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Methylation Panel: Low SAMe,

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by kyzcreig, Jan 7, 2016.

  1. kyzcreig

    kyzcreig Senior Member

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    Seems like there's a block going from Met -> SAM.

    [​IMG]


    I found this thread which had a lot of good info by @DREBS
    http://forums.phoenixrising.me/inde...thionine-yet-blocked-methylation-cycle.23785/

    Apparently ATP and magnesium are the cofactors for Met -> SAM. I take loads of magnesium glycinate, it helps all my symptoms and helps my sleep so I don't think that's the problem.

    I did Genova's Nutreval and my krebs wasn't in great shape, so that might corroborate a low ATP hypothesis.
    http://imgur.com/pQLGBw2
    http://imgur.com/uJmmBK6
    Genova has an awesome interpretation guide for that and I've been following its suggestions.
    https://www.gdx.net/core/interpretive-guides/Organix-IG.pdf

    Does anyone have any other ideas, as to what might be the problem here?
     
  2. PeterPositive

    PeterPositive Senior Member

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    Do you know your levels of THF (tetra-hydro-folate) and B12?
     
  3. kyzcreig

    kyzcreig Senior Member

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    I remember seeing I had high serum folate and high b12. I take both regularly.
     
  4. PeterPositive

    PeterPositive Senior Member

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    It would be helpful to have a breakdown of the folate levels. I myself had very high "folic acid" in my standard labs but the lab itself doesn't say exactly which type of folate they measure under such label.

    I then did a full methylation panel (such as the one recommended by RichVanK) and it showed I had pretty high synthetic folic acid, sufficient folinic acid, barely sufficient 5-MTHF and insufficient THF.

    This in turn suggested that my B12 wasn't sufficient and was barely spinning the methylation cycle. Pushing more methyl-B12 has significantly improved the situation and provided some relief in a number of departments (mood, pain, energy)

    If you have more details about your folate status and a breakdown of the various forms it could help. Also serum B12 alone won't say much, unfortunately, although your low homocysteine suggests that B12 is working fine.
     
  5. kyzcreig

    kyzcreig Senior Member

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    That makes sense. Would this test be adequate: http://www.hdri-usa.com/tests/methylation/

    Perhaps it would be better to wait before doing another methylation panel (albeit more thorough with HDRI). I'm planning to supplement with SAMe but maybe that would be counterproductive. I know Yasko recommends supplementation if you're low but I want to address the root problem too.

    Looking at GDX's interpration guide: https://www.gdx.net/core/interpretive-guides/Amino-Acids-Interp-Guide.pdf
    And they recommend
    Which of course I'm doing.

    Here's what the interpretation from DD said:


    Google pulled up these studies:
    http://ajcn.nutrition.org/content/76/5/1177S.full
    http://www.ncbi.nlm.nih.gov/pubmed/26722840\
    Which state ROS (reactive oxygen species) and NOS (nitric oxide) deactivate methionine adenosyltransferase while reduced-glutathione reactivates it.

    For years I've had test results saying I'm low in Glutathione, this seems like another. Since the methylation cycle is what raises your glutathione levels, I'm not sure what I should do. Taking SAMe will probably raise the methionine levels further. I wonder if it's practical to take a lot of Acetyl Glutathione. I emailed the guys that supply Allergy Research and they would sell a kilogram for 1500 euros.
     
  6. PeterPositive

    PeterPositive Senior Member

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    Yes, that's the one I did. Sorry I didn't have a link at hand.

    You're probably right. I tried supplementing SAMe but it didn't tolerate it very well and it didn't make any difference.

    Glutathione works for me and it helps with inflammation.
    I have tried both normal GSH by Jarrow (500mg) and the super expensive Acetyl-Glutahtione and could not find any difference between the two so I am sticking with regulate GSH, 2x 500mg.

    cheers
     
  7. kyzcreig

    kyzcreig Senior Member

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    interesting, so I don't find oral glutathione makes a huge difference. at least normal GSH. but topical glutathione from kirkman or lee silsby makes my sleep much better and generally relieves symptoms.

    the research around acetyl glutathione is compelling but when i tried it before i experienced the same as you. i might try it at much higher doses and see if that's noticeable.
     
  8. PeterPositive

    PeterPositive Senior Member

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    Good point. The dosage with Acetyl form is usually lower, the one I bought comes in 100mg capsules and they say to take up to three, so it's 300mg/day.

    The Jarrow GSH (and most other brands) comes in 500mg and I've taken up to 3 a day. Even getting to a 1000mg with the Acetyl forms is pretty hard, requiring 10 caps... I've never tried that. I've tried up to 500mg and could not feel any difference. Kept going for a week and then I finished the bottle :) ... but I didn't continue since it is super expensive.
     
  9. kyzcreig

    kyzcreig Senior Member

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    I agree, but if the alternative is doing 10-20 glutathione IVs, that seems cheap by comparison. I'm probably going to look into doing it wholesale somehow. I wonder if anyone would be interested in a group buy
     
    PeterPositive likes this.
  10. kyzcreig

    kyzcreig Senior Member

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    Update: I've been taking large doses of acetyl glutathione, I buy directly from a laboratory in Italy (the same one that supplies Allergy Research) and have seen much improvement. You can buy it in bulk here: http://irc.bio/product/acetyl-glutathione/

    I'm still not sure what to do about low SAMe. I tried the Niacin-Exercise-Sauna detox protocol and had a huge flare of symptoms. I'm guessing this was because Niacin is metabolized by SAMe and depleted my stores.

    What can you do to raise SAMe cost effectively? IV therapy?

    I've been reading a whole lot of the research on SAMe and the enzyme family the produces it (MAT: Methionine Adenosyl Synthetase). In adults there's two isozymes for MAT, one in the liver and one in the kidneys. The one in the liver is deactivated by Nitric Oxide (I am a pretty vascular guy so I must have a lot), and oxidative stress. So that might be suppressing it. Scientific literature is sparse. Glutathione is mildly effective at reactivating nitrosylated MAT. They also recommend supplementing with endogenous SAMe. But the bioavailability of SAMe is low and its half life is short so it's not a tenable solution.

    I also read a study that demonstrated Glucocorticoids throttle the transcription of hepatic MAT. Another study verified this in humans. So, you could increase the amount of MAT enzymes by using hydrocortisone cream. In my subjective experience it works. But that has its own drawbacks e.g. messing with glucose metabolism.

    Still, if I have highly elevated NO (iNOS), that's probably the root issue here. How do I lower it? Mercola on what raises NO:
    • Allergies (histamine)
    • Poor iron status
    • Hypoxia (oxygen deficiency)
    • Carbon monoxide exposure
    • Excess estrogen or 'estrogen dominance'
    • Others
    Taking an anti-histamine does help with my MCS. I remember Dr. Rea (of EHCD Dallas) would prescribe histamine antigens, which deactivate histamine, and that helped too. Oxygen therapy via an oxygen concentrator or hyperbaric chamber also helps, but it can raise oxidative stress. Silymarin can help by increasing Glutathione recycling but lowers ferritin.

    Of note, TGF-beta lowers NOS expression. I have elevated TGF-beta, so maybe that's the body compensating. Insulin raises NO too. I tend to be insulin sensitive, one naturopath told me he only sees this level of insulin sensitivity in olympic athletes.
     
  11. renski

    renski

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    There needs to be more information available about this MAT enzyme inhibition, but these are other possible causes:

    MAT enzyme inhibition - can be due to inflammation, infection, gut dysbiosis, LPS from streptococcus, etc. Low energy/ATP, low magnesium and low potassium will also slow this enzyme
     

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