Folate-dependent hypermobility syndrome: A proposed mechanism and diagnosis

Looking for views on this study

https://www.cell.com/heliyon/fulltext/S2405-8440(23)02594-X


Abstract
Hypermobility involves excessive flexibility and systemic manifestations of connective tissue fragility. We propose a folate-dependent hypermobility syndrome model based on clinical observations, and through a review of existing literature, we raise the possibility that hypermobility presentation may be dependent on folate status. In our model, decreased methylenetetrahydrofolate reductase (MTHFR) activity disrupts the regulation of the ECM-specific proteinase matrix metalloproteinase 2 (MMP-2), leading to high levels of MMP-2 and elevated MMP-2-mediated cleavage of the proteoglycan decorin. Cleavage of decorin leads ultimately to extracellular matrix (ECM) disorganization and increased fibrosis. This review aims to describe relationships between folate metabolism and key proteins in the ECM that can further explain the signs and symptoms associated with hypermobility, along with possible treatment with 5-methyltetrahydrofolate supplementation.

 

It looks like the usual quackery.
If 57% of people have hypermobility then it is very normal.
The stuff about metalloproteinases is nonsense. You would need to destroy collagen to get hypermobility - and pretty much all of it since even a few threads will be non-distensible.
I have no idea whether or not this is in any sense a real journal. Nobody seems to care any more.

 

Too much to ask that anyone actually measured anything --- if "5-methyltetrahydrofolate" was actually relevant then I guess it would turn up on GWAS --- if they're [scientists, Doctors, patients] persuaded then why not do a large GWAS study?

 

May be epigenetic. GWAS didn't deal.in epigenetics

 

My "knowledge" is very limited but I think GWAS studies can still turn up research/treatment targets. I think you may be confusing:

• "pure"/"simple" genetic diseases like haemophilia - GWAS "solves" those;
• with diseases with genetic predisposition/where environmental factors are relevant - GWAS may still allow you to target your research -- genes, pathways ---

If you look at the:

• recent breakthrough in MS (EBV) then GWAS would tell you that certain immune genes are involved in MS. Potentially indicating triggering pathogen/environmental trigger;
• GWAS in migraine identified the gene/pathway which is targeted in the currently treatable form [50%];

Useful clues I assume i.e. in targeting research/treatments.

I think the greater barriers are:

• GWAS is expensive;
• heterogeneous population dementia has required large GWAS studies i.e. to identify genes. Environmental factors are presumably important but but [EDIT - post GWAS the "hope" is that they can focus research to find those - delete "may be difficult to identify those"].

 

There was an interest in MTHFR back in the days of the Pheonix Rising website back to 2009 and it was also discussed on the old Experimental yahoo group.

Been such a long time with little to show in even anecdotal reports.

 

The authors of the 'review' run the 'Fascia Institute and Treatment Centre'
Presumably they are trying to bolster their supplement sales.

 

Yea slightly tongue in cheek i.e. referring to GWAS --- seems no one is really interested in doing research.

 

MTHFR is such a blast from the past. There was a time about 10-15 years ago when it purported to be the explanation for everything in alternative medical circles. Half the population have the “mutation”. I am amazed anyone actually sat down and typed all this nonsense in 2023.