Tulane University Study Links Folate Deficiency to Hypermobility Disorders

Hypermobility can manifest as overly flexible joints, leading to a range of symptoms beyond mere physical flexibility. Individuals with hypermobile EDS can experience joint pain, chronic fatigue, thin enamel, dizziness, digestive issues, and even psychiatric conditions like anxiety and depression. Women diagnosed with hypermobile EDS may face additional risks such as endometriosis or uterine fibroids.

Despite the high prevalence of hypermobile EDS—comprising over 90% of EDS cases—its underlying cause has been elusive. Previous research had not established a genetic correlate for this subtype, resulting in treatments that often address individual symptoms rather than the underlying cause. Tulane's findings could change this approach.

The study indicates that individuals with a specific genetic variant of the MTHFR gene are unable to effectively metabolize folate, leading to its accumulation in the bloodstream. This deficiency may hinder the ability of key proteins to bind collagen to the extracellular matrix, resulting in more elastic connective tissue and increased hypermobility.

Dr. Gregory Bix, director of the Tulane University Clinical Neuroscience Research Center, emphasized the significance of this discovery, stating, "You’ve got millions of people that likely have this, and until now, there’s been no known cause we’ve known to treat. It's a big deal."

This discovery could enable physicians to diagnose hypermobility and hypermobile EDS more accurately by testing for elevated folate levels and the MTHFR genetic variant. Dr. Jacques Courseault, medical director of the Tulane Fascia Institute, expressed optimism about the potential for improved treatment, stating, "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."

Historically, diagnosing hypermobility relied on the Beighton score, a physical exam that measures joint flexibility, which has faced scrutiny. The exact prevalence of hypermobility remains uncertain, though Courseault argues it could affect over half the global population. He likened hypermobility to a high-maintenance vehicle, underscoring the importance of recognizing different body types for effective treatment.

The Tulane research team uncovered the folate deficiency link while working with patients at the Hypermobility and Ehlers-Danlos Clinic, the only U.S. clinic focused on fascia disorders. Blood tests indicated elevated levels of unmetabolized folate in hypermobile patients, and most with these elevated levels also possessed the MTHFR genetic variant.

Fortunately, a treatment exists. Methylated folate, which is already processed and FDA-approved, is widely available. Dr. Bix noted, "It’s an innocuous treatment... We know what’s going on here, and we can treat it."

Although further research is needed, Courseault reported positive outcomes in treated patients, including reduced pain and improved gastrointestinal function. He concluded that the findings have the potential to benefit a large population globally, stating, "This is real, it’s been vetted out well and clinically we’re noticing a difference."