyroiditis

         •       Sjögren’s syndrome

         •       Systemic lupus erythematosus

         •       Rheumatoid arthritis

These conditions are frequently mentioned alongside EDS, POTS, and mast cell activation syndrome in clinical writing. But “frequently mentioned” and “rigorously measured” are different things, meaning doctors and researchers have noticed the pattern often enough to write about it, but no one has yet done the large, systematic study that would tell us exactly how common it really is, or rule out other explanations. And right now, most of this cluster lives in that first category: real clinical observation, still waiting on the data to back it up.

A Clinician’s Perspective

I’ll add my own observation here, for whatever it’s worth alongside the data above: after more than a decade of treating EDS patients, my strong clinical impression has consistently been that autoimmune conditions run higher in this population than the current literature has fully captured. That’s not a substitute for a large, well-designed study, it’s exactly why one is needed. When experienced clinicians across the EDS field keep noticing the same pattern independently, that’s usually a sign the research hasn’t caught up to the clinical reality yet, not that the pattern isn’t real.

An Important Distinction

hEDS itself is not an autoimmune disease. It’s a connective tissue disorder rooted in collagen and structural protein differences. The working hypothesis isn’t that EDS is autoimmune, it’s that something about having EDS may create conditions where autoimmune disease is more likely to take hold. Proposed mechanisms include chronic immune activation, increased intestinal permeability, and genetic overlap in immune-regulating genes, but these remain theories, not demonstrated causes.

Where Research Needs to Go  and Why the EDS Community’s Voice Matters

The honest state of the field: we have two well-measured associations, one much larger cluster of clinical suspicion, and almost no research connecting the dots between them. Large-scale, prospective studies, ones that track hEDS patients over time rather than counting existing cases in a single clinic, could tell us whether the Hashimoto’s/Sjögren’s/lupus/RA pattern is real at the population level or an artifact of a chronically ill population getting more medical attention.

This is exactly why continued advocacy from the EDS community matters. Rare and underdiagnosed conditions don’t get research funding by accident, they get it because patients, clinicians, and organizations keep pushing for recognition until the medical establishment listens. Every zebra who asks their doctor a pointed question, every patient who joins a registry or study, and every clinician who documents these patterns is part of building the evidence base that doesn’t yet exist.

What This Means for You, Your Family and Loved Ones

None of this is a reason for alarm. It’s a reason for awareness. If you have hEDS, this is worth a conversation with your practitioner, not because you should expect to develop an autoimmune condition, but because knowing your own risk profile means catching things earlier if they do appear. Reasonable questions to bring to your next appointment might include whether baseline thyroid or celiac screening makes sense for you, and what symptoms would warrant closer follow-up.

The bigger picture: two real numbers, one strong clinical pattern (including from where I sit, after years in clinic), and a research gap wide enough to justify continuing to push, loudly and persistently,  for the studies that will eventually close it.

Dr. Jonathan Kost is a board-certified anesthesiologist and interventional pain medicine specialist, founder of the Connecticut Pain Society, medical director and owner of Connecticut’s only EDS-internationally certified pain management center.and author of The Hypermobile EDS Survival Handbook.

Medical Disclaimer: This article is for informational and educational purposes only and does not constitute medical advice. It is not a substitute for professional medical evaluation, diagnosis, or treatment. Always consult your physician or a qualified healthcare provider regarding any medical condition, including hypermobile EDS or related hypermobility disorders.

Stripe Strong 🦓🦓🦓

I want to be upfront: this is early-stage research. Some of what follows comes from small human trials in other conditions, some from animal studies, and some is still in the preclinical or Phase 1 stage. None of it is an approved, EDS-specific treatment yet. But the biological logic behind several of these peptides lines up closely with what we already know is going wrong in hypermobile EDS, small fiber nerve damage, chronic inflammation, and connective tissue that just doesn’t repair the way it should. That overlap is why I think it’s worth understanding, even while we wait for better evidence.

My goal is to keep Zebras informed and educated to the evolving climate in medicine that potentially could help this community. These articles are here to empower you to become your own strongest advocate. The more you understand your condition, the more control you gain over your health. In many cases, being well-informed, sometimes even more up to date than your clinician on current research and emerging treatments, can help drive better conversations, improve your care, and ultimately push the medical community to place greater focus on EDS.

ARA290 (Cibinetide): A Peptide for Small Fiber Nerve Pain

One of the most established players in this space is ARA290, also known as cibinetide. It’s a small peptide built from a piece of erythropoietin’s structure, engineered so it calms inflammation and helps repair nerves without affecting red blood cell production.

Its best evidence so far comes from small fiber neuropathy caused by sarcoidosis and diabetes. In placebo-controlled trials, patients receiving cibinetide saw measurable regrowth of small nerve fibers in the cornea, along with real improvements in pain and daily function, with a good safety record.

Why does this matter for us? Small fiber neuropathy is increasingly recognized in hypermobile EDS. Research out of Lausanne found objective evidence of small fiber dysfunction in the majority of hEDS/HSD patients tested, the same burning pain, numbness, and autonomic symptoms so many zebras describe. There’s no completed hEDS-specific trial of cibinetide yet, but the mechanistic overlap is exactly why researchers and patients keep circling back to it.

A New Peptide for Endometriosis

For the many zebras who also live with endometriosis, there’s genuinely fresh news. In March 2026, a biotech called EndoCyclic Therapeutics received FDA clearance to begin human trials of ENDO-205, described as the first peptide therapy designed not just to manage endometriosis pain, but to target and reduce the lesions themselves, without relying on hormonal suppression.

This is very early: Phase 1 hasn’t even started dosing patients yet, and everything so far is preclinical. But it’s a meaningful shift, because current endometriosis treatment is almost entirely hormonal and symptomatic. A non-hormonal option that addresses the underlying tissue would be a big deal for the many EDS patients whose endometriosis and pelvic pain compound their connective tissue symptoms.

The Regenerative Peptides Everyone’s Talking About: BPC-157, TB-500, GHK-Cu, and KPV

These four show up constantly in EDS peptide forums, and each has a plausible story:

·      BPC-157, originally studied as a gastric-protective compound, has shown striking tendon, ligament, and muscle-to-bone healing in rodent studies, along with a strong safety margin in that same research.

·      TB-500, a fragment related to thymosin beta-4, is often paired with BPC-157 for its role in cell migration and tissue repair.

·      GHK-Cu, a copper-binding peptide, has decent evidence for boosting collagen and connective tissue matrix production in skin and cartilage cells.

·      KPV, a small fragment of a natural anti-inflammatory hormone, is of particular interest for the gut and mast cell issues so many of you carry alongside our joints, MCAS, IBS-type symptoms, and the like.

Here’s the honest caveat: none of these four have been studied in human EDS trials. The evidence is animal research, mechanistic plausibility, and patient-reported experience, which matters, but isn’t the same as proof. Sourcing is also a real concern, since most of what’s available comes from compounding pharmacies rather than FDA-approved channels, which means quality and purity can vary significantly.

What This Means for You

I’m not writing this to tell you to run out and start peptide therapy tomorrow. I’m writing it because our community deserves to know what’s actually being researched, and what’s still just promising, rather than proven. If you’re curious about any of these, the right first step is always a conversation with a physician who understands both EDS and peptide pharmacology, not a compounding pharmacy website.

What excites me isn’t any single peptide, it’s the direction. For the first time, research is starting to target the actual biology of connective tissue fragility, small fiber neuropathy, and hormone-independent pain, rather than just treating symptoms one at a time. That’s a meaningfully different conversation than the one our community has had to have for the last twenty years.

We’ll keep watching this space together. Stay tuned as I’ll keep you informed, and as always — Zebra Strong. 🦓

Jonathan Kost, MD is a board-certified anesthesiologist and interventional pain medicine specialist, founder of the Connecticut Pain Society, medical director and owner of Connecticut’s only EDS-internationally certified pain management center.and author of The Hypermobile EDS Survival Handbook (soon to be released on Amazon).

Medical Disclaimer: This article is for informational and educational purposes only and does not constitute medical advice. It is not a substitute for professional medical evaluation, diagnosis, or treatment. Always consult your physician or a qualified healthcare provider regarding any medical condition, including hypermobile EDS or related hypermobility disorders.

A new study out of Italy, done in partnership with the Ehlers-Danlos Society and published in the journal Clinical Proteomics, just gave that frustration some real scientific weight.

What the researchers did

The team took blood samples from 352 people: 88 with hEDS, 88 with HSD, and 176 healthy people for comparison, drawn from both Italy and the U.S. Using a very sensitive blood test, they measured levels of 458 different proteins, the tiny molecules that circulate in blood and reflect what’s happening inside the body, including inflammation, nerve health, heart and metabolic function, and tissue damage.

What they found

Compared to healthy people, 54 proteins were abnormal in the hEDS group, and 49 were abnormal in the HSD group, and most of those were the same proteins showing up in both lists.

Here’s the key finding: when the researchers compared hEDS patients directly to HSD patients, they found no meaningful differences at all. Not one protein reliably told the two groups apart. They even checked whether Italian and American patients looked different from each other, and again, no real differences showed up.

So the researchers combined everyone with hEDS or HSD into one big group and compared them to the healthy controls. That comparison turned up 69 proteins that were consistently abnormal, 50 elevated and 19 lower than normal, spread across every category they tested. In other words, this doesn’t look like a narrow, one-system problem. It looks like something affecting the whole body.

What those proteins seem to be pointing to

Two patterns stood out.

The first is inflammation and immune system dysfunction. Several of the elevated proteins are ones already tied to inflammatory joint diseases like rheumatoid arthritis and lupus. The single most elevated protein, called MIF, is a well-known driver of inflammation elsewhere in the body.

The second pattern involves the nervous system, specifically, proteins related to the health of nerve-insulating cells called Schwann cells. That’s notable, since nerve pain and small-fiber neuropathy are extremely common complaints in this patient population.

The researchers also used some computer modeling (machine learning) to narrow the original 69 proteins down to a shortlist of 17 that seemed most useful for telling patients apart from healthy people, with three in particular — MYOC, TOP2B, and INPPL1 — rising to the top.

Why this is a big deal

This is the largest, most careful side-by-side comparison of hEDS and HSD blood chemistry done so far, and it backs up something many patients and clinicians have suspected for a long time: the dividing line between hEDS and HSD may not be a real biological line at all. It may just be an artificial cutoff built into the diagnostic paperwork.

This also adds to a growing body of evidence that hEDS and HSD aren’t simply “connective tissue problems.” Immune system dysfunction and low-grade, chronic inflammation appear to be a real and measurable part of the disease, which may help explain why so many patients also deal with mast cell issues, autoimmune-like symptoms, and nerve pain.

What this study does NOT prove yet

The researchers themselves are careful to point out the limits here. These 69 proteins are early candidates, not an approved diagnostic blood test. They haven’t been confirmed yet using other lab methods. The study only captured one moment in time for each patient, not how these proteins might change over months or years. And because it looked at a preselected list of proteins rather than every protein in the body, there could be other important signals it simply didn’t check for.

Still, for a patient community that waits an average of 10 to 20+ years for a correct diagnosis, often after being told their symptoms are “just anxiety” or “in their head”, this kind of research matters. It’s a meaningful step toward an objective blood test, and toward finally proving, in hard biological data, what patients have been saying about their bodies all along.

Reference: Cinquina V, Carini G, Chiarelli N, et al. “Proximity extension assay-based serum proteomic profiling identifies shared protein signatures in hypermobile Ehlers–Danlos syndrome and hypermobility spectrum disorders.” Clinical Proteomics 23, 20 (2026).

Dr. Jonathan Kost is a board-certified anesthesiologist and interventional pain medicine specialist, founder of the Connecticut Pain Society, medical director and owner of Connecticut’s only EDS-internationally certified pain management center.and author of The Hypermobile EDS Survival Handbook (soon to be released on Amazon).

Medical Disclaimer: This article is for informational and educational purposes only and does not constitute medical advice. It is not a substitute for professional medical evaluation, diagnosis, or treatment. Always consult your physician or a qualified healthcare provider regarding any medical condition, including hypermobile EDS or related hypermobility disorders.

Let’s break down why zebras and crooked spines go together, how your pelvis might be the sneaky ringleader, and how a good clinician actually checks for it.

Your Spine

Think of your spine less like a rigid flagpole and more like a circus tent pole, it doesn’t stand up on its own. It’s held vertical by a whole network of ligaments, muscles, and joint capsules acting like tent ropes, tensioned just right to keep everything centered.

Now imagine those tent ropes are made of bungee cord instead of taut nylon. That’s essentially what’s happening in hypermobile EDS. The collagen that’s supposed to give ligaments their “don’t stretch past this point” quality is built a little differently, so those spinal tent ropes give more than they should. Add the fact that muscle tone tends to run lower in hEDS too (less backup support from the muscular system), and you’ve got a spine that’s structurally more free to drift off-center, especially during growth spurts, when everything is lengthening and changing shape at once.

There’s also a more serious cousin in the EDS family worth knowing about: kyphoscoliotic EDS (kEDS), a rarer subtype where significant spinal curvature is actually part of the diagnostic picture, not just a common association. That’s a different animal from the garden-variety postural or functional scoliosis many hypermobile folks develop, but it’s worth mentioning so nobody panics unnecessarily, or dismisses a curve that actually needs a closer look.

Enter the Pelvis: The Foundation Nobody Talks About

Here’s the part that surprises people: a lot of “spine problems” actually start below the spine, at the pelvis.

Your pelvis is the base your entire spinal column sits on. If that base is level, your spine has a fair shot at growing and sitting up straight. If that base is tilted, one side higher than the other, or rotated forward on one side, your spine has to compensate just to keep your head over your feet. Do that for years, especially through adolescence, and a temporary compensation can turn into a fixed structural curve.

Why would the pelvis tilt in the first place? Because the sacroiliac (SI) joints, where your spine’s base connects to your pelvic bones, are basically all ligament, no bony lock-and-key. In a body with typical collagen, that’s fine. In a body with hypermobile collagen, the SI joints are some of the most likely joints to become unstable, because they were relying almost entirely on ligament tension to begin with.

Here’s the sneaky part: a rotated pelvis doesn’t just tilt sideways, it can create the illusion of one leg being shorter than the other, even when both legs are exactly the same length. This is called an “apparent” leg length discrepancy, and it trips up a lot of people (and unfortunately, sometimes clinicians too) into chasing a leg-length problem that isn’t really there.

What This Looks Like

Same leg bones. Same length, top to bottom. The only thing that changed is the angle of the platform they’re hanging from. But if someone eyeballs your standing posture, or even measures from your belly button to your ankle, that tilt can make one leg look shorter, sending you down a rabbit hole of shoe lifts and orthotics that don’t actually fix the real issue upstream.

So How Does a Clinician Actually Check for This?

If you suspect (or your provider suspects) a rotated pelvis is part of your picture, here’s roughly what a thorough hands-on evaluation looks like:

·      Comparing bony landmarks side to side. Your provider will feel for the ASIS (the bony points at the front of your hip bones) and PSIS (the matching points around back), checking whether they sit level, and whether one is riding higher or lower than the other.

·      Standing vs. sitting comparison. If your hips look uneven standing up but level out once you sit down, that’s a big clue the issue is pelvic rotation or SI joint instability, not an actual difference in leg bone length.

·      Watching you move, not just stand still. Tests like having you bend forward or lift one knee toward your chest while your provider tracks how your pelvic landmarks move, help figure out which side is driving the imbalance.

·      A cluster of hands-on provocation tests. A set of maneuvers that gently stress the SI joint from different angles helps confirm whether that joint is the pain generator and the source of instability.

·      Imaging when it’s needed. Standing, full-length X-rays that capture the spine and the pelvis in the same shot let your provider see the whole chain at once, how much your spine curves, and whether your pelvis is tilted underneath it.

The big takeaway: nobody should be fitting you for a shoe lift based on a single tape-measure reading. A proper eval looks at the whole chain, pelvis, SI joints, and spine together, because in EDS bodies, they’re rarely acting independently.

A Confession From the Clinic: This Is Almost Everybody

Here’s something I’ll say plainly after years of examining EDS patients: the majority of the hypermobile EDS patients I evaluate have a rotated pelvis. Not “some.” Not “occasionally.” The majority, with an associated spectrum of symptoms. If you have hEDS and nobody has ever checked your pelvis for rotation, there’s a good chance that’s a gap in your workup worth closing.

There’s actually a simple, low-tech way to get a feel for this yourself (or watch your provider do it), no imaging required:

1.        Lie flat on your back.

2.        Have someone gently raise both of your legs together, then set them back down slowly. This motion helps “reset” the pelvis into a more neutral rotational position rather than whatever asymmetric position it’s been sitting in.

3.        With your legs back down and relaxed, compare the position of your ankles/heels side by side.

In someone with a rotated pelvis, one leg will often look shorter than the other in this position, even though it isn’t. That apparent shortening is the rotation talking, not your actual bones. It’s the same “artificial” leg length discrepancy discussed above, just demonstrated in a quick, low-tech way lying down instead of standing.

SI Belts, Injections, and What Actually Helps

Once a rotated or unstable SI joint is suspected as a driver, there are a few tools that help both confirm the diagnosis and treat it:

·      SI belts. A simple external belt worn around the pelvis that compresses and supports the SI joints. It won’t fix underlying ligament laxity, but it can meaningfully reduce symptoms and functional instability, and the degree of relief it provides is itself diagnostically useful.

·      Physical therapy by a physical therapist, who understands pelvic rotation in EDS patients, can be very helpful.

·      Diagnostic SI joint injection. Injecting the joint with a small amount of anesthetic and watching whether your pain resolves is one of the most reliable ways to confirm the SI joint (rather than the spine, hip, or somewhere else) is the actual source of the problem.

·      SI joint PRP injections. Platelet-rich plasma injected into the joint and its supporting ligaments is a regenerative option some patients pursue to try to improve the durability and support of that lax ligamentous complex.

·      SI fusion — rarely, and only in severe cases. For a small subset of patients with significant, refractory instability, surgical fusion of the SI joint is an option. But here’s the critical piece that’s too often skipped: the pelvis needs to be set into correct rotational alignment before it’s fused in place. Fuse a joint while it’s still rotated, and you’ve permanently locked in the very problem you were trying to fix. This step is under-appreciated and, frankly, rarely done with the attention it deserves.

The Zebra Bottom Line

Scoliosis in EDS isn’t random bad luck, it’s a pretty logical outcome of stretchier-than-average ligaments trying to hold up a spine, often with an unstable pelvic foundation adding insult to injury. Understanding that connection matters, because treating the curve without addressing the pelvis (or vice versa) tends to be like mopping the floor without turning off the faucet.

If your spine curves and your hips never quite look even in photos, this might be why. Bring it up with your provider, ask about a pelvic rotation check (hopefully they know how), and know that there’s a real diagnostic and treatment pathway here, from something as simple as an SI belt to, in rare selected cases, a properly aligned fusion.

Dr. Jonathan Kost is a board-certified anesthesiologist and interventional pain medicine specialist, founder of the Connecticut Pain Society, medical director and owner of Connecticut’s only EDS-internationally certified pain management center.and author of The Hypermobile EDS Survival Handbook (soon to be released on Amazon).

Medical Disclaimer: This article is for informational and educational purposes only and does not constitute medical advice. It is not a substitute for professional medical evaluation, diagnosis, or treatment. Always consult your physician or a qualified healthcare provider regarding any medical condition, including hypermobile EDS or related hypermobility disorders.

Gastrointestinal complaints are among the most common — and most under-recognized — issues faced by people with hypermobile Ehlers-Danlos Syndrome (hEDS). Bloating, irregular motility, food reactions, and vague abdominal discomfort are often dismissed as “IBS” without a deeper look at what is actually happening inside the gut. The connective tissue differences that define hEDS do not stop at the joints and skin; they extend to the structural and functional integrity of the digestive tract itself.

A GI-MAP (GI Microbial Assay Plus) is a stool test that uses quantitative PCR to measure pathogens, commensal (“good”) bacteria, opportunistic organisms, parasites, fungi, and key markers of digestion, inflammation, and immune function. For many zebras, this test offers a window into why symptoms persist even when standard bloodwork and endoscopy come back “normal.”

How hEDS Physiology Shapes the Gut Microbiome

Several features of hEDS predispose the digestive system to dysbiosis (an imbalance of gut microorganisms) and reduced mucosal defense:

•     Visceral hypotonia and delayed motility from collagen laxity, which slows transit and allows bacterial overgrowth

•     Vagal and autonomic dysfunction (often overlapping with POTS), which impairs normal digestive signaling

•     Mast cell activation, which alters gut permeability and inflammatory tone

•     Chronic stress and HPA-axis dysregulation, which can suppress mucosal immune defenses such as secretory IgA

•     A history of frequent antibiotic exposure, which can shift the microbial balance toward opportunistic organisms

The result is a pattern seen repeatedly on GI-MAP testing in this population: normal inflammatory and pathogen markers, but low-grade opportunistic overgrowth paired with reduced immune surveillance. This is a functional disruption rather than an infectious or inflammatory disease process — an important distinction when interpreting results and choosing treatment.

hEDS Comorbidities and Their GI-MAP Signatures

The table below summarizes the most common hEDS-associated comorbidities, how each one affects the gut, what those effects tend to look like on a GI-MAP report, and general treatment directions clinicians commonly consider. This is intended as an educational reference — not a substitute for individualized medical evaluation.

A General Treatment Framework

While every plan should be individualized to the person's specific GI-MAP findings and symptoms, most functional GI protocols for hEDS-associated dysbiosis follow a similar phased structure:

Phase 1 — Reduce Opportunistic Overgrowth (weeks 1–4)

Botanical antimicrobials such as oregano oil, berberine, or garlic-derived compounds are typically tried first when inflammatory markers (calprotectin, occult blood) are normal. Prescription antimicrobials are generally reserved for refractory or clearly symptomatic overgrowth.

Phase 2 — Support Mucosal Immunity (weeks 1–12, overlapping)

Because low secretory IgA is such a common finding in this population, immune-supportive agents — colostrum or serum-derived bovine immunoglobulins, Saccharomyces boulardii, and attention to the HPA axis and stress load — are introduced early and continued through the rebuilding phase.

Phase 3 — Rebuild the Microbiome (weeks 4–12)

Once overgrowth organisms are addressed, multi-strain probiotics, prebiotic fibers (such as partially hydrolyzed guar gum or acacia), and dietary fiber diversity help restore keystone species like Akkermansia muciniphila and Faecalibacterium prausnitzii, and help normalize the Firmicutes:Bacteroidetes ratio.

Retesting

A repeat GI-MAP at 8–12 weeks after completing a protocol is the most reliable way to confirm that overgrowth organisms have cleared and that secretory IgA and other markers have normalized.

Key Takeaway for Zebras

•  A GI-MAP that shows no pathogens and normal inflammatory markers does not mean the gut is functioning normally.

•  In hEDS, the more common pattern is a functional one: opportunistic overgrowth, reduced mucosal immune defense, and a skewed microbial balance — all tied back to the same connective tissue and autonomic differences that affect the rest of the body.

•  Bring your GI-MAP results to a provider familiar with hEDS and its comorbidities (MCAS, POTS, dysautonomia) for the most accurate interpretation.

Dr. Jonathan Kost is a board-certified anesthesiologist and interventional pain medicine specialist, founder of the Connecticut Pain Society, medical director and owner of Connecticut’s only EDS-internationally certified pain management center.and author of The Hypermobile EDS Survival Handbook (soon to be released on Amazon).

Medical Disclaimer: This article is for informational and educational purposes only and does not constitute medical advice. It is not a substitute for professional medical evaluation, diagnosis, or treatment. Always consult your physician or a qualified healthcare provider regarding any medical condition, including hypermobile EDS or related hypermobility disorders.

What the researchers did

The team followed 41 children and teens (average age 11) diagnosed with some form of EDS or hypermobility spectrum disorder (HSD) at a major pediatric genetics center between 2018 and 2024. About 6 in 10 fell into the hEDS/HSD category, the group without a known genetic marker, while the rest had genetically confirmed subtypes like classical or vascular EDS. Most underwent genetic testing, and researchers tracked everything from joint symptoms to skin findings to mental health.

The findings that matter most for families

Joint pain and instability dominate, but fractures are rare. Musculoskeletal symptoms affected over 90% of the children, with chronic joint pain the single most common complaint. Flat feet were common too. Reassuringly, actual bone fractures were uncommon, hypermobility causes a lot of discomfort, but it isn’t generally a fracture risk in the way some parents fear.

Mental health symptoms are common, and worth taking seriously early. Anxiety and depression showed up in over half the children with hEDS or HSD, and the likelihood increased with age. This echoes a growing body of research linking joint hypermobility to anxiety disorders. The takeaway for families: a child with hypermobility who develops anxiety isn’t experiencing something unrelated to their joints, the two may share underlying biology. Early mental health screening deserves a permanent place in routine care, not an afterthought.

Skin changes can help sort out subtypes. Easy bruising and stretchy skin were common across the board, but one detail stood out: children with hEDS had notably less of the thin, “tissue-paper” atrophic scarring that’s typical of classical EDS. That’s a clinically useful clue when a geneticist is trying to sort out which type of EDS is in play.

Cardiac findings were mild and reassuring. About a quarter of children had some cardiovascular finding, most often fainting (syncope) rather than a structural heart problem. No child in this cohort had aortic root dilation or any life-threatening cardiac issue. The researchers suspect dysautonomia, problems with the autonomic nervous system that regulates heart rate and blood pressure, is the more likely explanation for the fainting episodes than a structural defect. This is a reassuring data point for parents who hear “EDS” and immediately worry about the heart.

Headaches and stomach pain travel together. Chronic abdominal pain was significantly linked to migraines in this cohort; a pattern the researchers suggest may point to shared dysautonomia or nervous system involvement rather than two unrelated problems.

Genetics still can’t diagnose hEDS itself. This is the sobering part. While the team found genetically confirmed mutations in every case of classical, vascular, kyphoscoliotic, and arthrochalasia EDS, they still could not find a definitive genetic marker for hEDS itself, consistent with every major study before it. Some children had “variants of uncertain significance” in genes like TNXB, ELN, and PIEZO2, but these need further research before they can be called diagnostic.

Why this matters beyond the data

Perhaps the most clinically useful contribution of this study isn’t a single finding, it’s the case the authors make for caution on both ends. They explicitly warn against over-labeling a hypermobile but otherwise asymptomatic child with a diagnosis like hEDS, given the psychological weight that label can carry. At the same time, they push back against under-diagnosing kids whose hypermobility comes bundled with pain, fainting spells, or anxiety. Their suggested approach: when joint hypermobility shows up with dysautonomia or psychological symptoms, that combination deserves a real workup, not reassurance alone.

The researchers also point to a newer pediatric-specific framework (proposed in 2023 by Tofts and colleagues) that’s better suited to growing bodies than the adult-oriented 2017 criteria most of us still use. It hasn’t been widely adopted yet, but it’s a sign of where pediatric diagnostic thinking is heading, and worth watching as the EDS Society’s own “Road to 2026” criteria update unfolds this year.

The bottom line

This study won’t change how hEDS is diagnosed tomorrow. But it reinforces a pattern this newsletter keeps returning to: hEDS isn’t just a joint problem dressed up in different clothes for kids versus adults. It’s a multisystem condition where the nervous system, the gut, the skin, and mental health are all genuinely connected and that’s true starting in childhood, not something that develops later. For parents navigating a new diagnosis, the most useful question isn’t just “how flexible is my child’s body,” but “what else is going on alongside it.”

https://pmc.ncbi.nlm.nih.gov/articles/PMC12386060/

Dr. Jonathan Kost is a board-certified anesthesiologist and interventional pain medicine specialist, founder of the Connecticut Pain Society, medical director and owner of Connecticut’s only EDS-internationally certified pain management center.and author of The Hypermobile EDS Survival Handbook (soon to be released on Amazon).

Medical Disclaimer: This article is for informational and educational purposes only and does not constitute medical advice. It is not a substitute for professional medical evaluation, diagnosis, or treatment. Always consult your physician or a qualified healthcare provider regarding any medical condition, including hypermobile EDS or related hypermobility disorders, especially in children.

POTS is a syndrome, not a disease. That means it’s a cluster of symptoms, the racing heart on standing, the lightheadedness, the fatigue, the brain fog, that can be produced by several different underlying mechanisms. A beta blocker slows the heart rate. Salt and fluids expand blood volume. Compression stockings reduce venous pooling. All of these are legitimate, evidence-based, first-line tools, and for many patients they genuinely make daily life more livable. But none of them ask, let alone answer, the question that matters most for long-term improvement: why is your autonomic nervous system doing this in the first place?

For the hEDS community specifically, that question deserves a more detailed answer. So let’s walk through the four mechanisms that the research actually shows, and how each one intersects with hypermobile connective tissue.

1. Post-viral injury, especially post-COVID

POTS has been recognized for decades as something that can follow a viral illness, but COVID-19 turned this from a clinical footnote into a major area of research. Estimates suggest that somewhere between roughly 2% and 14% of COVID-19 survivors go on to develop true POTS, with a much larger share, up to roughly 60% in some cohorts — experiencing POTS-like symptoms such as tachycardia, orthostatic intolerance, and cognitive impairment within six to eight months of infection.

The proposed mechanisms are still being worked out, but the leading candidates include autoantibodies that cross-react with autonomic nerve fibers and receptors, direct viral injury to small autonomic nerve fibers, persistent low-grade inflammation, and dysregulation of the renin-angiotensin-aldosterone system that controls blood volume. Notably, the same research literature that describes post-COVID POTS specifically flags joint hypermobility, particularly EDS, as a pre-existing condition that shows up disproportionately in these patients. The leading theory is that an already-vulnerable autonomic and connective tissue system has less reserve to absorb a viral hit, whether that hit comes from COVID, Epstein-Barr, or another trigger entirely.

The clinical takeaway: if your POTS started or significantly worsened after an infection, that history matters. It can point toward an autoimmune or post-infectious workup rather than treating the tachycardia in isolation.

2. Low iron stores — even without anemia

This is one of the most under appreciated and easily checked drivers. Multiple studies have found that POTS patients have meaningfully lower serum ferritin than people without POTS, and the relationship holds even in patients who aren’t anemic by standard hemoglobin cutoffs. In one case-control study, patients with ferritin below 50 ng/mL were nearly three times more likely to have POTS. In adolescents specifically, low iron storage was found in half of POTS patients compared with about 14% of the general pediatric population.

The proposed mechanism involves nitric oxide. Iron deficiency is associated with increased nitric oxide production, which promotes excessive vasodilation, exactly the kind of vascular over-relaxation that can worsen blood pooling and orthostatic intolerance. This is now moving from theory into intervention: Vanderbilt’s Autonomic Dysfunction Center is currently running a clinical trial giving iron to POTS patients with low ferritin to see whether it improves blood volume and symptoms, building on earlier observational data suggesting a meaningful share of iron-deficient POTS patients improve with repletion.

Ferritin under 45–50 ng/mL is not “normal” just because it’s not flagged as abnormal on a standard lab report. If your ferritin hasn’t been checked or was checked and dismissed because your hemoglobin was fine, that’s worth revisiting. I have seen countless individuals respond to ferritin supplementation in clinical practice.

3. Dysglycemia — the blood sugar rollercoaster

This one is subtle because it can look exactly like a “POTS flare” without anyone connecting it to food. The chronic hyperadrenergic state seen in many POTS patients, elevated norepinephrine and epinephrine, reduces insulin sensitivity. Combine that with the GI dysmotility that’s also common in dysautonomia (and very common in hEDS, given the connective tissue support of the gut), and you get a setup where carbohydrate-heavy meals move too quickly into the small intestine, trigger an exaggerated insulin response, and produce a real, measurable drop in blood sugar two to three hours later. That drop forces the body to release a fresh wave of cortisol, adrenaline, and norepinephrine to bring glucose back up, which is precisely the chemical cocktail that produces the shakiness, palpitations, and anxiety patients describe as a “crash.”

One observational glucose-tolerance study found that roughly 40% of POTS patients showed abnormally low glucose several hours into testing. Case reports have also documented patients with normal A1c and fasting glucose who nonetheless had clearly demonstrated reactive hypoglycemia driving their orthostatic symptoms, meaning a single fasting glucose or A1c is not enough to rule this out. A proper evaluation generally requires either an extended oral glucose tolerance test or continuous glucose monitoring data correlated with symptom timing.

4. Cortisol and HPA axis dysregulation

Cortisol’s role in POTS is intertwined with the dysglycemia picture above, it’s the hormone the body releases to course-correct a glucose drop, but it also has a more chronic dimension. The autonomic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis are deeply cross-wired; chronic orthostatic stress, chronic pain, and the cumulative physiologic burden of living with hEDS can all push the HPA axis toward dysregulation, with blunted or erratic cortisol rhythms rather than a normal morning peak and evening trough. That, in turn, feeds back into worse glucose regulation and a more reactive sympathetic nervous system, creating a loop that compounds rather than resolves on its own.

This is the hardest of the four to test cleanly, a single random cortisol level usually isn’t enough, and patterns matter more than any one number, but it’s also why “just calm down” or “manage your stress” is such an unsatisfying answer to patients who are clearly doing everything right and still flaring. The dysregulation is physiological, not a failure of coping.

Where this leaves the hEDS patient

None of this means your beta blocker, your salt tablets, your compression stockings, or your IV fluids are wrong. They’re appropriate first-line, symptom-directed therapy, and stopping them without a plan is not the takeaway here. What it does mean is that “symptom-controlled” and “explained” are two different things, and for hypermobile patients in particular, who already carry a connective tissue and vascular predisposition to orthostatic intolerance, it’s worth asking your physician for the additional layer of workup: a ferritin level (not just hemoglobin), a real assessment of post-meal glucose patterns rather than a single fasting draw, a review of whether your POTS onset tracked with an infection, and a conversation about HPA axis function if fatigue and flares feel disproportionate to your activity level.  HPA tests examples include morning (8am) serum cortisol and ACTH, 4-point salivary cortisol, ACTH stimulation test, CRH stimulation test, DHEA-S, Fasting glucose or, better, a glucose tolerance curve with cortisol drawn alongside it).

Four mechanisms rarely act in isolation, and you may have more than one driving your symptoms simultaneously. But each one you identify and address is one less thing the beta blocker has to compensate for, and one step closer to treating the syndrome instead of just the heart rate.

Dr. Jonathan A. Kost, MD, is a board-certified anesthesiologist and interventional pain medicine specialist, founder of the Connecticut Pain Society, and former director of Connecticut’s only EDS International Center of Excellence. This article is for educational purposes only and does not constitute medical advice. Please discuss any changes to your evaluation or treatment plan with your own physician.

I want to take this seriously, because the core feeling behind it is completely valid. POTS is a real physical condition, not “just anxiety,” and a lot of patients have been brushed off for years by doctors who stopped looking once a basic blood test came back fine. But just because the feeling behind the video is right doesn’t mean every claim in it is. Some parts have solid science behind them. Other parts are guesses dressed up to sound like facts. Let’s go through it in plain language.

The part with the best evidence: your immune system may be attacking your own nerves

This is the strongest piece of the whole video, in my opinion. Starting back in 2014, researchers found that a lot of POTS patients have something called autoantibodies floating around in their blood. Normally, antibodies are your immune system’s tool for fighting off germs. But sometimes the immune system makes a mistake and creates antibodies that attack your own body instead. In POTS, these misguided antibodies seem to target the same nerve receptors that control your heart rate and blood vessels.

A study of 55 POTS patients found that most of them had at least one of these antibodies showing up at high levels. Researchers have even injected these antibodies into rabbits and watched the rabbits develop POTS-like symptoms, which is a pretty strong sign this isn’t just a coincidence.

This lines up with something a lot of you already know firsthand: POTS often shows up suddenly after a bad infection, like a virus, Lyme disease, or COVID, rather than slowly creeping in. That pattern fits an immune system that got triggered by an infection and never fully calmed back down.

The honest caveat: this isn’t 100% settled science yet. A large 2024 study actually found no difference in these antibody levels between POTS patients and healthy people, and even researchers in this field admit that the current blood tests for these antibodies might not be accurate enough to use for diagnosis yet. So the fair takeaway is: this is a genuinely promising lead that doctors are still working out, not something you can get tested for at your average lab and use to confirm a diagnosis today.

Bottom line: Real and promising, but still being figured out. Worth asking your doctor about, especially if your POTS started right after an illness.

The shakier part: the “12 genes” list

One video names a string of genes — MTHFR, COMT, and others with equally unpronounceable names and claims each one is a piece of your POTS puzzle, with a specific supplement to fix it. These genes are real, and the basic biology described isn’t made up. The problem is the jump from “this gene is involved in a process related to blood pressure or stress hormones” to “this exact variant is causing your POTS, and this supplement will fix it.” That’s a much bigger leap than the video lets on.

A few reasons to be cautious:

Many of these gene variants are incredibly common. For example, something like 40 to 60% of all people carry at least one MTHFR variant, and the vast majority of those people don’t have POTS. A genetic variant that common simply can’t be the main cause of a condition that affects a much smaller number of people. At most, these variants might nudge your risk slightly, on top of other things going on in your body.

A lot of the original research behind these claims comes from small, older studies looking at one gene at a time. This type of study has a long track record of producing exciting-sounding results that don’t hold up when bigger, more rigorous studies are done later. As far as I can find, none of these genes have been confirmed in a large, well-designed study specifically on POTS patients.

The supplement suggestions (folate for one gene, magnesium for another, and so on) make sense on paper, but I couldn’t find solid clinical trials proving they actually help POTS symptoms. That doesn’t mean they’re useless, many are low-risk and worth a conversation with your doctor, but it’s a guess based on a plausible theory, not a proven fix.

Bottom line: Interesting theories, not proven facts. Treat any “your genes explain everything” claim with a healthy dose of skepticism, especially if it comes with a product to buy.

The part that’s really just one doctor’s personal theory

Near the end, this particular video mentions a gene cluster called RCCX, including a gene called CYP21A2, as tying together POTS, hypermobility, mast cell issues, and more. This one is worth knowing the backstory on: this isn’t a widely accepted scientific finding. It comes from one physician, Dr. Sharon Meglathery, who developed this theory based on her own illness and her observations of patients over the years. It’s a thoughtful and interesting idea, and it does match something many of us notice, that hypermobility, dysautonomia, and mast cell symptoms tend to run together in the same people and families. But noticing that something happens together is different from proving why it happens together, and this particular theory hasn’t been tested in the kind of large, controlled studies that would let scientists confirm it.

Bottom line: An interesting idea from one doctor’s clinical experience, not an established scientific fact. Fine to be curious about, not something to build a treatment plan around yet.

The part your body already knows is true: POTS, mast cells, and hypermobility travel together

Here’s the piece I’d actually want you to walk away remembering. Even though scientists haven’t fully figured out why yet, doctors who treat this population see it constantly: POTS, mast cell activation, and hypermobility (like hEDS) show up together in the same patients over and over. You flush, your heart races, you crash after a hot shower or a meal, and three different specialists have each only looked at their own piece of the puzzle. You don’t need a genetic test to know that pattern is real if you’ve lived through it. The genetics behind it are still being worked out, but the pattern itself is well recognized and worth naming clearly to your care team.

So what should you actually do with all this?

If this video resonated with you, here’s a more grounded way to think about next steps:

If your POTS started suddenly after an infection, it’s reasonable to ask your doctor about autonomic testing or autoimmune workup. This is the area with the most real evidence behind it, even though it’s not yet a routine, simple blood test everywhere.

Be skeptical of any product that promises a personalized supplement plan based on a genetic test. The science behind individual genes is still early and shaky. A trial of something low-risk like magnesium or a B vitamin is reasonable to discuss with your doctor, but it should be framed as “let’s try this because it’s safe and makes biological sense,” not “your genes proved this will fix you.”

Don’t let an unproven theory replace the testing we already have available. Mast cell testing, tilt table testing, a careful review of medications and triggers, and basic bloodwork are still the foundation, even while research on the genetic and immune side continues.

And most importantly: hold onto both truths at once. Your symptoms are real and have a physical basis, and the full explanation for why is still being written by researchers. That’s not the same as being dismissed, it just means the science hasn’t fully caught up yet to what patients already know about their own bodies.

The instinct behind that video, that POTS patients deserve more than “your labs are normal, it’s probably stress”,  is something I agree with completely. The goal now is making sure the explanations we reach for are as solid as the symptoms they’re trying to explain.

The Zebra Times is written by Dr. Jonathan A. Kost, MD, board-certified anesthesiologist and interventional pain medicine specialist, and author of The Hypermobile EDS Survival Handbook. Content is educational and does not constitute medical advice.

They are. And a new study is adding hard data to what the zebra community has long suspected.

What the Researchers Found

Using the National Inpatient Sample, a massive database representing millions of U.S. hospitalizations, researchers compared IBS patients who also had EDS against those who didn’t. Two findings stood out.

First, EDS-IBS patients were significantly younger at the time of hospitalization. This tracks with what we know about hEDS, symptoms often emerge in adolescence or early adulthood, but seeing it confirmed in national data gives it real clinical weight. When young patients with EDS are dismissed and told their GI symptoms are stress-related, this pushes back.

Second, EDS-IBS patients used substantially more healthcare resources, longer stays, more procedures, higher costs. This isn’t surprising once you understand the biology, but it matters enormously for how this population should be managed.

Why EDS Makes IBS So Much Harder

IBS in an hEDS patient isn’t just IBS. It’s IBS running on compromised hardware.

The gut wall is rich in collagen. Defective collagen doesn’t stop at your joints, it extends to your intestines, affecting structural integrity and nerve function. Dysautonomia, which is common in hEDS, directly disrupts the autonomic signaling that controls gut motility. Mast cells, overactive in many hEDS patients, line the gut in abundance and drive visceral pain, altered permeability, and motility dysfunction. And visceral hypersensitivity means normal levels of gut activity that wouldn’t register in another person can be genuinely painful for you.

These aren’t separate problems. They’re overlapping biological mechanisms that compound each other, which is exactly why standard IBS treatments often fall short for this community.

What This Means for You

A few practical takeaways:

Your GI doctor should understand EDS. Standard IBS protocols may need significant modification when autonomic dysfunction, connective tissue fragility, and mast cell activation are all in play.

Your more complicated hospital courses are real. EDS-IBS patients are more resource-intensive because their disease genuinely is more complex. That’s physiology, not dramatization.

Push for answers early. The data shows this is a young population being hospitalized. Years of conservative management without addressing the underlying biology has consequences.

The Bigger Picture

When a national database confirms that EDS-IBS patients are younger, sicker, and more resource-intensive than standard IBS patients, it becomes harder to dismiss EDS as a niche concern. It becomes evidence for dedicated care pathways, multidisciplinary treatment, and insurance coverage for the complex management hEDS patients actually require.

Your gut has been telling you something for years. The data is finally starting to agree.

The Zebra Times is written by Dr. Jonathan A. Kost, MD, board-certified anesthesiologist and interventional pain medicine specialist, and author of The Hypermobile EDS Survival Handbook. Content is educational and does not constitute medical advice.

A study published in June 2026 in the journal Polysaccharides adds another piece to that puzzle. It won’t show up in the hEDS literature. It isn’t about connective tissue. The words “Ehlers-Danlos” don’t appear anywhere in it. But if you read it through the lens of what we know about hEDS, and the remarkably high rates of ADHD in the zebra community, it becomes quietly compelling.

Let’s walk through what this research actually found, and why it matters to you.

First: What Even Is ADHD, in Body Terms?

Most people think of ADHD as a behavioral problem, a kid who can’t sit still, an adult who loses their keys, someone who “just needs to try harder.” But ADHD is a neurological condition, rooted in chemistry.

At its core, ADHD involves an imbalance of two brain chemicals you’ve probably heard of: dopamine and norepinephrine. These are the neurotransmitters that help your prefrontal cortex, the “control tower” of the brain, stay online. They govern your ability to focus, regulate emotions, plan ahead, and resist impulses. When dopamine and norepinephrine are low or aren’t working efficiently, the control tower goes offline. The result looks like inattention, hyperactivity, and impulsivity.

This is why stimulant medications like Adderall and Ritalin work, they increase dopamine and norepinephrine availability. And it’s why non-stimulants like atomoxetine (Strattera) also help, they target norepinephrine specifically.

What the research is now revealing is that the gut, and the trillions of bacteria living in it, is one of the upstream regulators of this whole system.

The Study: Seaweed, Rats, and Attention

Researchers at the Chinese Academy of Sciences tested a compound called low molecular weight Fucoidan (LMWF for short) on rats bred to display ADHD-like behavior. Fucoidan is a natural substance found in brown seaweed, specifically Saccharina japonica, the seaweed used in many Asian dishes and supplements. The “low molecular weight” version has been processed into smaller fragments that the body can absorb and use more readily.

These rats, called spontaneously hypertensive rats, or SHR, are the gold standard animal model for ADHD research. They naturally develop hyperactivity, inattention, and impulsivity that mirrors the human condition, and they respond to the same medications used in people.

The researchers gave these rats LMWF daily for three weeks, then put them through a battery of behavioral tests and measured their brain chemistry and gut bacteria.

Here is what they found:

Behavior improved. The LMWF-treated rats were significantly less hyperactive and anxious in the open field test, their movement patterns normalized to look more like healthy controls. In the water maze test, which measures spatial memory and learning, they performed substantially better than untreated ADHD model rats.

Brain chemistry shifted. Dopamine and norepinephrine levels rose in the prefrontal cortex, the exact brain region implicated in ADHD. The genes responsible for producing dopamine were turned up; the gene responsible for “vacuuming up” dopamine too quickly was turned down. This is essentially what ADHD medications aim to accomplish through chemistry. LMWF appeared to achieve something similar through a biological pathway.

The brain looked healthier under the microscope. In the untreated ADHD rats, brain cells in the striatum and cerebellum showed signs of damage — shrinkage, nuclear disruption, signs of cell death. In the LMWF-treated rats, those brain cells looked more normal and preserved.

The gut changed in meaningful ways. Perhaps most interesting for our purposes: LMWF reshaped the rats’ gut microbiome. Beneficial bacteria, including Lactobacillus species, Akkermansia, and Bifidobacterium, increased significantly. Harmful, pro-inflammatory bacteria decreased. The authors concluded that at least part of LMWF’s effect on the brain was traveling through the gut.

The Gut-Brain Highway: A Primer for Zebras

Here is the concept at the heart of this research, and it is one that every person with hEDS should understand: the gut and the brain are in constant two-way communication.

This communication runs through a network called the gut-brain axis, a superhighway of nerve signals, immune messengers, and chemical compounds flowing between your intestines and your central nervous system. The main nerve involved is the vagus nerve, which connects your brainstem directly to your gut. But gut bacteria also produce neurotransmitters and short-chain fatty acids that enter the bloodstream and influence brain function directly.

When your gut microbiome is healthy and diverse, this highway carries constructive signals: anti-inflammatory compounds, precursors to serotonin and dopamine, and molecules that support the integrity of the blood-brain barrier. When your gut microbiome is disrupted, a state called dysbiosis, the signals change. Inflammation rises. Neurotransmitter production falls. The brain, particularly the prefrontal cortex, starts to underperform.

For the average person, this is interesting. For someone with hEDS, this is personally relevant in a way that deserves serious attention.

Why This Matters for hEDS

Here is where the science gets personal for our community.

People with hEDS have dramatically elevated rates of ADHD, studies suggest somewhere between 40 and 60 percent of hEDS patients meet criteria, compared to around 5 to 10 percent in the general population. That is not a coincidence. It is a signal that something about the underlying biology of hEDS predisposes the brain to the same imbalances that drive ADHD.

We don’t yet have a complete explanation, but the gut-brain axis offers a compelling partial answer, because hEDS has profound effects on the gut.

Gastrointestinal dysmotility is one of the most common and under-recognized features of hEDS. Hypermobile connective tissue means hypermobile intestines, slow transit, incomplete emptying, poor mechanical mixing of gut contents. This creates a gut environment that is chronically altered. Food sits longer. Bacteria grow in places they shouldn’t. The microbiome shifts.

Mast cell activation, which frequently accompanies hEDS, adds another layer. Mast cells line the gut in large numbers. When they’re overactive, they release histamine and other inflammatory mediators directly into the intestinal environment. This fuels dysbiosis, damages the intestinal lining, and allows bacterial byproducts to leak into the bloodstream, a process sometimes called leaky gut, which then feeds inflammatory signals up to the brain.

Dysautonomia, the dysfunction of the autonomic nervous system that is almost universal in hEDS, directly affects vagal tone, the activity of that main gut-brain communication nerve. Reduced vagal tone impairs both gut motility and the brain’s ability to receive and process calming, regulatory signals.

Add these up, and you have a population of patients whose gut-brain highway is structurally compromised in multiple ways simultaneously. The downstream effect on dopamine regulation, attention, and executive function is not surprising. It may be, in fact, largely predictable.

The study on LMWF didn’t set out to investigate any of this. But the mechanisms it describes, gut dysbiosis driving neuroinflammation, which impairs dopaminergic signaling, which produces ADHD-like behavior, map almost precisely onto what we’d expect to see in an hEDS patient.

What About LMWF Itself?

You may be wondering: should I go buy fucoidan supplements?

Not so fast, and this is where we need to be honest about what this research is and isn’t.

This was an animal study. Rats are not people. Their gut microbiomes are different. Their brain chemistry is different. The dose used in this study would not translate directly to a human dose, and we have no data yet on whether LMWF would produce similar effects in humans with ADHD, let alone humans with hEDS-related ADHD. Animal studies are the first step in scientific understanding, they generate hypotheses. They do not establish treatments.

This study was not designed to study hEDS. The researchers were not thinking about connective tissue disorders, mast cells, dysautonomia, or the specific gut environment of an hEDS patient. The connections drawn in this article are extrapolations, informed and biologically plausible, but extrapolations, nonetheless.

Fucoidan supplements vary enormously. The LMWF used in this study was carefully prepared with a specific molecular weight (7.2 kDa) and measured sulfate content. Commercial fucoidan supplements on the market are not standardized in this way. Whether they would have similar biological effects is unknown.

Seaweed-derived compounds can interact with medications. Fucoidan has anticoagulant properties and may interact with blood thinners and other medications. Anyone with complex medical needs, which describes most people reading The Zebra Times, should speak with their physician before adding any seaweed-derived supplement.

The Bigger Picture

What this research does contribute, meaningfully, is more evidence that ADHD is not simply a brain disease. It is a whole-body condition that involves the gut, the immune system, and the nervous system in a deeply integrated way. For the hEDS community, where the gut, the immune system, and the nervous system are all simultaneously affected by the underlying connective tissue disorder, this framing is both validating and actionable.

It suggests that supporting gut health is not merely about digestive comfort. It is potentially about supporting brain health. It suggests that the chronic dysbiosis, inflammation, and dysautonomia that characterize hEDS may be upstream contributors to the cognitive and attention difficulties so many zebras experience.

It also reinforces the importance of advocating for integrated, multisystem care. An hEDS patient with ADHD who sees a psychiatrist for stimulant management and a gastroenterologist for motility issues, but who has never had a clinician connect those two conversations, is receiving fragmented care for what may be a unified problem. You deserve a clinician who sees the whole picture.

For more information related to Gut biome testing (IE G.I. map), please refer to my prior Substack article called, The Gut Test Every hEDS Patient Should Know About.

Jonathan A. Kost, MD, is a board-certified anesthesiologist and interventional pain medicine specialist with a subspecialty focus in hypermobile Ehlers-Danlos Syndrome and connective tissue disorders. He is the former director of Connecticut’s only EDS International Center of Excellence, and the author of The Hypermobile EDS Survival Handbook. This article is for educational purposes only and does not constitute medical advice.

Did this article resonate with you? Share it with a zebra who needs to hear it. And if your clinician has never connected your gut symptoms to your brain fog, consider bringing this research to your next appointment, you might start a conversation that changes your care.

But if you have hypermobile Ehlers-Danlos syndrome, this is one prescription worth pausing on before you fill it.

What Cipro actually is:

Cipro belongs to a class of antibiotics called fluoroquinolones (others include Levaquin/levofloxacin and Avelox/moxifloxacin). They’re powerful and broad-spectrum, which is exactly why they get reached for so often. But that power comes with a side-effect profile that lands differently for those whose connective tissue is already fragile.

Why the FDA singled out EDS

In December 2018, the U.S. Food and Drug Administration issued a formal safety warning: fluoroquinolones can increase the risk of tears and ruptures in the aorta, the body’s main artery, and these events, called aortic aneurysms and dissections, can be life-threatening.

Crucially, the FDA named the people at higher risk. The list includes the elderly, people with high blood pressure or existing vascular disease, and people with genetic connective tissue disorders — specifically naming Marfan syndrome and Ehlers-Danlos syndrome.

The collagen link

Here’s the logic in plain terms. Fluoroquinolones appear to interfere with collagen, they can break it down and interfere with the cells that repair it. That’s why this drug class is famous for causing tendon pain and even tendon ruptures (the Achilles tendon especially), sometimes after just a single dose.

Now connect the dots. EDS is, at its core, a disorder of how the body builds and maintains collagen. Adding a medication that further stresses collagen is layering an insult on top of an existing vulnerability. Tendons, ligaments, and the walls of blood vessels are all collagen-rich, so the concern extends from the joints you already worry about to the aorta itself.

An honest word about the aneurysm risk

You deserve the real picture, not just the scary headline. Catastrophic aortic events are far more strongly tied to vascular EDS and Marfan syndrome than to hypermobile EDS, and a handful of large recent studies have even questioned how strong the aortic connection is across the board. The most concrete, well-documented hazard for someone with hEDS is actually the tendon and soft-tissue toxicity, the very tissues that already giving you trouble.

So this isn’t a reason to panic. It’s a reason to be deliberate.

What to do instead

The encouraging news: uncomplicated UTIs almost always have safer alternatives. When you’re handed a Cipro prescription, it’s completely reasonable to ask:

                  •               “Is there a non-fluoroquinolone option that would work for me?” Antibiotics like nitrofurantoin, trimethoprim-sulfamethoxazole, or certain cephalosporins are often first-line for simple UTIs.

                  •               “I have Ehlers-Danlos syndrome, does that change what you’d prescribe?” Many clinicians simply don’t have EDS top of mind in a busy UTI visit.

There are times when a fluoroquinolone truly is the best or only option, a resistant infection, an allergy to alternatives, certain complicated cases. In those situations, taking it can be the right call. The goal isn’t to refuse Cipro forever; it’s to make sure it’s a deliberate choice rather than a default.

If you ever do take a fluoroquinolone and develop sudden tendon pain, or far more rarely, chest, back, or abdominal pain, stop and seek care right away.

The takeaway

Carry this one with you the way you carry the rest of your zebra knowledge: a UTI is rarely an emergency that demands Cipro specifically. A two-minute conversation with whoever is writing the prescription can swap it for something that does the same job without poking at the collagen we already have to protect.

For educational purposes only. This is not medical advice and does not replace care from your own provider, nor does it create a physician-patient relationship. Consult your clinician before making any medical or medication decision. In an emergency, call your local emergency number.

If you live with hypermobile Ehlers-Danlos Syndrome, your gut has probably caused you more grief than you can count. The constipation that laughs at laxatives. The bloating that arrives uninvited every afternoon. The doctor who handed you an IBS diagnosis like it was an answer, when really it just felt like a door closing. You know exactly what we're talking about.

A new study published in January 2026 won't fix all of that tomorrow. But it does something that matters enormously to this community: it uses the science of genetics to show in a study of over 268,000 people, that gut speed is deeply tied to our biology. And the biggest unexpected finding? A common vitamin most of us rarely think about: vitamin B1.

First: Why Should an IBS Study Matter to You?

Because IBS and hEDS aren't just occasional neighbors, they're remarkably intertwined. Researchers at Queen Mary University in London found that roughly 40% of people diagnosed with IBS also have hEDS. And when scientists looked at it from the other direction — studying people already diagnosed with hEDS — more than 60% reported significant gut problems right from the time of their EDS diagnosis. This is not a coincidence. There is something deeper going on biologically.

62% of hEDS patients report significant GI symptoms at time of diagnosis

~40% of IBS patients also meet hEDS diagnostic criteria

76% of hEDS patients who underwent formal motility testing had measurable dysmotility

When hEDS patients were formally tested for gut motility problems — meaning how well food and waste actually move through the digestive system — a striking 76% had some measurable issue. Problems ranged from a sluggish stomach (gastroparesis) to a slow-moving colon. And one of the strongest predictors of gut problems in hEDS? POTS — the heart rate and blood pressure condition that many of you also live with. This tells us something crucial: the gut problems in hEDS aren't just about loose tissue letting organs shift around. The nervous system that runs your gut is also involved.

What the New Study Actually Found

A team of international researchers studied the DNA of 268,606 people from European and East Asian backgrounds. They were looking for differences in people's genes that could explain why some people have very frequent bowel movements while others are chronically constipated. Think of it like finding the hidden dials in your DNA that control how fast or slow your gut runs.

They found 21 locations in the human genome linked to gut speed. The loudest signal of all pointed to a gene called SLC35F3 — whose job is to carry vitamin B1 into your cells. This gene is active in both the brain and the gut, which makes sense: the gut has its own nervous system (sometimes called the 'second brain'), and both need to communicate properly for digestion to work. A second important gene, XPR1, helps convert vitamin B1 into the active form your body can actually use. If that gene isn't working efficiently, it doesn't matter how much B1 you eat — your body may not be able to put it to work.

"We used genetics to build a roadmap of biological pathways that set the gut's pace. What stood out was how strongly the data pointed to vitamin B1 metabolism, alongside established mechanisms like bile acids and nerve signalling."

— Dr. Cristian Díaz-Muñoz, lead author

The researchers then checked this in the real world, looking at dietary data from nearly 100,000 people: those who ate more vitamin B1 in their diet did tend to have more frequent bowel movements — but only depending on which version of the gene they carried. This is a key insight. It's not just about what you eat. It's about whether your genes allow you to actually use what you eat. Two people can eat the same diet and have very different results based on their genetic makeup.

Other genes in the study pointed to bile acids — the digestive chemicals your liver makes to help break down fats — and to the nerve signals that coordinate gut muscle contractions. The study also identified over 800 existing drug compounds that could potentially influence gut speed, opening the door to repurposing treatments that are already approved for other conditions.

Why Thiamine (Vitamin B1) Is a Particularly Interesting Clue for hEDS

Here's where things get really interesting for those of us in the hEDS world — and why this study is more than just an interesting footnote about bowel habits.

Vitamin B1 — also called thiamine — is something your nerves absolutely depend on. Without enough of it, the nervous system starts to malfunction. Here is why that matters for your gut: your digestive tract has its own private nervous system built right into its walls, sometimes called the 'gut brain.' It controls the wave-like muscle contractions (called peristalsis) that move food along. Your vagus nerve — the long nerve that runs from your brain all the way down to your abdomen — also helps regulate this process. Both systems rely on a chemical messenger called acetylcholine, and vitamin B1 is essential for making it. Less B1 means less acetylcholine, which means the gut's signals get quieter, slower, and less coordinated.

For someone with hEDS, this is a problem stacked on top of other problems. Many hEDS patients already have a nervous system that doesn't regulate itself well, that's part of what POTS is. Some have damage to the tiny nerve fibers in their skin and organs (called small fiber neuropathy), which further disrupts the signals that keep the gut moving. So imagine if, on top of all that, your genes also make it harder to get enough vitamin B1 into the cells that need it. Even a small reduction in efficiency could have real, noticeable effects on how your gut functions day to day.

THE POTS CONNECTION

POTS, which affects a large number of people with hEDS, is a condition where the nervous system struggles to regulate basic functions like heart rate and blood pressure when you stand up. That same nervous system also controls your gut. Vitamin B1 plays a role in keeping that system running smoothly. So when this study points to B1 metabolism as a gut-motility regulator, it may be especially relevant for hEDS patients who also have POTS.

The Broader Pattern: Gut Problems in hEDS Aren't One Thing

It would be easy to read this and think: 'Great, I'll just take a B1 supplement and fix my gut.' We wish it were that simple. The research isn't there yet to make that recommendation, scientists need to do more studies to understand exactly how this plays out in real patients before doctors can responsibly advise on it. But what the study does confirm is something hEDS patients have long suspected: the gut problems that come with this condition are not simple, they are not all in your head, and they do not come from one single cause.

The study also found strong genetic links between gut speed and conditions like anxiety and depression, which many hEDS patients also experience. This is not saying that gut problems cause anxiety, or vice versa. It's saying that the same underlying biology may contribute to both. The gut and the brain are deeply connected, and in hEDS, both systems are under stress. These genetic findings confirm that this gut-brain connection is real and measurable, not something doctors should be waving away.

The most common gut pattern seen in hEDS is the constipation-dominant form of IBS, meaning the gut moves too slowly, things get backed up, and bloating and discomfort follow. If vitamin B1 metabolism genuinely influences how fast the colon moves, and if some hEDS patients carry genes that make it harder to process B1 efficiently, we may be looking at a real, concrete reason why so many people in this community struggle with exactly this problem.

What This Means for You Right Now

We are not at the point where doctors can hand you a treatment plan based on this study alone, more research is needed first. But there are some reasonable, evidence-informed conversations you can start having with your doctor now:

Ask about formal gut motility testing

How often you go to the bathroom is only part of the picture. Tests like a gastric emptying study or a colon transit study can show exactly where in your digestive system things are slowing down, and that matters a lot for figuring out what kind of treatment might actually help.

Ask about having your vitamin B1 levels checked

Standard blood tests don't always catch low B1 accurately. A better test looks at how your red blood cells are using it (called erythrocyte transketolase activity) or measures it in whole blood. If you have constipation, POTS, and fatigue, this is worth bringing up with your doctor.

Think of it like the MTHFR conversation

Many people in the hEDS community have heard of MTHFR — a gene that affects how your body processes folate (a B vitamin), sometimes requiring a special 'activated' form. The B1 findings in this study work the same way: some people have genes that make it harder to absorb or activate a B vitamin, with real downstream effects on how their nervous system functions.

Bile acids may also be part of your picture

Another gene in the study connects to bile acids — the digestive fluids your liver makes to help break down food. In some people, bile acid imbalances contribute to constipation or diarrhea. This is already a treatment target in some IBS patients, and it may be relevant for some people with hEDS too.

The Bigger Picture

For years, people with hEDS have had to fight just to have their gut symptoms acknowledged. 'It's just IBS' has been used as a way to end the conversation rather than start a real investigation. This study, and the growing body of research behind it, is part of a scientific shift that is changing that, one discovery at a time.

When scientists can point to 21 specific locations in the human genome that influence gut speed, trace one of them directly to vitamin B1, and identify hundreds of potential drug targets, they are giving the hEDS community something it has always deserved: a scientific foundation that says your gut problems are real, they have identifiable causes, and they are worth investigating seriously.

It is real. It has a biology. And that biology is beginning to yield its secrets.

This article is for informational and educational purposes only and does not constitute medical advice. Always discuss any changes to your care plan with your treating physician.

Evidence-based insights for patients and clinicians navigating hypermobile EDS and related connective tissue disorders.

JONATHAN KOST, MD · JUNE 2026