Prof. Martin Pall and active forms of folate

Discussion in 'Fibromyalgia Main Forum' started by richvank, Mar 22, 2009.

  1. richvank

    richvank New Member

    Hi, all.

    As many of you know, Prof. Martin Pall and I have both proposed hypotheses for
    the pathogenesis of CFS. Marty's is based on a vicious circle mechanism
    involving nitric oxide and peroxynitrite. I have adopted a methylation-based
    hypothesis that came from work in autism, and is very similar to the autism
    pathogenesis hypothesis that has been published by Prof. Richard Deth et al.

    The treatments Marty and I have suggested, based on our respective pathogenesis
    hypotheses, have had some similarities. Marty's has emphasized antioxidants and
    substances believed to lower nitric oxide or peroxynitrite. His protocol has
    included hydroxocobalamin and folic acid.

    Based on the full treatment program of Dr. Amy Yasko in autism, I have
    emphasized use of hydroxocobalamin together with active forms of folate, i.e.
    5-methyl tetrahydrofolate (aka 5-MTHF, FolaPro or Metafolin) and folinic acid,
    in order to stimulate the activity of the enzyme methionine synthase, which I
    believe is partially blocked in CFS, and which I believe constitutes the basic
    biochemical problem in this disorder.

    I have had a few conversations and several email interactions with Marty over
    the past couple of years, and I have encouraged him to try the active forms of
    folate, rather than folic acid, but he has not been willing to do that, because
    he could not justify it on the basis of his hypothesis.

    Well, now it appears that this is changing. Marty has now found, based on a
    paper published in 2006 by Antoniades et al., that 5-methyltetrahydrofolate is a
    scavenger for peroxynitrite, and he has therefore started to entertain the idea
    of boosting it. He has suggested doing so by using serine supplementation,
    since serine normally is one of the substrates for 5-MTHF. However, building
    5-MTHF this way is subject to having a supply of THF, which we have measured to
    be low in many PWCs, and it also depends on reactions catalyzed by SHMT and
    MTHFR, either or both of which may have polymorphisms. So I still prefer the
    direct supplementation of 5-MTHF, for these reasons.

    Marty has also mentioned that folinic acid may be helpful.

    He and I will no doubt continue to explore and debate the theoretical
    biochemical underpinnings, but I'm happy to see this movement toward
    consideration of more active forms of folate, because he has quite a following
    of people trying his protocol, and based on the Nathan clinical study and the
    mounting number of reports on cfs-yasko and the prohealth CFS board from people
    who are benefiting from the simplified treatment approach, I'm convinced that
    the PWCs who are following Marty's protocol would benefit from moving toward
    more active forms of folate, since it appears that many PWCs are not able to
    make effective use of folic acid. If Marty continues to move in this direction,
    these PWCs will be able to start benefiting from a treatment that has been shown
    to work well, even though he and I still may not have settled on a theoretical
    explanation that we can agree upon.