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Low glutathione: amino acids or methylation?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by lolasana, Feb 12, 2012.

  1. lolasana

    lolasana

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    So it seems established that most of us have low glutathione levels (right?). How do we know whether these low levels are due to a partial methylation block or due to a deficiency of the amino acids necessary to make glutathione (cysteine, glycine, and glutamine)?

    My NutrEval results showed pretty low levels of glycine and glutamine and moderate levels of cysteine. My MMA and FIGlu levels were not out-of-range high. So is it possible that my low glutathione is due to a lack of amino acids rather than a methylation block? Do I need the methylation diagnostic test in order to know for sure?

    I don't understand why I have these amino acid deficiencies. My normal breakfast for the last year has been a smoothie with protein powder that contains at least a gram of all of these amino acids. It seems like I must not be absorbing the protein. Should I ask my doctor about the prescription pancreatic enzymes that are available? Has anyone had any luck with these (eg. Zenpep)?

    Taking the active B12s is definitely doing something for me; my mood is better and I am getting low potassium symptoms when I'm not careful (mostly muscle twitching and dizziness). But, I'm wondering if I need to address protein absorption too.

    Thanks!
     
  2. Freddd

    Freddd Senior Member

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    Hi Lolasana,

    Do you know how big a gram is? There are 28 of them per ounce.That could be an awful slim dose of protein. In any case make sure you get plenty of potassium. Be aware that things can get going well enough to outrun the Metafolin that you are taking in some people, the donut hole effect I posted about yesterday. I'll be posting a list tomorrow.
     
  3. lolasana

    lolasana

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    Hi Freddd,

    I mean a gram (or sometimes two or three grams) of the specific amino acids, not the protein in general. Though I probably do eat about 75-80 grams of protein a day.

    As I understand it, glutathione gets low and the B12 gets hijacked and lack of B12 breaks the methylation cycle. Without the methylation cycle going, sulfur is not properly regulated. Sulfur is required for glutathione production, so glutathione production is reduced. So it's a vicious circle.

    Here is where I get fuzzy: will re-starting the methylation cycle automatically restore glutathione production? As I understand it, glutathione production also requires cysteine, glutamate (or is it gluatmine?) and glycine. So if we are low in any of those amino acids, won't our bodies still not be able to make adequate glutathione even if we are methylating again?

    Maybe this is a separate issue. I don't know if it is common for people with methylation issues to be low in these particular amino acids. I'm just concerned because my glutamine and glycine levels were pretty low. I feel like I'm doing well with the B's but I'm worried that I'll be missing a piece of the puzzle if I don't address amino acid deficiencies. Has anyone else experienced this?

    Thanks!
     
  4. richvank

    richvank Senior Member

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    Hi, lolasana.

    Yes, if the amino acids are too low, the cells will not be able to make glutathione. Normally, the rate-limiting amino acid for making glutathione is cysteine, but if one of others gets too low, it will become rate-limiting.

    Amino acids are often found to be low in PWMEs. This can be caused by a low-protein diet, by poor digestion of proteins and absorption of amino acids by the gut, or by excessive burning of amino acids for fuel, because the burning of carbs and fats is limited in ME/CFS by a partial block early in the Krebs cycle at aconitase. Also, I think because of the last-mentioned issue, many PWMEs go low in B6 (or its active form P5P) because of heavy use by the transamination reactions. These are needed to convert one amino acid into another to feed them into the Krebs cycle, so when it goes low, there will be high and low levels of various amino acids, and it becomes difficult to feed them into the Krebs cycle for fuel. This then makes the person more fatigued.

    There are free form amino acids supplements, and supplementing B-complex vitamins can also help, if they are low.

    Best regards,

    Rich
     
    soulfeast likes this.
  5. topaz

    topaz Senior Member

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    Thank you for your response Rich.

    Would you advise supplementing with amino acids (specific ones or multi amino acids)? It appears that supplementing with glutathione precursors could be beneficial whereas taking glutathione is more of a band-aid measure (giving benefit to those taking it but no benefits continue once it is stopped).

    Thanks
     
  6. richvank

    richvank Senior Member

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    Hi, Topaz.

    If the essential amino acids in general are on the low side, then I would suggest first checking the stomach acid using the baking soda burp test that has been described several times on the forum. If it is low, there are things that can be done to raise it, such as taking betaine-HCl or Allergy Research Group dilute hydrochloric acid. That can help protein digestion. If the pancreas is not putting out digestive enzymes well, proteolytic enzymes can also be taken. If amino acids are to be supplemented, I would favor taking a combination supplement that includes all the essential amino acids, and then make sure the B-complex vitamins are high enough to carry out the transamination reactions needed to make the other amino acids in the body.

    To raise glutathione in ME/CFS, I've found it best to treat to lift the partial methylation cycle block. We found that glutathione comes up automatically if this is done, just as was found in autism by S. Jill James and coworkers. Boosting glutathione directly is just a temporary measure, as you mentioned, if there is still a partial methylation cycle block.

    Best regards,

    Rich
     
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  7. aquariusgirl

    aquariusgirl Senior Member

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    Rich
    You are such a gift!!
    I've been fooling around with B6 supplementation. I started because Susan Costen Owens over on the Trying Low Oxolates yahoo list said I needed it after reviewing my OAT from Great Plains.
    I'm taking quite a high dosage (which can cause neuropathy in some ppl & is not without other risks.....see wiki on this)..but it really seems to help.
    Today I got an amino acid IV (FreAmine 10%) & I added 2ccs of B6 & I must say my brain feels pretty good. I guess Peterson was right when he said aminos = brain food.
    So your comment above is very helpful for me.
    I got AA IVs in the past.. but I never had the B6 @ the same time.. and as I recall they weren't all that helpful.
    The FreAmine mix from BBraun is not ideal.. It contains lots of arginine for one thing.
    I was thinking of looking into a compounded, made to order mix, from a pharmacy like Apothecure in Texas, or Pure Compounding in Naperville, IL.
    Do you have any thoughts on what it should or should not contain?
    Below is a link to the BBraun formulation.
    Thanks
    AQ

    http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?id=24237&type=display
     
    soulfeast likes this.
  8. lolasana

    lolasana

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    Hi Rich,

    Thank you for your reply. My protein issues are definitely not due to low-protein diet! I get quite a bit of dietary protein. I will try the baking soda test that you mentioned for stomach acid.

    Test results have indicated that my Krebs cycle looks a bit slow. Could you say more about the Krebs cycle partial block? Is there a protocol for that like there is for the methylation cycle partial block?

    Thanks,
    Lolasana
     
  9. Freddd

    Freddd Senior Member

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    HI Lolasana,

    Adb12 and l-carnitine fumarate will get the krebs cycle ramped up for many people. That is of course against the backround of mb12, Metfolin and basics. That part of things isn't methylation, which is only a part of the whole.
     
  10. rydra_wong

    rydra_wong Guest

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    You should write down what you eat for 3 days and look up the protein amounts to find out what you really get. If you really get 80g of protein/day then you probably do not make enough HCL (stomach acid), which is what you need to digest protein (pancreatic enzymes are more for fats and starches). Search on line for the HCL test. I read about it in a book by Dr. Julian Whittaker but it is described online by others. After a meal of a certain size you try 1 HCL tablet. If it does not make your stomach warm, hot or irritated, then the next time you eat a meal of that size you cna try 2 (etc up to 7). If it DOES make your stomach feel warm, hot, or irritated then you back off tablet for a meal that size.

    I never was able to get a list of all the nutrients required to make HCL, but I know it requires zinc and P5P. I also know that hyperthyroid is one of the few conditions known to cause hypochlorhydria. (You can read more about hyperhyoid at www.ithyroid.com and please do not trust lab ranges as they encompass many serious health conditions and call them 'normal'. See www.lef.org for healthful ranges for FREE T3).

    P.S. I eat more like 40-60g potein and I do not have low protein levels. This is despite that I have a degree of hypochlorhydria. I take 50mg P5P every day. It does not lower my homocysteine as some here fear. I have measured homocysteine at 50mg P5P and 200 mg P5P and it has no effect on my homocysteine.

    P.P.S. If you have trouble digesting fats and starches as well as protein, start with HCL because it may take care of both. It is the HCL hitting the wall of the small intestine which catalyzes the pancrease to release its enzymes. (So you may not need any enzymes if you fix the HCL).
     
  11. richvank

    richvank Senior Member

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    Hi, lolasana.

    In my hypothesis, the partial block in the Krebs cycle is caused by glutathione depletion and the concomitant oxidative stress, including the rise in peroxynitrite. The methylation protocol corrects the glutathione depletion and lifts the partial block in the Krebs cycle, also. It can take some time to restore it to full operation, though.

    Best regards,

    Rich
     
  12. lolasana

    lolasana

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    Rydra: Thank you for your reply. I've tracked my diet several times. I naturally follow kind of a Zone like diet where about a third of my calories come from fat, protein, and carbs each. This generally means about 70 or 80 grams a day of protein. After I discovered my gluten intolerance (or possible celiac), I took HCL for about a year while my digestive tract healed. I slowly stopped taking it, but maybe I should have kept going. I still have a bottle somewhere. Maybe I should break it out and give it another try.

    Freddd & Rich:
    Thanks for yor help. It's good to know that fixing the methylation cycle should also fix the Krebs cycle. I'd hate to need yet another protocol, there's already so much to think about with the one! I'll look into the free form amino acids.
     
  13. lolasana

    lolasana

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    Sorry, I have one more question about his. I know NAC is not recommended for most people on the methylation protocol because cysteine levels are usually already high. But in my case, my cysteine levels are barely mid-range. Does this mean NAC might help me?

    Thanks!
     
  14. Valentijn

    Valentijn Activity Level: 3

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    I hadn't heard that cysteine is usually high ... maybe you mean homocysteine? When it comes to producing glutathione, cysteine is usually the most lacking of the three components. I tested high in the other two, and taking 1800mg/day of cysteine has helped a lot with sleeping and wired-but-tired sensations.

    It's possible that the B vitamins in the methylation protocol could fix a problem converting homocysteine into cysteine, and raise your levels that way. But even so, it shouldn't hurt to supplement cysteine, unless you have cysteine-based kidney stones.
     
  15. Freddd

    Freddd Senior Member

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    Hi Lolasana,

    NAC increases production of glutathione. Glutathione above a certain level appears to give some relief to neurological pain by numbing out the nerves more and appraently causing damage over a longer run. It appears to be capable of causing the very permanent neurological damage we are trying to heal here.
     
  16. Sallysblooms

    Sallysblooms P.O.T.S. now SO MUCH BETTER!

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    Glutathione is helpful for neuropathy. I am healing with it. Every study I have read says it is good. My doctors have me on NAC, Lipo GSH, Alpha Lipoic Acid... I have been healing from Autonomic Neuropathy. It is used as a protective agent for neuropathy.
     
  17. Valentijn

    Valentijn Activity Level: 3

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    What's the purported mechanism by which glutathione causes nerve damage?
     
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  18. Adster

    Adster Senior Member

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    I've found glutathione better than NAC if the b12 protocols aren't raising glutathione enough on their own. NAC affects mucus membranes by thinning out mucus which can be irritating. NAC is great for quickly getting glutathione levels up before or after chemical exposure though in the short term, it appears to work within hours.

    Freddd, I'm not suggesting you haven't seen anecdotal evidence of problems with NAC/Glutathione, but a few studies suggest it is actually neuroprotective. There may be others that suggest otherwise, I'm not trying to prove you wrong for the sake of it, it''s just that it seems quite beneficial for some people. http://www.ncbi.nlm.nih.gov/pubmed/15051148 http://www.ncbi.nlm.nih.gov/pubmed/19555676
     
  19. lolasana

    lolasana

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    Thanks for the replies everyone!

    I stand corrected, it seems that cysteine is usually low or low-normal in people with CFS. I guess I was thinking of homocysteine (or maybe cystine?).

    I just purchased some NOW NAC and I plan to give it a try in tandem with the b12 protocol. I did a bit of research on dosages and in clinical trials, it looked like dosages were anywhere from 1.5 grams to 3 grams/day. I'll ask my doctor for a personalized recommendation next time I see her. But, in the meantime, is there a dosage that you guys use while on the b12 protocol? (If you are using NAC; I realize it's not a required supp but I think it might help in my case since my cysteine is on the lower end.)
     
  20. Dreambirdie

    Dreambirdie work in progress

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    Hi lolasana--

    I have used both transdermal glutathione and N-A-C. I found the TD-glut to be a bit more effective at clearing my MCS type of toxic reactions, but because I have become allergic to the cream base and am breaking out in a rash from it, I have gone back to the N-A-C.

    I usually take 2 600 mg tablets (the Jarrow sustain) for mild toxicity, but have taken as much 3600 mg/day during times when I have a major heavy metal clearing going on. I find it can be a little harsh on my stomach, but it works well to help my liver clear toxins. IN fact sometimes it has been the only thing that has helped me.
     

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