Normal NK Cells - CFS not active?

Discussion in 'Fibromyalgia Main Forum' started by shell, Mar 2, 2009.

  1. shell

    shell New Member

    OK so I finally finally got my NK cells tested.... they came out right in the middle of normal, which is great, but my doctor now thinks if I do have CFS that it is not in an 'active' state right now. I was so looking forward to some kind of advice or treatment, as having this for 7 years I kind of know I am in an 'active' state right now. My ebv and hhv6 came back high but 'unimpressive'.

    Back to the home remedies and treating myself. Anyone else have every symptom of CFS and know they are in an active state with normal NK cell? I have a call in today to find out if this covered the activity and the numbers but it was the 'assay' so I assume both.

    I felt really let down that the only doctor who I thought understood CFS now feels I am OK since this value came out good.

    Does anyone agree or disagree with his statement?

    UPDATE TALKED TO NURSE - was counts only not activity... now didn't I read somewhere that we can have normal counts and less activity?????

    Thanks!
    SHELL



    [This Message was Edited on 03/02/2009]
    [This Message was Edited on 03/02/2009]
  2. AuntTammie

    AuntTammie New Member

    sorry I don't have an answer except to say that our tests often appear to be "normal" for a lot of reasons even when we are obviously not ok

    that said, is it high or low NK cells that is supposed to be indicative of active CFS?

    I just had a lot of blood work done & am researching the results...my Dr said it all looks fine, when it actually states on the results that certain things are not in the normal range....my Dr doesn't know much of anything about cfs, though, and I am trying to find one who does
  3. wendysj

    wendysj New Member

    I'm definitely not an expert on blood work but I do know if there was one test to diagnose CFS we here would all know about it. My blood work came back "discustingly healthy" the last time I went to a GP... Not what I wanted to hear.

    My real doctor said the tests were normal but that doesn't mean I don't have FM/CFS.

    Hope you get some answers.
    Wendysj
  4. richvank

    richvank New Member

    Hi, wendysj and the group.

    If you seriously want to get a test panel that will tell you whether you have CFS (at least the kind that involves glutathione depletion and a partial block in the methylation cycle, which, so far, appears to be the majority of cases), then I would suggest that you ask your doctor to order the Methylation Pathways Panel from Vitamin Diagnostics, Inc. So now you know about it! Dr. Nathan and I are planning to report on the clinical study of methylation cycle treatment of patients with CFS and FM at the IACFS/ME Conference in Reno the weekend after next. This study made use of this panel repeatedly on the same set of patients, over a 6-month treatment period, and the results are very positive. I wouldn't be surprised if the demand for this panel became greater after the conference. The lab in New Jersey, as well as the parent lab in the Netherlands, are already having to hire more analytical chemists to handle the samples that are coming in. They have also just opened a branch office in Spain because of the demand there. And by the way, I have no financial connection to these labs.

    Rich

    Here's the information:

    Methylation Pathways Panel

    This panel will indicate whether a person has a partial methylation cycle block and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block. I am not associated with the lab that offers this panel.

    The panel costs $300 and requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on your clinician’s letterhead.


    Available from:

    Vitamin Diagnostics, Inc.
    Rt. 35 & Industrial Drive
    Cliffwood Beach, NJ 07735
    USA
    Phone:+1 (732) 583-7773
    Fax: +1 (732) 583-7774)



    Here is some detailed information about the test panel and how to interpret the results:

    Several people have asked for help in interpreting the results of
    their Vitamin Diagnostics, Inc., methylation pathway panels. Here are my
    suggestions for doing so. They are based on my study of the
    biochemistry involved, on my own experience with interpreting more
    than 120 of these panel results to date, and on discussion of some of
    the issues with Tapan Audhya, Ph.D., who is the director of the
    Vitamin Diagnostics lab.

    The panel consists of measurement of two forms of glutathione
    (reduced and oxidized), adenosine, S-adenosylmethionine (SAM) , S-
    adenosylhomocysteine (SAH), and seven folic acid derivatives or
    vitamers.

    According to Dr. Audha, the reference ranges for each of these
    metabolites was derived from measurements on at least 120 healthy
    male and female volunteer medical students from ages 20 to 40, non-
    smoking, and with no known chronic diseases. The reference ranges
    extend to plus and minus two standard deviations from the mean of
    these measurements.

    Glutathione: This is a measurement of the concentration of the
    reduced (active) form of glutathione (abbreviated GSH) in the blood
    plasma. From what I've seen, most people with chronic fatigue
    syndrome (PWCs) have values below the reference range. This means
    that they are suffering from glutathione depletion. As they undergo
    the simplified treatment approach to lift the methylation cycle
    block, this value usually rises into the normal range over a period
    of months. I believe that this is very important, because if
    glutathione is low, vitamin B12 is unprotected and reacts with toxins
    that build up in the absence of sufficient glutathione to take them
    out. Vitamin B12 is thus hijacked, and not enough of it is able to
    convert to methylcobalamin, which is what the methylation cycle needs
    in order to function normally. Also, many of the abnormalities and
    symptoms in CFS can be traced directly to glutathione depletion.

    Glutathione (oxidized): This is a measurement of the concentration
    of the oxidized form of glutathione (abbreviated GSSG) in the blood
    plasma. In many (but not all) PWCs, it is elevated above the normal
    range, and this represents oxidative stress.

    Adenosine: This is a measure of the concentration of adenosine in the
    blood plasma. Adenosine is a product of the reaction that converts
    SAH to homocysteine. In some PWCs it is high, in some it is low, and
    in some it is in the reference range. I don't yet understand what
    controls the adenosine level, and I suspect there are more than one
    factor involved. In most PWCs who started with abnormal values, the
    adenosine level appears to be moving into the reference range with
    methylation cycle treatment, but more data are needed.

    S-adenosymethionine (RBC) (SAM): This is a measure of the
    concentration of SAM in the red blood cells. Most PWCs have values
    below the reference range, and treatment raises the value. S-
    adenosylmethionine is the main supplier of methyl groups in the body,
    and hundreds of biochemical reactions depend on it for their methyl
    groups. A low value for SAM represents low methylation capacity, and
    it usually results from a partial block at the enzyme methionine
    synthase. Many of the abnormalities in CFS result from lack of
    sufficient methyation capacity.

    S-adenosylhomocysteine (RBC) (SAH): This is a measure of the
    concentration of SAH in the red blood cells. In CFS, its value
    ranges from below the reference range, to within the reference range,
    to above the reference range. Values appear to be converging toward
    the reference range with treatment. SAH is the product of reactions
    in which SAM donates methyl groups to other molecules.

    Sum of SAM and SAH: When the sum of SAM and SAH is below 268
    micromoles per deciliter, it appears to suggest the presence of
    upregulating polymorphisms in the cystathione beta synthase (CBS)
    enzyme, though this may not be true in every case.

    Ratio of SAM to SAH: A ratio less than about 4.5 also represents low
    methylation capacity. Both the concentration of SAM and the ratio of
    concentrations of SAM to SAH are important in determining the
    methylation capacity.

    5-CH3-THF: This is a measure of the concentration of 5-methyl
    tetrahydrofolate in the blood plasma. It is normally the most
    abundant form of folate in the blood plasma. It is the form that
    serves as a reactant for the enzyme methionine synthase, and is thus
    the most important form for the methylation cycle. Most PWCs have a
    low value, consistent with a partial block in the methylation cycle.
    The simplified treatment approach includes FolaPro, which is
    commercially produced 5-CH3-THF, so that when this treatment is used,
    this value rises in nearly every PWC. If the concentration of 5-CH3-
    THF is within the reference range, but either SAM or the ratio of SAM
    to SAH is below the reference values, it suggests that there is a
    partial methylation cycle block and that it is caused by
    unavailability of sufficient bioactive B12, rather than
    unavailability of sufficient folate. I have seen this frequently,
    and I think it demonstrates that the hijacking of B12 is the root
    cause of most cases of partial methylation cycle block. Usually
    glutathione is low in these cases, which is consistent with lack of
    protection for B12, as well as toxin buildup.

    10-Formyl-THF: This is a measure of the concentration of 10-formyl
    tetrahydrofolate in the blood plasma. It is usually low in PWCs.
    This form of folate is involved in reactions to form purines, which
    form part of RNA and DNA as well as ATP.

    5-Formyl-THF: This is a measure of the concentration of 5-formyl
    tetrahydrofolate (also called folinic acid) in the blood plasma.
    Most but not all PWCs have a low value. This form is not used
    directly as a substrate in one-carbon transfer reactions, but it can
    be converted into other forms of folate. It is one of the
    supplements in the simplified treatment approach, which helps to
    build up various other forms of folate.

    THF: This is a measure of the concentration of tetrahydrofolate in
    the blood plasma. It is lower than the mean normal value of 3.7
    nanomoles per liter in most but not all PWCs. This is the
    fundamental chemically reduced form of folate from which several
    other reduced folate forms are made. The supplement folic acid is
    converted into THF by two sequential reactions catalyzed by
    dihydrofolate reductase (DHFR). THF is also a product of the
    reaction of the methionine synthase enzyme, and it is a reactant in
    the reaction that converts formiminoglutamate (figlu) into
    glutamate. If figlu is high in the Genova Diagnostics Metabolic
    Analysis Profile, it indicates that THF is low.

    Folic acid: This is a measure of the concentration of folic acid in
    the blood plasma. Low values suggest folic acid deficiency in the
    current diet. High values are sometimes associated with inability to
    convert folic acid into other forms of folate, such as because of
    polymorphisms in the DHFR enzyme. They may also be due to high
    supplementation of folic acid.

    Folinic acid (WB): This is a measure of the concentration of folinic
    acid in the whole blood. See comments on 5-formyl-THF above. It
    usually tracks with the plasma 5-formyl-THF concentration.

    Folic acid (RBC): This is a measure of the concentration of folic
    acid in the red blood cells. The red blood cells import folic acid
    when they are initially being formed, but during most of their
    approximately four-month life, they do not import, export, or use
    it. They simply serve as reservoirs for it, giving it up when they
    are broken down. Many PWCs have low values. This can normally be
    caused by a low folic acid status in the diet over the previous few
    months, since the population of RBCs at any time has ages ranging
    from zero to about four months. However, in CFS it can also be
    caused by damage to the cell membranes, which allows folic acid to
    leak out of the cells. Dr. Audhya reports that treatment with omega-
    3 fatty acids can raise this value over time.


  5. goldiland

    goldiland New Member

    Rich,

    Have you ever heard of a product called maxGXL? It was designed by Dr. Robert Keller who previously worked with Klimas and the U of M team and is supposed to address methylation. I live in South Florida and am a patient of Klimas but am considering seeing Dr. Keller to address potential gluthathione. I have been on immunovir for about six months but am really not feeling a lot better and agree that the problem may be body's ability to detox even with immune modulator. My NK cells are going up (around 150) and activity has slightly increased (around 10%) but is still poor.

    Thanks,
    Gregg
  6. richvank

    richvank New Member

    Yes, I've heard of it, and in fact I have some and am taking it. I don't have CFS myself, and I'm taking it because a guy whose mother was helped by it and who sells it wanted very much for me to take it, to the point that he offered to buy me a month's worth. I turned that down, but agreed to buy a month's worth myself and take it. I didn't expect to experience much of a change, because I've taken most of the ingredients in the supplement on and off over the past few years, and in fact, I haven't noticed anything. But he is such a nice guy that I didn't want to disappoint him!

    I find it interesting that some of the people who are selling this product on the internet are actually quoting me on some things I've posted about glutathione over the past few years in their ads, but they have never contacted me! As long as they don't say that I'm endorsing the product, I guess it's O.K. It kind of surprised me to see that, though. They are also quoting Prof. Marty Pall, and I doubt whether they contacted him, either.

    I do think that glutathione is very important to the health of people in general, and I think that many people who do not have CFS would be helped by this type of product. I encouraged PWCs to take things like this over the period from 1999 to late 2004, and you can find an article about it written by me on the phoenix-cfs website. It helped quite a few PWCs temporarily, but if they stopped, it seemed that the glutathione levels dropped back down in nearly all of them. I reported on this at the 2004 IACFS conference. Shortly after that I read the paper by Jill James et al. in autism, and a light came on for me. I finally realized why we couldn't raise glutathione permanently in people with CFS. There is a partial block in the methylation cycle, which is upstream of glutathione synthesis in the sulfur metabolism. We have to fix that partial block, and when we do, we have found that glutathione just comes up naturally, without any direct support.

    I haven't heard from anyone with CFS who has tried this product, but I would be interested to hear from those who decide to try it. I'm not encouraging PWCs to try it, because if my experience means anything and my current hypothesis for CFS is correct, it won't be a permanent solution to the glutathione depletion in CFS, and it isn't cheap.

    It's interesting to hear of the connection with Nancy Klimas. I have been trying for a long time to get her to take seriously what we have been doing with glutathione and methylation. If she's actually getting interested in it, I'm very happy to hear that.

    In my hypothesis, all the problems that have been found with the immune system in CFS, includng those discovered by Nancy and her group, can be traced very specifically and in detail to the partial block in methionine synthase, which causes dysfunction of the methylation cycle and the folate metabolism, and is coupled to glutathione depletion in a vicious circle mechanism, and that's what makes CFS chronic.

    As an example, the problem of low NK cell activity has been raised in this thread. A few years ago, Kevin Maher, who used to be in Nancy's group, discovered that the NK cells in CFS do not produce enough perforin, which is what NK cells use to poke holes in the infected cells that they kill. I believe that that is what accounts for their low cytotoxic activity. The perforin molecule has twenty cysteine residues, which are connected together to form cystine disulfide bonds. It has been shown that if there is insufficient glutathione in cells that produce secretory proteins (which is what perforin is) that incorporate cystine disulfide bonds, these proteins will not be properly formed, because the cysteines will not be joined with their proper partners, and most of the protein molecules will be recycled via the proteosome. According to my hypothesis, that's what causes the low production of perforin by NK cells, and it's also what causes their low cytotoxic activity.

    There are also very specific biochemical mechanisms in this hypothesis that explain all the other observed immune dysfunctions in CFS. I presented this in a poster paper at the 2007 IACFS conference.

    I'm hopeful that I will be able to get through to some more of the CFS research and clinical community at the upcoming IACFS/ME conference in Reno the weekend after next. I'm planning to present a poster paper on the results of the recent clinical study that tested this hypothesis and treated to support the methylation cycle. The hypothesis came though with flying colors, and nearly all the patients reported at least some improvement, some experiencing a great deal of improvement.

    Rich
    [This Message was Edited on 03/02/2009]
  7. ladybugmandy

    ladybugmandy Member

    wonder if you can have RNase L tested?
  8. shell

    shell New Member

    who responded. I am feeling a little better now, just tired of being overlooked as having a problem :)

    I have analyzed it and I do believe that drinking green tea and kambucha tea everyday and eating loads of garlic have probably put me into a good 'average' category for NK cells.

    If that is the case I wish I felt better too! But glad to be into the average category anyways, I was expecting the worse from what I had read.

    Thanks for all the info ... I will be looking into these other tests...

    SHELL
  9. goldiland

    goldiland New Member

    Rich,

    I appreciate the response. Although I can't speak for all of the things Nancy is engaged in, I do know that she is actively pursuing CFS markers and genotypes. I am in a couple of her studies. At least with my case, she is very focused on NK markers and immunolgoical studies to guide treatment. I am definitely interested in the methylation theory and would like your input about the type of testing to get to see if this is a problem for me. Amy Yasko testing or Vitamin Co in NJ? I have had some amino acid/vitamin studies done and my folate acid and homeocysteine levels were in normal range. Not sure if these are always out of range in methylation cycle problem though. B12 was close to 300 with (200-1100) so was fairly low.

    Thanks,
    Gregg
  10. richvank

    richvank New Member

    Hi, Gregg.

    I would recommend getting the Vitamin Diagnostics methylation pathways panel, because it will give you a direct answer as to whether you have a partial methylation cycle block and/or glutathione depletion. Amy Yasko's nutrigenomic panel is helpful for those who want to follow her full treatment program.

    Conventional tests for folate, homocysteine and B12 will often not reveal that there is a partial methylation cycle block, which is part of the reason why the conventional physicians miss this problem. The other part is that the understanding of this problem is very new, and has not gotten to most of the physicians up to now. I'm hoping to improve that situation a little this weekend at the IACFS/ME conference, where we are reporting on our clinical study of the methylation cycle block treatment.

    Here's the contact data for the Vitamin Diagnostics panel:

    Methylation Pathways Panel

    This panel will indicate whether a person has a partial methylation cycle block and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block. I am not associated with the lab that offers this panel.

    The panel costs $300 and requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on your clinician’s letterhead.


    Available from:

    Vitamin Diagnostics, Inc.
    Rt. 35 & Industrial Drive
    Cliffwood Beach, NJ 07735
    USA
    Phone:+1 (732) 583-7773
    Fax: +1 (732) 583-7774)

    Lab Director: Tapan Audhya, Ph.D.
    (usually at the lab on Tues. and Wed. from 1 to 3 p.m., Eastern time)

    Dr. Audhya is willing to help clinicians with interpretation of the panel by phone.


    Here are some comments on the interpretation of this panel:

    Several people have asked for help in interpreting the results of
    their Vitamin Diagnostics, Inc., methylation pathway panels. Here are my
    suggestions for doing so. They are based on my study of the
    biochemistry involved, on my own experience with interpreting more
    than 120 of these panel results to date, and on discussion of some of
    the issues with Tapan Audhya, Ph.D., who is the director of the
    Vitamin Diagnostics lab.

    The panel consists of measurement of two forms of glutathione
    (reduced and oxidized), adenosine, S-adenosylmethionine (SAM) , S-
    adenosylhomocysteine (SAH), and seven folic acid derivatives or
    vitamers.

    According to Dr. Audha, the reference ranges for each of these
    metabolites was derived from measurements on at least 120 healthy
    male and female volunteer medical students from ages 20 to 40, non-
    smoking, and with no known chronic diseases. The reference ranges
    extend to plus and minus two standard deviations from the mean of
    these measurements.

    Glutathione: This is a measurement of the concentration of the
    reduced (active) form of glutathione (abbreviated GSH) in the blood
    plasma. From what I've seen, most people with chronic fatigue
    syndrome (PWCs) have values below the reference range. This means
    that they are suffering from glutathione depletion. As they undergo
    the simplified treatment approach to lift the methylation cycle
    block, this value usually rises into the normal range over a period
    of months. I believe that this is very important, because if
    glutathione is low, vitamin B12 is unprotected and reacts with toxins
    that build up in the absence of sufficient glutathione to take them
    out. Vitamin B12 is thus hijacked, and not enough of it is able to
    convert to methylcobalamin, which is what the methylation cycle needs
    in order to function normally. Also, many of the abnormalities and
    symptoms in CFS can be traced directly to glutathione depletion.

    Glutathione (oxidized): This is a measurement of the concentration
    of the oxidized form of glutathione (abbreviated GSSG) in the blood
    plasma. In many (but not all) PWCs, it is elevated above the normal
    range, and this represents oxidative stress.

    Adenosine: This is a measure of the concentration of adenosine in the
    blood plasma. Adenosine is a product of the reaction that converts
    SAH to homocysteine. In some PWCs it is high, in some it is low, and
    in some it is in the reference range. I don't yet understand what
    controls the adenosine level, and I suspect there is more than one
    factor involved. In most PWCs who started with abnormal values, the
    adenosine level appears to be moving into the reference range with
    methylation cycle treatment, but more data are needed.

    S-adenosymethionine (RBC) (SAM): This is a measure of the
    concentration of SAM in the red blood cells. Most PWCs have values
    below the reference range, and treatment raises the value. S-
    adenosylmethionine is the main supplier of methyl groups in the body,
    and hundreds of biochemical reactions depend on it for their methyl
    groups. A low value for SAM represents low methylation capacity, and
    it usually results from a partial block at the enzyme methionine
    synthase. Many of the abnormalities in CFS result from lack of
    sufficient methyation capacity.

    S-adenosylhomocysteine (RBC) (SAH): This is a measure of the
    concentration of SAH in the red blood cells. In CFS, its value
    ranges from below the reference range, to within the reference range,
    to above the reference range. Values appear to be converging toward
    the reference range with treatment. SAH is the product of reactions
    in which SAM donates methyl groups to other molecules.

    Sum of SAM and SAH: When the sum of SAM and SAH is below 268
    micromoles per deciliter, it appears to suggest the presence of
    upregulating polymorphisms in the cystathione beta synthase (CBS)
    enzyme, though this may not be true in every case.

    Ratio of SAM to SAH: A ratio less than about 4.5 also represents low
    methylation capacity. Both the concentration of SAM and the ratio of
    concentrations of SAM to SAH are important in determining the
    methylation capacity.

    5-CH3-THF: This is a measure of the concentration of 5-methyl
    tetrahydrofolate in the blood plasma. It is normally the most
    abundant form of folate in the blood plasma. It is the form that
    serves as a reactant for the enzyme methionine synthase, and is thus
    the most important form for the methylation cycle. Most PWCs have a
    low value, consistent with a partial block in the methylation cycle.
    The simplified treatment approach includes FolaPro, which is
    commercially produced 5-CH3-THF, so that when this treatment is used,
    this value rises in nearly every PWC. If the concentration of 5-CH3-
    THF is within the reference range, but either SAM or the ratio of SAM
    to SAH is below the reference values, it suggests that there is a
    partial methylation cycle block and that it is caused by
    unavailability of sufficient bioactive B12, rather than
    unavailability of sufficient folate. I have seen this frequently,
    and I think it demonstrates that the hijacking of B12 is the root
    cause of most cases of partial methylation cycle block. Usually
    glutathione is low in these cases, which is consistent with lack of
    protection for B12, as well as toxin buildup.

    10-Formyl-THF: This is a measure of the concentration of 10-formyl
    tetrahydrofolate in the blood plasma. It is usually low in PWCs.
    This form of folate is involved in reactions to form purines, which
    form part of RNA and DNA as well as ATP.

    5-Formyl-THF: This is a measure of the concentration of 5-formyl
    tetrahydrofolate (also called folinic acid) in the blood plasma.
    Most but not all PWCs have a low value. This form is not used
    directly as a substrate in one-carbon transfer reactions, but it can
    be converted into other forms of folate. It is one of the
    supplements in the simplified treatment approach, which helps to
    build up various other forms of folate.

    THF: This is a measure of the concentration of tetrahydrofolate in
    the blood plasma. It is lower than the mean normal value of 3.7
    nanomoles per liter in most but not all PWCs. This is the
    fundamental chemically reduced form of folate from which several
    other reduced folate forms are made. The supplement folic acid is
    converted into THF by two sequential reactions catalyzed by
    dihydrofolate reductase (DHFR). THF is also a product of the
    reaction of the methionine synthase enzyme, and it is a reactant in
    the reaction that converts formiminoglutamate (figlu) into
    glutamate. If figlu is high in the Genova Diagnostics Metabolic
    Analysis Profile, it indicates that THF is low.

    Folic acid: This is a measure of the concentration of folic acid in
    the blood plasma. Low values suggest folic acid deficiency in the
    current diet. High values are sometimes associated with inability to
    convert folic acid into other forms of folate, such as because of
    polymorphisms in the DHFR enzyme. They may also be due to high
    supplementation of folic acid.

    Folinic acid (WB): This is a measure of the concentration of folinic
    acid in the whole blood. See comments on 5-formyl-THF above. It
    usually tracks with the plasma 5-formyl-THF concentration.

    Folic acid (RBC): This is a measure of the concentration of folic
    acid in the red blood cells. The red blood cells import folic acid
    when they are initially being formed, but during most of their
    approximately four-month life, they do not import, export, or use
    it. They simply serve as reservoirs for it, giving it up when they
    are broken down. Many PWCs have low values. This can normally be
    caused by a low folic acid status in the diet over the previous few
    months, since the population of RBCs at any time has ages ranging
    from zero to about four months. However, in CFS it can also be
    caused by damage to the cell membranes, which allows folic acid to
    leak out of the cells. Dr. Audhya reports that treatment with omega-
    3 fatty acids can raise this value over time.

    Rich