A New Decade of ME Research: The 11th Invest in ME International ME Conference 2016
Mark Berry presents the first in a series of articles on the 11th Invest in ME International ME Conference in London ...
Discuss the article on the Forums.

Bill Walsh Finally Explains Over-Methylation In A Way I Can Understand

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by caledonia, Jan 2, 2015.

  1. caledonia

    caledonia

    Messages:
    4,450
    Likes:
    3,632
    Cincinnati, OH, USA
    Folks, I haven't really heard of Bill Walsh using acetyl named supplements to balance acetylation in neurotransmitters. I've read his book, Nutrient Power and from what I remember he uses more core/basic supplements like various minerals or B vitamins (or in certain cases, not using folate).

    I do suggesting consulting with a Walsh practitioner if these are major issues for you, instead of guessing what supplements to take. They do very specific lab tests to determine what supps are right for each person.
     
    picante likes this.
  2. Kimsie

    Kimsie Senior Member

    Messages:
    397
    Likes:
    410
    I have been reading Dr. Walsh's book the last couple of days and I think he has some really good ideas. This is the first time I have felt that anyone said anything about over or undermethylation that made any sense. However, he is talking mainly about the state of methylation of the histones, which I had not heard of before, not methylation in general.

    I don't understand why AGAT and GAMT would cause too much SAMe and although I might watch the video, I wonder if anyone can tell me about where in the video he talks about this is so I can go right to it. The synthesis of SAMe is normally regulated (slowed) by inhibiting MTHFR and upregulating CBS and that sort of thing and I don't see how GAMT or AGAT would have any effect.
     
    picante likes this.
  3. Kimsie

    Kimsie Senior Member

    Messages:
    397
    Likes:
    410
    Never mind, I found the spot at about minute 38. I still question whether this could be the cause of overmethylation, though, since as far as I can see SAMe is regulated by factors completely unrelated to these enzymes and if the enzymes are not working well, the body will simply make less SAMe. I am still holding to my former idea that overmethylation is simply a lack of niacin or niacinamide in the body, which I can explain in my hypothesis by the need for the body to have a larger NAD pool. This fits in very well with Dr. Walsh's idea that niacinamide helps overcome overmethylation.

    However, I really like Dr. Walsh's ideas about the cause of undermethylation and I feel it is very, very relevant for those who are undermethylators, which includes both of my sons. My son with depression, D, had fatigue until he started taking large doses of folate. Then after about 6 weeks on the folate he began to gradually become depressed. If Dr. Walsh is correct, then my other ideas about how the folate made him depressed are wrong and I have to revise parts of my hypothesis to include Dr. Walsh's ideas, which I am in the process of doing and I will be posting on it in a new thread pretty soon but right now I am still studying his materials and book and thinking it all through.
     
    picante likes this.
  4. caledonia

    caledonia

    Messages:
    4,450
    Likes:
    3,632
    Cincinnati, OH, USA
    AGAT and GAMT are upregulations. So even if MTHFR is slowing things down, there will still be a speed up at SAMe.
     
  5. Kimsie

    Kimsie Senior Member

    Messages:
    397
    Likes:
    410
    You are misunderstanding what he was saying. He said that the AGAT and GAMT are downregulations that cause the body to use less SAMe (because GAMT uses SAMe and AGAT makes the substrate for GAMT) and therefore there is "extra SAMe looking around for something to methylate."

    This doesn't make any sense because when SAMe levels rise it attaches to MTHFR and stops it from working and there are a couple of other ways high levels of SAMe slows the synthesis of SAMe. In other words, there is a feedback regulation for SAMe that has at least 2 or 3 backup ways to slow SAMe production when it gets high. People who have GAMT deficiency, which is an actual illness, don't have elevated methionine or SAMe levels.

    It looks to me as if what is referred to as overmethylation is not a general overmethylation, but overmethylation of the histones, which leads to higher amounts of serotonin, dopamine and norepinephrine in the synapses of the neurons. This is not caused by too much SAMe, but by other factors. I am studying this to try to get a better idea of what these factors might involve.

    I think Dr. Walsh's ideas about the state of methylation of the histones is probably correct and his ideas about treatment are very helpful, but not all of his ideas about what is causing it are correct. This is true of my own ideas, too (they are not all correct), and I am having to revise my own ideas again now to include what I have learned from Dr. Walsh's ideas, and I have to revise them pretty often as I learn more and more.
     
    Dreambirdie, ppodhajski and picante like this.
  6. Kimsie

    Kimsie Senior Member

    Messages:
    397
    Likes:
    410
    I took a closer look at the article I linked to above, and there is something else that can increase SAMe levels. It's when a person has less GNMT activity. I'm going to check this out more because glycine is something that is heavily involved in my hypothesis about these illnesses.

    Edit: It looks like if a person has less function of this enzyme they have high methionine so has anyone here had their methionine levels tested who also feels they are in the overmethylation category? Another possibility is low glycine levels. Does anyone who is overmethylated have low glycine?
     
    Last edited: Jan 22, 2015
    picante likes this.
  7. caledonia

    caledonia

    Messages:
    4,450
    Likes:
    3,632
    Cincinnati, OH, USA
    I'll have to recheck that again to understand it thoroughly. There were also a couple of functional situations he listed (beyond those SNPs) that would cause a problem with SAMe. So you could have the functional issues or the SNPs or both causing overmethylation problems.
     
  8. ppodhajski

    ppodhajski

    Messages:
    243
    Likes:
    258
    Chapel Hill, NC
    SAM is used by several methyltransferases, like COMT and HNMT, to degrade catecholamines (serotonin, dopamine, epinphereine). It makes sense that if SAMe si too high or low you can have mood issues. Note the MT on the end of those genes stands for methyltransferase.

    https://en.wikipedia.org/wiki/DNA_methyltransferase

    There are a lot of ways one can be low in SAM. A low methionine diet is one, or any slow enzymes (SNPs) in the methionine cycle will do it as well.
     
  9. PeterPositive

    PeterPositive Senior Member

    Messages:
    1,426
    Likes:
    1,035
    Wouldn't a test for homocysteine level give an indication of methionine insufficiency?

    E.g. in my case I have low SAM-e but high Hcy, suggesting methionine is not the limiting factor.
     
    Valentijn likes this.
  10. ppodhajski

    ppodhajski

    Messages:
    243
    Likes:
    258
    Chapel Hill, NC
    HCY test would just measure where in the cycle you are stuck. If you are B2, B12, or Zinc deficient this would stop you from recycling methionine. Add a N6 deficiency and your HCY is higher, Eating more methionine would just make HCY higher.
     
    PeterPositive likes this.
  11. PeterPositive

    PeterPositive Senior Member

    Messages:
    1,426
    Likes:
    1,035
    What is N6?
     
  12. ppodhajski

    ppodhajski

    Messages:
    243
    Likes:
    258
    Chapel Hill, NC
    Sorry, that was supposed to be B6
     
    PeterPositive likes this.
  13. Johnmac

    Johnmac Senior Member

    Messages:
    715
    Likes:
    423
    Cambodia
    @whodathunkit:
    So did you work out how to make the gains continue? I too have had lots of big gains from the FP - which don’t last.
     
  14. ahmo

    ahmo Senior Member

    Messages:
    4,431
    Likes:
    6,772
    Northcoast NSW, Australia
    @Johnmac Awhile back, on a thread about supplements, alex speculated that there's some mechanism that keeps pulling us back to some new (unwell) equilibrium. A very rough paraphrase. I wouldn't say that my gains haven't lasted, but there is a distinct ceiling on my cognitive and physical energies, that I've been unable to transcend. I shifted my focus to feeding the mitochondria and avoiding peroxynitrite with antioxidants. And choline is a big ingredient in mitochondrial health.
     
  15. Dreambirdie

    Dreambirdie work in progress

    Messages:
    5,330
    Likes:
    4,059
    N. California
    Hello @ahmo 2 questions...

    What are you using specifically to "feed" the mitochondria? Do you mean like the Wahl's diet?

    And what does "avoiding peroxynitrite with antioxidants" mean? Can you spell that out for me, please.

    thnx
     
  16. ahmo

    ahmo Senior Member

    Messages:
    4,431
    Likes:
    6,772
    Northcoast NSW, Australia
    @Dreambirdie I'm linking to some excellent mito threads. I think the correct fatty acids are pretty central, eg. phos choline. I'm sure the Wahl diet is a good baseline.

    Peroxynitrite is from Martin Pall's work on the nitric oxice cycle, NO/ONOO. There are 2 links in my signature. Central to this is antioxidants, listed in the last 20" of his vid.

    I've added various antioxidants this year, beginning w/ astaxanthine and resveratrol; olive leaf extract or tea, green tea. Most recently I added bilberry, French Melon, which is supposed to help w/ SOD, and acai. I don't experience any difference from the Fr. melon compared to the others, my body seems to prefer acai. I also eat a lot of carrots, w/ antioxidant properties. My body seems to prefer food-based antioxidants.

    http://forums.phoenixrising.me/index.php?threads/reverse-mitochondrial-damage-101.28175/

    Mitochondria 101 Part 2
    http://forums.phoenixrising.me/index.php?threads/mitochondria-101-part-2.29249/#post-446295

    Poisoning the Mitochondria

    http://forums.phoenixrising.me/index.php?threads/poisoning-the-mitochondria.27790/

    http://phoenixrising.me/archives/19805

    Mitochondrial Dysfunction

    http://forums.phoenixrising.me/index.php?threads/mitochondrial-dysfunction.12947/

    http://forums.phoenixrising.me/index.php?threads/resveratrol-mitochondria.25884/

    This is from a press release for Sarah Myhill's book last year:
     
    Last edited: Sep 7, 2015
    cph13, Oci, rosie26 and 1 other person like this.
  17. Dreambirdie

    Dreambirdie work in progress

    Messages:
    5,330
    Likes:
    4,059
    N. California
    Thanks @ahmo That will keep me busy for a while!
     
    ahmo and rosie26 like this.
  18. South

    South Senior Member

    Messages:
    466
    Likes:
    457
    Southeastern United States
    Well I'm glad some people understand Walsh's explanations. I'll have to watch this thread or future threads about it until it can be simplified though, none of it makes any sense to me still.
     
  19. Johnmac

    Johnmac Senior Member

    Messages:
    715
    Likes:
    423
    Cambodia
    Sorry @ahmo - just saw this for some reason.

    I've managed to prevent the reversals of gains this time, by simply following the protocol (d'oh). The main thing has been to ramp up doses once gains start to melt away (as Freddd recommends). That's resulted in some great progress. (I was barely functional 3 months ago - now I can work full time.)

    I wonder if this could be relevant to the slide back into depression by @Kimsie's son (above). Freddd lists "reappearance of old symptoms" at the top of his list of paradoxical folate deficiency symptoms - i.e. the symptoms you get if you don't keep increasing doses.

    I don't know how well this approach works for others, but it does work for me.
     
    ahmo likes this.
  20. Kimsie

    Kimsie Senior Member

    Messages:
    397
    Likes:
    410
    Hi Johnmac,I have finally come to realize that the reason that folate causes depression in my son is because high dose folate can greatly increase the capacity to synthesize glycine through the SHMT enzyme. This would be complicated to explain completely here, but I will probably explain why I believe this happens in another post, but not quite yet. The upshot is that taking large doses of folate creates a black hole for B6 and zinc in my sons because it supplies glycine which feeds the metabolic pathway which is draining the B6 and zinc.

    The "reappearance of old symptoms" that you are talking about, in which a person continually needs to increase the dose, or in many cases simply means that when a person takes a supplement or supplements that are helping they often only work for a limited time and the person gets the symptoms back again - I believe that this is because what is actually happening is that the person's body is compensating for something abnormal that is going on by making changes in genetic expression and upping the dose of the supplements pushes enzymatic pathways so that these changes in genetic expression are overcome until the body has time to adjust the enzymes in those pathways back to where it is compensating for the something abnormal . The something abnormal isn't causing perceptible symptoms, it's the compensation that causes distressing symptoms. If the person is very low on whatever is supplemented, then this process can go on for quite a while with small increases in doses of the supplements, but if they are not low, it takes a large dose of the supplement to have an effect and eventually they reach a point where the dose is so high that it doesn't work any more - this has been our experience.

    If the something abnormal that the body is compensating for is a deficiency of one of the supplements that the person is taking, then gradually raising the levels of that supplement will eventually have a lasting effect when the person reaches the level of supplementation where that vitamin or other substance is no longer deficient.
     
    Beagle, South and Johnmac like this.

See more popular forum discussions.

Share This Page