Low creatine? Does this ring a bell anyone?

Discussion in 'Fibromyalgia Main Forum' started by deliarose, Mar 19, 2007.

  1. deliarose

    deliarose New Member

    I was tidying up my inbox, and came across this old post from Rich Van Konyenburg on teh CFSFMexperimental list.

    If I understand it correctly, it may explain why some of us have low creatine readings. My PCP brushed this off, but it was one of the few abnormal markers I had.

    Needless to say my PCP has no business treating people with CFS. He is clueless, although he freely admits he is just treating the symptoms without understanding the underlying causes.

    And my doc is an adviser to the CDC!Ha.

    Hi, all.

    One more interesting connection has popped up in my study of what
    happens if there is decreased capacity for methylation in CFS, as
    would occur if the glutathione depletion--methylat ion cycle block
    hypothesis for the pathogenesis of CFS is valid.

    Some of you may know that there have been four studies involving MRS
    (magnetic resonance spectroscopy) , which is not the same as MRI
    (magnetic resonance imaging), in CFS. As an aside, you may know
    that MRI shows "white spots" in the brain in CFS, and Dr. Cheney has
    suggested that they are caused by ministrokes, resulting from
    the "hole in the heart" he is finding in many PWCs. I think he is
    probably right about that.

    But getting back to MRS, these studies have reported that the ratio
    of choline to creatine is elevated in various parts of the brain.
    Dr. Cheney has collaborated with Dr. Susan Levine and some people at
    Columbia University to do this kind of study, and there have been
    studies from Japan and the U.K. as well. You may wonder why they
    chose to measure the levels of these particular substances, and why
    they express the results as a ratio. Well, this is a technique-
    driven study. One of the available ways to scan the brain is to use
    proton magnetic resonance spectroscopy. If you do proton MRS on a
    person's brain with the field strength of superconducting magnets
    that are available commercially, only a few substnces will produce
    observable peaks in the spectrum, and whatever substances produce
    peaks are the ones you have to work with. Two of them are choline
    and creatine, so whether or not these are your favorite biochemical
    substances, they are what you get from this technique, and you try
    to infer whatever you can from their levels. Also, it isn't easy to
    do an absolute measurement of the amount of something using magnetic
    resonance. It's much easier to just take ratios of the peak heights
    that you get, and that's why the results are given as ratios of
    substances that may not really have much to do with each other in
    terms of their biochemical function or pathways. Anyway, that's why
    they report what they report from MRS.

    Now, most of the time, creatine is viewed as being present at a
    constant concentration, becuase in most disorders, it doesn't vary
    much. (This same reason is why creatinine, which is produced
    nonenzymatically from the breakdown of creatine at a fairly constant
    breakdown rate, is usually viewed as being relatively constant in
    urine testing, so that other substances are ratioed to it in order
    to correct for more or less water in the urine, depending on how
    much the person drank and/or sweated. However, people with autism
    and CFS are finding that the urine creatinine levels do move around,
    and that these changes are important. But I digress.)

    So, back to the MRS studies. Since creatine is usually viewed as
    constant, the researchers have suspected that the high choline to
    creatine ratio means that for some reason choline is high in the
    parts of the brain that were studied. In one study, they also
    ratioed the choline peak to the water peak, and this ratio was high,
    too, giving more support to the high-choline interpretation.
    (However, bear in mind that this is still a ratio, and if for some
    reason the brain was dehydrated, this ratio would come out high,
    too, so you still can't be sure that choline has risen in absolute
    terms from this type of measurement. )

    Why am I writing about all of this? Well, it is a fact that both
    creatine and choline are partly synthesized in the body, and partly
    come from the diet. Furthermore, it is a fact that methylation
    reactions are needed to make both creatine and choline in the body.
    In fact, it has been found that 70 to 75% of the total methylation
    capacity of S-adenosylmethionin e (SAMe) is used to make creatine.
    It has also been found that the conversion of ethanolamine to
    choline is perhaps the second biggest user of methylation (each
    molecule requires three methylations) . So this means that the
    levels of both creatine and choline would be diminished in the body
    of a person with CFS. Now, since the MRS studies only evaluate
    ratios, they won't show the drops in absolute amounts of creatine
    and choline. But the ratio is bound to be disturbed if the
    methylation capacity drops, because it would take an amazing
    coincidence for the production of both to be decreased exactly
    proportionately when the methylation capacity goes down. If this
    hypothesis is indeed valid in CFS, the increase in the ratio of
    choline to creatine observed in these studies would mean that the
    inventory of creatine in the brain is being decreased more by the
    methylation deficit than is the inventory of choline. That is, both
    inventories have dropped, but the amount of creatine has dropped by
    a larger fractional amounts.

    So what's the significance of this? Well, I think it gives more
    support for the overall pathogenesis hypothesis, and it also
    explains an observation that has been well supported by four
    clinical studies, but has never been explained before now. Add this
    to the other phenomena that have never been explained, but which are
    explained by this hypothesis, and I hope this hypothesis is
    beginning to sound more interesting.

    Now I know you are all interested in treatment, and some benefit can
    be gotten by supplementing creatine and choline (the latter perhaps
    as phosphatidylcholine , as is done by the NT Factor treatment being
    advocated by Dr. Garth Nicolson, as well as by the I.V. infusions of
    phosphatidylcholine that are part of the protocol advocated by Dr.
    Patricia Kane), but I would emphasize that according to this
    hypothesis the more fundamental issue is to fix the methylation
    cycle block, because that is the root cause for not only the choline
    and creatine deficits, but for a whole lot more. Unless we deal
    with root causes, I don't think we will have cures. I know we're
    not supposed to discuss the Yasko treatment approach here, but I
    would reiterate that so far I think that her approach is the best
    for dealing with the methylation cycle block. If people want to
    discuss that, please do it on the Yasko_cfs group:
    http://health. groups.yahoo. com/group/ CFS_Yasko/

    Rich