How Realistic Is a Possible Treatment for Hypermobile EDS?

By Crystal Lindell, PNN Columnist

Ever since I was diagnosed with hypermobile Ehlers-Danlos Syndrome (hEDS) back in 2018, I’ve spent countless hours contemplating what my life would be like if there was an effective treatment.

Last week, Tulane University School of Medicine pushed that question to the forefront. They announced that they may have found a potential cause of hEDS and hypermobility in general. They also theorized a potential treatment.

Ehlers-Danlos Syndrome (EDS) creates fragile connective tissue, which can cause a range of other symptoms including joint pain, digestive trouble, migraines and more.  

Tulane researchers proposed that a variation of the MTHFR gene that causes a deficiency of folate – the natural form of vitamin B9 – could hold the key to hypermobility and a range of connective tissue disorders such as EDS. As for treatment, they hypothesized that methylated folate — which is folate that is already processed — could be a possible treatment for the myofascial pain that’s common for hypermobile patients. They published these preliminary findings in the journal Heliyon.

First, it should be noted that none of this was based on a clinical study of patients. Rather, it’s a proposal that they believe should be researched further. As such, there’s been some valid criticism of Tulane’s announcement from the EDS community. Was it premature? Will any of this hold up in a peer-reviewed study? Or are they just giving false hope to the thousands of EDS patients desperate for some good news?

As an EDS patient myself, I understand those concerns and I very much sympathize with them. Many of us have spent too much time being dismissed by doctors, and too much money on treatments that don’t end up working.

Unfortunately, I think we’re going to have to live in the uncertainty right now. We won’t know if this is a viable option until we get a peer-reviewed study. But I am glad that they are looking into this and sharing these types of updates as the research progresses. I’d rather be informed along the way than only be told at the end of the process.

What Would a Treatment Mean for Patients?

What if their theory is correct though? Is that a good thing? I have to confess, my feelings about it are complicated.

The thing about EDS is that it’s different for everyone. As it stands, most doctors treat the symptoms, which, as mentioned above, vary widely. For me, the most debilitating one is intercostal neuralgia — which is not a type of myofascial pain. As such, it seems unlikely that methylated folate would do much to treat it.

But hey, maybe methylated folate is more of a preventative treatment? That alone would be an incredible advancement for hEDS patients.

The question is, would this treatment impact anything else? Do they know if it would only address myofascial pain? Or could it also help with other symptoms? And would that even be a good thing if it did?

EDS touches every aspect of my body and even most aspects of my personality. There’s the velvety skin everyone comments on when they shake my hand. And the constant comments about how I look for my age, which also seems to be related to how EDS impacts my skin. Would methylated folate treatment change that at all? How so? And what would I end up looking like?

The most well-known EDS symptom is probably loose joints, which means they easily overextend. For me, that’s meant a lifetime of sprained ankles and joint pain. But again, what happens if methylated folate changes that? My joints may be loose, but they’re the only ones I’ve ever known. Would stiffening them up actually help me at this point? Or would I have to re-learn how to move my own body?

What about my mind? EDS patients have higher than average rates of neurodivergence like autism and ADHD. They also have higher rates of mental health issues like depression and anxiety. Could this treatment change our brains too? Or, if not, what if they eventually find a treatment that does? Would it alter aspects of people’s personalities?

There’s also the more logistical issue of EDS as a name at all. According to the National Library of Medicine, a syndrome refers to a group of symptoms and physical findings without a direct cause. Once a cause is found, the symptoms are typically renamed as a “disease.” So, if the researchers at Tulane did find a cause, what do we have? Ehlers-Danlos disease? EDD?

One thing we do know is that EDS and hypermobility cause immeasurable pain and suffering for a lot of people, so we do need more research into potential treatments. Time will tell if folate treatment proves effective or not, but either way, I hope that there are a lot more potential treatments coming.

Crystal Lindell is a freelance writer who lives in Illinois. After five years of unexplained rib pain, Crystal was finally diagnosed with hypermobile Ehlers-Danlos syndrome. She and her fiancé have 3 cats: Princess Dee, Basil, and Goose. She enjoys the Marvel Cinematic Universe, Taylor Swift Easter eggs, and playing the daily word game Semantle. 

Researchers Find Possible Cause of Hypermobile EDS

By Crystal Lindell, PNN Columnist

Do we finally have a genetic link for hypermobile Ehlers-Danlos syndrome?

Researchers at Tulane University School of Medicine think so – and it could even point to an effective treatment that’s already available.

A variation of the MTHFR gene that causes a deficiency of folate – the natural form of vitamin B9 – could hold the key to hypermobility and a range of associated connective tissue disorders such as Ehlers-Danlos (EDS), according to preliminary findings published in the journal Heliyon.

“You’ve got millions of people that likely have this, and until now, there’s been no known cause we’ve known to treat,” said Gregory Bix, MD, director of the Tulane University Clinical Neuroscience Research Center. “It’s a big deal.”

People with the genetic variant can’t metabolize folate, which causes unmetabolized folate to accumulate in the bloodstream. The resulting folate deficiency in other parts of the body prevents key proteins from binding collagen to the extracellular matrix, which plays an important role in cell growth. This leads to more elastic connective tissue, hypermobility, and a potential cascade of associated conditions, researchers said.

The discovery could help doctors more accurately diagnose hypermobility and hypermobile EDS by looking for elevated folate levels in blood tests and the MTHFR genetic variant.

“Hypermobility is widespread and unfortunately under-recognized,” said Jacques Courseault, MD, medical director of the Tulane Fascia Institute and Treatment Center. “I’m excited about being able to treat the masses where people aren’t going their whole lives being frustrated and not getting the treatment they need."

Doctors discovered the connection between folate deficiency and the MTHFR gene by working with patients at Tulane’s Hypermobility and Ehlers-Danlos Clinic, the only clinic in the U.S. that focuses on fascia disorders. Blood tests of hypermobile patients revealed elevated levels of unmetabolized folate. Subsequent tests showed that most of those with elevated folate serum levels had the MTHFR genetic variant.

The good news is a treatment already exists. Methylated folate – folate that is already processed – is FDA-approved and widely available.

“It’s an innocuous treatment,” Bix said. “It’s not dangerous, and it’s a vitamin that can improve people’s lives. That’s the biggest thing: We know what’s going on here, and we can treat it.”

“We’ve discovered something in medicine that can help, not a small group of people, but potentially many across the world.”

— Dr. Jacques Courseault

Though more studies and clinical testing needs to be done, researchers say patients who have been treated with folate have shown improvement: less pain, less brain fog, fewer allergies and improved gastrointestinal function.

“We’ve discovered something in medicine that can help, not a small group of people, but potentially many across the world,” Courseault said. “This is real, it’s been vetted out well and clinically we’re noticing a difference.”

What Is Hypermobile EDS?

For those with hypermobile Ehlers-Danlos syndrome (EDS), the same conditions that create fragile connective tissue can cause a range of other symptoms that, on the surface, can seem unrelated: joint pain, chronic fatigue, thin tooth enamel, dizziness, digestive trouble and migraines, as well as psychiatric disorders such as anxiety and depression. Women with hypermobile EDS may also be at increased risk for endometriosis or uterine fibroids.

For years, researchers have struggled to find the cause of hypermobility and hypermobile EDS. Of the 13 subtypes of EDS, hypermobile EDS comprises more than 90 percent of cases. But until this study, hypermobile EDS was the only subtype without a known genetic correlate. As a result, symptoms have often been treated individually, without EDS being recognized as the likely cause.

Until now, hypermobility could only be diagnosed by the Beighton score, a somewhat controversial physical exam that involves measuring the bend of the spine, fingers and limbs. There has also been a historic lack of acceptance of hypermobility as a disorder that requires specialized treatment.

Many patients with hypermobile EDS never get a proper diagnosis. As a result, the number of people with hypermobility is unclear, though it could comprise more than half the world’s population.

“Hypermobility is not rare,” Courseault said. “Hypermobility is like a Ferrari that requires a lot of maintenance and the best synthetic oil. After knowing a patient's name and date of birth, I think it's prudent for clinicians to know which of these body types they have.”

Crystal Lindell is a freelance writer who lives in Illinois. After five years of unexplained rib pain, Crystal was finally diagnosed with hypermobile Ehlers-Danlos syndrome. She and her fiancé have 3 cats: Princess Dee, Basil, and Goose. She enjoys the Marvel Cinematic Universe, Taylor Swift Easter eggs, and playing the daily word game Semantle.