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glutathione, autism, test and treatment

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by alexa, Mar 17, 2011.

  1. alexa

    alexa

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    i have been diagnosed with CFS/ME for about two years now and been finding many interesting things on this forum, although this is my fist post ( hi everyone!)

    I am reseaching if it is possible for me to have a baby and i am concerned with the link between CFS and autism. One of these links seem to be glutathione. My questions are:

    1.can i get tested to see my levels of glutathione?

    2. There seem to be some difference in how it should be administrated? what does a newbie start with?

    3. Can i start with only glutathione or do i have to do a whole protocoll? ( i have tried with b12 sublingualy and all i got was a very strange headache

    i desperatly want a baby but i don't want to do anthing stupid...
  2. richvank

    richvank Senior Member

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    Hi, Alexa.

    In my opinion, the best test for glutathione is the plasma reduced and oxidized glutathione combination offered by the Health Diagnostics and Research Institute as part of their methylation pathways panel. This panel will also indicate whether you have a partial methylation cycle block and draining of folate metabolites from your cells. The contact information for this panel is pasted below.

    After several years of trying to find ways of building glutathione in people with ME/CFS, I learned from autism research that the way to do it on a permanent basis is to treat to lift the partial methylation cycle block. If that is done, we have found with lab testing that glutathione rises up to normal automatically, just as was found in autism by Jill James et al.

    In order to lift this partial block, it is necessary to take high-dose B12 sublingually or by injection, together with chemically reduced folate, preferably L5-methyl tetrahydrofolate (sold as Metafolin or FolaPro) taken orally. Most PWMEs/PWCs also need some other supplements, especially if there are some deficiencies.

    Methylation treatment does produce some symptoms at first. I think it is due to the mobilization of stored toxins when the detox system begins functioning more normally.

    I've known of several women with ME/CFS who have delivered healthy babies, though there has been some information from doctors suggesting that there is a higher rate of miscarriages among women with ME/CFS. Some women have actually felt better themselves while pregnant, while others have felt pretty badly. I have been the only male member of the Yahoo CFIDSorFMSpregnant2 group for several years. I joined to learn whether it was true that women felt better during pregnancy, as a clue to understanding this disorder. The group is pretty inactive now, because most of the women who initially joined the group either had children or adopted them, and got very busy! I think it started about 8 or 9 years ago.

    My own opinion at this stage of our ability to treat ME/CFS is that it would be a good idea to do the methylation treatment before getting pregnant, but I understand about the biological clock, and this is an individual decision for each couple to make.

    Best regards,

    Rich

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


    Available from:

    Health Diagnostics and Research Institute
    540 Bordentown Avenue, Suite 2300
    South Amboy, NJ 08879
    USA
    Phone: (732) 721-1234
    Fax: (732) 525-3288

    Lab Director: Elizabeth Valentine, M.D.

    Dr. Tapan Audhya, Ph.D., is willing to help clinicians with interpretation of the panel by phone, or the following guidance can be used for interpretation:

    Interpretation of the Health Diagnostics and Research Institute
    Methylation Pathways Panel

    by
    Rich Van Konynenburg, Ph.D.


    Several people have asked for help in interpreting the results of
    their Health Diagnostics and Research Institute 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., at the Health Diagnostics and Research Institute.

    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. Audhya, 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 likely 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 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 many biochemical reactions depend on it for their methyl
    groups. A low value for SAM represents low methylation capacity, and
    in CFS, it appears to result from a partial block at the enzyme methionine
    synthase. Many of the abnormalities in CFS can be tied to 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. Many 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 with toxin buildup.

    10-Formyl-THF: This is a measure of the concentration of 10-formyl
    tetrahydrofolate in the blood plasma. It is usually on the low side 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 value on the low side. 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. In PWCs 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 normally 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 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.
  3. alexa

    alexa

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    thank you so much for the quick answer, you were just the person i was writing to!
    some additional questions, what is PWMEs/PWCs ?
    how long can one expect the adverse reactions to the protocoll to last?
    I will absolutly to to lift my block before i consider pregnancy, i am "only" 27 but i know that treatment for cfs takes time, might as well start now!
  4. lizw118

    lizw118 Senior Member

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    <<Some women have actually felt better themselves while pregnant, while others have felt pretty badly. I have been the only male member of the Yahoo CFIDSorFMSpregnant2 group for several years. I joined to learn whether it was true that women felt better during pregnancy, as a clue to understanding this disorder. The group is pretty inactive now, because most of the women who initially joined the group either had children or adopted them, and got very busy! I think it started about 8 or 9 years ago.>>

    Of all of the treatments I have tried for my CF and autoimmune stuff, estriol cream has been one of the most dramatic for me. Estriol is very high in the third trimester of pregnancy. I have no idea why it works for me, but it seems to have an effect on my nervous system dysfunction, so my POTS is better, and I don't have sinus headaches, etc. It also gives me more energy and seems to have an anti inflammatory effect, too. I have to take the cream in high doses, though, to get the effect. I wonder if it is the estriol that helps these women feel better while pregnant. I know there has been a study on using it for M.S. Rich do you have any thoughts on this?
  5. richvank

    richvank Senior Member

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    Hi, Alexa.

    PWME is an acronym for "person with myalgic encephalomyelitis," and PWC is "person with chronic fatigue syndrome."

    The best-documented information I have about the responses people have had to the simplified treatment approach protocol is in our 2009 poster paper for the IACFS/ME conference:

    "Various patients reported some early exacerbation of symptoms, which in most cases was followed by a greater improvement in symptoms. Three of the patients found it necessary to decrease their dosage frequency to every second or third day for several days, until they could tolerate the full daily dosage schedule.

    "Sixteen of 30 patients (53%) reported an initial worsening of symptoms, beginning in most of these cases within 3 or 4 days, but in some cases beginning at up to 2 weeks. Most of the symptoms were mild, and none of the patients discontinued usage of the supplements during the first 3 months. The most common side effects were gastrointestinal (pain, cramps, constipation, or diarrhea), reported by 6 out of 30 patients or 20%; increase in pain, reported by 4 out of 30 or 13%; and increase in fatigue, reported by 3 out of 30 or 10%. Other symptoms, reported by one patient each, were a decrease in appetite, poor sleep, weak legs, flu-like symptoms, and an increase in anxiety and depression.

    "For those who experienced improvement, the time to self-reported improvement on the protocol was an average of 5.6 weeks, with a range from immediate improvement (which was rare) to as long as 8 weeks before improvement was experienced."

    I hope this is helpful.

    Best regards,

    Rich
  6. richvank

    richvank Senior Member

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    Hi, lizw.

    Thanks for sharing your experience of benefit from estriol cream. Perhaps this does explain the improvement some women with ME/CFS report during pregnancy. There have been other hypotheses suggested, and it's difficult to say which of them might be valid. One is that the total blood volume increases during pregnancy, and that would help to counter the diabetes insipidus (not the same as diabetes mellitus) that many PWCs have. Another is that the placenta has good antioxidant capacity, and that might be helping to lower oxidative stress in the pregnant woman's body. Another is that perhaps the rate of metabolism (breakdown) of the estrogens is decreased in order to raise their levels, and this would eliminate the redox cycling that may be occurring in women who have polymorphisms in certain detox enzymes that can be involved in metabolizing estrogens: CYP1B1, COMT, the GST enzymes, and the SOD enzymes. I have suggested that the higher prevalence of ME/CFS in women is due to this redox cycling process during the metabolism of the estrogens. It doesn't seem that that explanation would fit your case, though! Thanks again for the information.

    Best regards,

    Rich
  7. lizw118

    lizw118 Senior Member

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    <<Another is that perhaps the rate of metabolism (breakdown) of the estrogens is decreased in order to raise their levels, and this would eliminate the redox cycling that may be occurring in women who have polymorphisms in certain detox enzymes that can be involved in metabolizing estrogens: CYP1B1, COMT, the GST enzymes, and the SOD enzymes. I have suggested that the higher prevalence of ME/CFS in women is due to this redox cycling process during the metabolism of the estrogens>>

    Hi Rich
    This is very interesting information. I am not sure I understand what the redox cycling process is, though. Is there an easy way to explain it (probably not!) Thanks as always for your informative posts. I often reread them
    liz
  8. richvank

    richvank Senior Member

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    Hi, liz.

    When there are polymorphisms in the enzymes CYP1B1, COMT, the GST enzymes and the SOD enzymes, estradiol is not metabolized by the usual pathways, and instead is diverted into forming what is called a quinone. Then the quinone oscillates back and forth between being a quinone and being a semiquinone. Each time it goes through one of these cycles, it forms a superoxide ion, which is an oxidizing free radical. If the SOD enzymes are not operating as they normally do because of polymorphisms, it will make the oxidative stress even worse.

    The redox cycling mechanism has been studied for several years, because it may have a role in causing certain cancers.

    I have proposed this mechanism as the explanation for the higher prevalence of ME/CFS in women than in men. As far as I know, there haven't been any other proposed explanations of this observaion in any detail. I presented a poster paper on this at the 2007 IACFS/ME conference. The idea is that women during their potentially reproductive years would have an additional bias toward oxidative stress if they have these polymorphisms. Oxidative stress depletes glutathione, and I have proposed that glutathione depletion is what brings on most cases of ME/CFS. I've found men who have these same polymorphisms, but it doesn't cause redox cycling in them, because they aren't producing estrogens at such a high rate.

    Best regards,

    Rich
  9. Shellbell

    Shellbell Senior Member

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    Hi Rich,

    This is all very interesting. I am glad that this topic has come up.

    Six years ago I had a total hysterectomy. Because of my age at the time (40), I was placed on bioidentical hormone replacement therapy. It was after this, coupled with my adverse reaction to cipro, that my health took a dive.

    I have been ill for 3 1/2 years now. After my cipro reaction, a hormone doc thought that my problems were hormone related (not cipro) and switched my prescription from biest (combo estriol/estradiol) to straight estradiol. He doubled the amount that I was taking as my tested levels were non-exisitent. I take this with progesterone and DHEA, all in oral form. My testosterone is given in topical cream form.

    (Btw, before getting sick, I tried taking all my hormone in cream form and had a rough time balancing them. They decided to keep in mostly oral since it seem to be more stable for me.)

    I have often wondered if my high dose of hormones is the reason why my body is having a hard time recovering. My hormone levels are all over the place, with estrogen and testosterone levels sometimes high normal to really high depending on the day. Progesterone and DHEA, however, are always low. I think this is because of the high doses of estrogen surpressing the progesterone and adrenal function.
    We recently but my testosterone levels down by a 1/3. We haven't retested yet.

    One of my docs suggested lowering my dosages and switching back to the biest because the estradiol levels are lower in that combo. My other docs have suggested to leave them alone until the liver is cleaned out enough to start processing the hormones again.

    My gut feeling is that if I were to switch estrogen replacement types back to biest, lower the dosage, and switch to the transdermal type, maybe I would have a chance of repairing my body.

    I know estrogen can have a great impact on the liver/gallbladder, which is an area I am really struggling with. I just wonder if it is having an impact on my ability to heal.

    Any thoughts about this would be appreciated. Just a note, in the past since being ill, when we have tried to lower my hormone dosages, I get incredibly ill and crash very hard. This is one reason why my current doc is reluctant in changing anything at this point, even though we did lower testosterone a bit. But, as I said above, will lowering the dosages help in my recovery, freeing up pathways to better detox?

    I am doing the b12 protocol and have been at this for about 5 weeks. Since starting this, there is evidence that my liver/gallbladder are taking a pounding at the moment. A recovered CFS friend of mine suggested I stop my hormone therapy all together. But this isn't an option as I don't have my ovaries anymore. After my hysterectomy, they starved me of hormones because of endometriosis and I became a horrible mess for about 6 months before they corrected my hormones with replacement therapy. Once they got my hormones back up to par, I felt great. It wasn't until the cipro incident that my hormones became a mess. And no matter what we do, we can't seem to correct them.

    Again any suggestions are greatly appreciated!!

    Thank you,
    Shelly
  10. Shellbell

    Shellbell Senior Member

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    Not sure if it matters, but I am taking the following everyday:

    Estradiol - 1.66mg
    Progesterone - 400mg
    DHEA - 20mg
    Testosterone - 1/2mg

    What I was on before getting ill was half the dose of estradiol and progesterone and 1mg of testosterone a day.

    Thanks again,
    Shelly
  11. lizw118

    lizw118 Senior Member

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    Hi Shellbell
    If you take your hormones sublingually, they will not be so hard on your liver. That might help a little. Are they in tablet form? I take estriol tabs sometimes and I dissolve them under my tongue. Same for dhea. I do believe that hormones play a part in CFS for women sometimes. At least your doc is not scared to give you estradiol. I actually have good luck with estriol and not with progesterone, but everyone is different. I hope you find the solution!
    liz
  12. lizw118

    lizw118 Senior Member

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    Hi Rich,
    COuld someone test for these polymorphisms? Do you think the methylation protocol can help this problem?
    Thanks for your excellent explanations, as usual
    liz
  13. richvank

    richvank Senior Member

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    Hi, liz.

    You're welcome.

    These polymorphisms are all characterized on the Genovations Detoxigenomic Profile, available from Genova Diagnostics. In the past I've received data from people who had that panel run. It may be that these polymorphisms are included in the large number of polymorphisms characterized by 23andme and their competitors in their haplotype-based analyses, but I don't know that for sure. Their price has come down lately.

    Best regards,

    Rich
  14. richvank

    richvank Senior Member

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    Hi, Shelly.

    I think it would be helpful for understanding your case to run the Genovations Detoxigenomic panel, for two reasons: It will look for polymorphisms in the enzymes associated with metabolism of the estrogens, and it will also characterize polymorphisms in CYP1A2, which is used for Phase 1 detox of Cipro. If you have polymorphisms in both, I think that would help to explain what has gone on in your case. Cipro, being a quinolone antibiotic, is known to chelate ions having +2 and +3 chemical oxidation states, especially magnesium, but several other essential minerals also. It is also known to deplete glutathione and produce oxidative stress. If you have the polymorphisms that cause redox cycling when metabolizing estrogens, and also have a polymorphism in CYP1A2 that slows down the detox of Cipro, I think the combination could cause a lot of oxidative stress when supplementing estrogens and also getting treated with Cipro.

    I would also suggest running the methylation pathways panel mentioned earlier on this thread. It will tell you about the status of your methylation cycle and also glutathione. It could be that these factors lowered your glutathione and brought on a partial block in your methylation cycle.

    Best regards,

    Rich

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