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Resources on glutathione causing methyl block

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by PeterPositive, Mar 28, 2014.

  1. PeterPositive

    PeterPositive Senior Member

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    Hello,
    I've read here in several posts that oral glutathione is not recommended as it may cause a methyl-trap.

    My doc has put me on oral glutathione while taking methyl-folate and methyl-B12 and lo and behold my homocysteine levels have raised, while previously it was (slowly) going down.

    Might be coincidence or it might be the glutathione indeed. I'd like to talk to the doc about this issue with oral reduced glutathione but I'd like to provide some tangible evidence, not just mentioning that I "heard about it".

    Is there any research source that I can point him to?
    One of the thesis is that glutathione binds methyl-B12 inactivating it? Am I right? Can you point me to any study?

    Thanks in advance
     
  2. adreno

    adreno 3% neanderthal

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    I haven't seen any evidence supporting this idea. To my knowledge it is an idea advanced by Freddd. You probably need more B12 if taking it, but I don't believe it causes methyl trapping in most people. Maybe if you are like Freddd and have trouble getting enough B12 it could be an issue.

    That said, I believe it would be better for you to support your own production of glutathione, rather than supplementing it exogenously. From anecdotes it seems to be able to cause nasty side effects.
     
    Last edited: Mar 28, 2014
  3. PeterPositive

    PeterPositive Senior Member

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    Another option is that oral Metafolin is better than sublingual Quatrefolic.

    I have taken 1000-1200mcg of the former for 2 months an my Hcy was slowly improving, so I thought I would give a shot to sublingual Quatrefolic in hope it would work better and it didn't.

    I'd be happy to go back to Metafolin because I find that the same dose of Quaterfolic causes much more anxiety. Reason unknown.
     
  4. PeterPositive

    PeterPositive Senior Member

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    Thanks. Yes I think most of those posts where by Freddd.
    Maybe he has more info about it.
     
  5. WNM

    WNM

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    What is the exact level of your homocysteine?

    Low homocysteine levels may be caused by amino acid deficiency and/or excessive metabolism down the transsulfuration pathway to cystathionine/cysteine, possibly to support glutathione synthesis. In this case supplementing glutathione may spare homocysteine and raise levels.

    Note for a while the prevailing view has been that supplementing glutathione is ineffective due to it being broken down in the gut; however there is convincing evidence to suggest chronic supplementation does increase body glutathione levels (study). Also worth noting that supplementation with NAC can lower homocysteine levels; this is because the transsulfuration enzyme CBS can catalyse a reaction between cysteine and homocysteine to form H2S and cystathionine (study).

    Glutathione does bind with B12 to form glutathionylcobalamin. This form is thought to protect B12 and serve as precursor which when in the cell readily converts to the active coenzyme B12 forms (methyl and adenosylcobalamin) (studies). Hence this reaction between glutathione and B12 seems ok.

    Regarding folate, 5-mthf is the main natural form found in food and the dominant form in blood. Quatrefolic (glucosamine salt of 5-mthf) is the most recent form of 5-mthf on the market and is slightly more bioavailable than metafolin (calcium salt of 5-mthf) (see). Both forms are however really bioavailable and potent; 1000-1200ug is a large dose.
     
    Last edited: Mar 28, 2014
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  6. PeterPositive

    PeterPositive Senior Member

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    Hi WNM
    thanks for your reply.

    14 in the last bloodwork, was ~12 two months ago when I last tested and switched from metafolin to quatrefolic.
    I should add I am MHTFR C677T++

    My problem is not with low homocysteine. It's the opposite.

    Exactly, that's what I also gathered from a cursory research.

    Well, it is probably relative... I see people here use much higher doses.

    Of course there are other variables for methylation such as active forms of B2, B6 which I take in moderately high doses (~20mg each). The only two things that have changed are the addition of 1000mg oral reduced glutathione and Quatrefolic.

    Maybe my approach is too simplistic and I am ignoring other variables. I suffer from chronic functional GI issues and inflammation. I have yet to understand if this might be the cause of the consequence of hypomethylation or it's got nothing to do with it...
     
  7. WNM

    WNM

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    Sorry, I misinterpreted the situation, your homocysteine is a bit high. Sounds like you are taking plenty of all the most important B vitamins (B12, folate and B6). Could also try betaine/TMG. If you have digestive issues then betaine HCl may actually be quite appropriate. If you feel the glutathione has increased your homocysteine you could try leaving that out. Bear in mind plasma homocysteine increases during the day in response to food/protein intake, so ideally get fasting homocysteine measured (study).

    Some other considerations. Inflammation can upregulate methylation reactions, transsulfuration and GSH synthesis. Stimulated immune cells can release more homocysteine, which may occur due to oxidative stress and nutrient depletion (esp folate) (study). This is thought to underlie the association between inflammation and homocysteine in many conditions (e.g. sepsis, cancer and cardiovascular disease) (research). Vitamin and antioxidant-rich diet/supplements should be helpful here. A lot of people with gut issues go on a low carb/high protein diet which might also increase homocysteine. Vitamin D deficiency may also increase homocysteine levels. The VDR promotes CBS activity and homocysteine catabolism (study).
     
    Last edited: Mar 28, 2014
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  8. PeterPositive

    PeterPositive Senior Member

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    Thanks,
    Yes indeed, unfortunately I don't do well with both Betaine HCL and TMG, they both upset my intestine, especially the former. Go figure.

    Interesting. The study seems to suggest that the mechanism for increase Hcy is folate deficiency which I don't think it's my case since I already have high serum folate levels.

    Thanks, my diet is not very high in protein. I mainly use whole rice and quinoa as carbs which don't cause much fermentation.

    Vitamin D is definitely a problem for me. It may very well play a role in the picture...
     
  9. PeterPositive

    PeterPositive Senior Member

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    I also noticed that one study indicates resveratrol as a possible helper for high homocysteine.
    http://www.ncbi.nlm.nih.gov/pubmed/16197302

    Might be worth investigating. Resveratrol seem to have many other important functions, including anti inflammatory properties...
     
  10. Violeta

    Violeta Senior Member

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    Peter, have you tried B2 to lower homocysteine? For it to work, you might need to cut out folate and B12 for awhile.
    Per the I love B2 thread.)
     
  11. PeterPositive

    PeterPositive Senior Member

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    I take a moderately high amount of active B2 every day (25mg) but never tried without B12 and folate.
    Is there some sort of "conflict" between B2 and the other two? I thought B12, B9, B6, B2 all worked together.

    Gee, this is really confusing :) So many variables.
     
  12. Violeta

    Violeta Senior Member

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    It's not really a conflict, more just that a B2 deficiency can be caused by other B's. I'll see if I can find the message on this forum that explained it for me.
     
  13. Violeta

    Violeta Senior Member

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    Could it be that inadequate levels of glutathione reductase are available to reduce glutathione, causing a rise in homocysteine levels? I am truly asking, not saying it is so, as I don't know. I just happened to find that levels of glutathione reductase are dependent on B2.
     
  14. Little Bluestem

    Little Bluestem Senescent on the Illinois prairie, USA

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    I was instructed to stop taking B12 when I first started B2, but to resume it as soon as B12 deficiency symptoms appeared.
     
  15. PeterPositive

    PeterPositive Senior Member

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    Interesting. Never heard about this.
     
  16. caledonia

    caledonia

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    In his latest videos (linked in my signature) Ben Lynch mentions feedback inhibition caused by taking glutathione, also the importance of taking NAD with it, so that you make reduced glutathione and not oxidized glutathione.
     
  17. PeterPositive

    PeterPositive Senior Member

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    Thanks, I went back to the video.
    Dr. Lynch talks about Glutathione and NAD at around 27':00" for those interested. He also stresses the point about the importance of NAD which is interesting. He says that even with "OK levels" of glut. the lack of NAD can cause oxidized glutathione to remain "stuck" in the mitochondria.

    If I get this correctly the idea is that the oral (or IV) glutathione won't be able to do its job because the oxidized version can't get out of the cells...

    In any case my B complex does have NADH in it. The full dose is 13mg but I take ~ 1/3 of that. Maybe not enough?
     
  18. whodathunkit

    whodathunkit Senior Member

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    Does anybody know if NAD can soak up methyldonors in the way that regular niacin/niacinimide can?
     
  19. PeterPositive

    PeterPositive Senior Member

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    I don't think it's the case.
    I was reading this article a few days ago:
    http://www.sciencedaily.com/releases/2011/06/110602153040.htm

    So it seems to be useful in supporting methylation.
     
  20. PeterPositive

    PeterPositive Senior Member

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    To sum it up, from the various comments you have posted, there doesn't seem to be substantial evidence for glutathione supplementation to cause "methyl-trapping". Maybe besides some anecdote posted by Freddd and/or someone else following his protocol?

    It would be interesting to understand how much glutathione causes methyl-trap problems for those who have experienced it.

    Also I seem to remember from those anecdotes that old symptoms would flare up again with added glutathione. In my case I don't see any changes. My dosage is 1000mg/day reduced oral glutathione.

    @Freddd: care to comment?
     

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