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Folate-dependent hypermobility syndrome: A proposed mechanism and diagnosis

Discussion in 'Fibromyalgia and Connective Tissue Disorders' started by vsou, Apr 22, 2023.

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  1. vsou

    vsou Established Member (Voting Rights)

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    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.
     
  2. Hutan

    Hutan Moderator Staff Member

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    Aotearoa New Zealand
    OK, I'll have a go.
    I can't comment on the credibility of the hypothesis - for me to unpick that would take a lot of time.

    For what it is worth: My folate levels are unremarkable, not elevated as this team suggest many people with hypermobility are (and I would qualify as 'hyper mobile'). The suggestion up front that 57% of people can suffer from hypermobility doesn't help with credibility.

    I think if 5-methyltetrahydrofolate had a substantial impact on ME/CFS-like symptoms, we would probably know by now, as it's a commercially available supplement. It's possible that it could have an effect on something like fascia structure where effects of supplementation would presumably take a longer time to be apparent.

    I thought the images of fascia thickness and disorganisation and the anecdotes of people with hyper mobility identifying areas of pain which were found to have thicker and disorganised fascia were interesting. There might be considerable scope for subjectivity in labelling images of fascia as having a problematic structure, so I hope the researchers blind the rating of images in any study involving such images.

    I couldn't find any obvious conflict of interests, other than the paper might act as an advertisement for the clinic that most of the authors are associated with. I liked that they were able to suggest studies that could help confirm or disprove their ideas, and hope that such studies are done.
     
    Peter Trewhitt, alktipping and Trish like this.
  3. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    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.
     
    RedFox, Peter Trewhitt, obeat and 4 others like this.
  4. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    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?
     
    Peter Trewhitt and alktipping like this.
  5. Amw66

    Amw66 Senior Member (Voting Rights)

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    May be epigenetic. GWAS didn't deal.in epigenetics
     
  6. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    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"].
     
    Last edited: Apr 23, 2023
    alktipping and Peter Trewhitt like this.
  7. ukxmrv

    ukxmrv Senior Member (Voting Rights)

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    854
    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.
     
    alktipping and Peter Trewhitt like this.
  8. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    The authors of the 'review' run the 'Fascia Institute and Treatment Centre'
    Presumably they are trying to bolster their supplement sales.
     
  9. FMMM1

    FMMM1 Senior Member (Voting Rights)

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

    Sid Senior Member (Voting Rights)

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    1,057
    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.
     

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