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Is methylation without a doctor impractical?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by NilaJones, Jul 20, 2013.

  1. NilaJones

    NilaJones Senior Member

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    Omg, omg, Critterina, thank you so much!

    I actually have a degree in biochemistry from back in the day. But I have been so brainfogged for so long that I didn't even remember that the thing to do was to look at the cycle, and look at where my snps are, and figure out which direction reactions would be pushed. And I probably never would have thought of it, or not for years, if not for you. I used to frickin' tutor this stuff!

    I will print out your post, and print out the chart of the cycle, since flipping back and forth on the computer isn't working for me, and study them together.

    Thank you. Besides your enormous help here, you have given me back a piece of my life.
    Critterina likes this.
  2. Critterina

    Critterina Senior Member

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    Nila,
    That's so sweet! Yesterday was my first day on this site, and I could help someone already. It will be my turn soon to be helped, I'm sure.
    I took a year of biochem back in the day, too, 1980! Our textbook was Lehninger and my professor said that they were actually still debating some of the stuff in the conferences.
    I don't have CFS, have always been strong, mentally sharp, etc. But health issues the last two years have surfaced - very mysterious. And there is so much to learn!
    Valentijn and NilaJones like this.
  3. NilaJones

    NilaJones Senior Member

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    Heh, I will have to look at my old books and see if I had the same one :).

    And I know what you mean about being new and looking for ways to contribute! There is so much knowledge here, it's rare that I find a place where I can offer something useful. But you sure did :).

    I look forward to hearing what's going on with you. And who knows, maybe I will even come up with something helpful to say :).
    Critterina likes this.
  4. Valentijn

    Valentijn Activity Level: 3

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    I've never had a biochem class, but Lehninger's "Principles of Biochemistry" is the book we decided to buy to understand stuff a couple years ago. Very helpful and easy to read.
    Critterina likes this.
  5. NilaJones

    NilaJones Senior Member

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    Hi, Valentijn!

    I went and checked my bookshelf while printing. The one I kept is Voet & Voet. I loved that book! Very clear, very concise, very detailed. They have a fat version for upper div / grad classes, and a slim, edited version for lower div.
    Valentijn likes this.
  6. NilaJones

    NilaJones Senior Member

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    Ok, I spent some time with the chart and my snps and now I understand your post :).

    So, you are thinking that my 'tripping ballz' reaction to B12 is from too little neurotransmitter production, instead of (as I was thinking) too much? Maybe even from a buildup of ammonia and sulfur, as a result of pushing the reactions thataway? Or from decreasing the detox reactions in the urea cycle?

    And maybe the reason I feel better with methylfolate and no B12 is more neurotransmitters and less toxins?

    I took some folate last night, after not taking any since friday. It felt great, in a way that I could only describe to myself as 'clean'. It felt clean. It also felt like I had had my ears ringing and they had stopped -- not literally, but that feeling of absence of something that had been a continuous, low-level irritant.

    It also gave me mild insomnia, which it did not when I was taking it regularly. I don't know if that's bec I took it later in the day, or because I was not used to it. But I was surprised. I didn't know it had that type of effect.

    Ok, I think my brain just gave out for a while :).
    Critterina likes this.
  7. Critterina

    Critterina Senior Member

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    Yep, that's totally what I was thinking! And there's also the NOS that makes bad, bad, bad free radicals when there's not enough BH4 for additional oxidative inflammation.

    I've just started a low sulphur diet, eliminated my sulfur-containing supplements, and I know EXACTLY what you mean about feeling clean. Two days (and yesterday I tried low-thiol instead of low sulfur, so I had a piece of meat) of this diet and 5 days without the supplements, and I've lost 4.6 lbs and my belly is not sticking out like it was. It's like a miracle.

    Yep, I wouldn't be surprised if the folate kept you awake. Rawlins says to take it early in the day to avoid that. In fact, if you need to take 3 pills, I think he says to take the last one at noon. At least I think it was him who said it.
  8. Bluebell

    Bluebell Senior Member

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    Hi Nila,
    I would recommend my big list of methylation links that is in my signature line, below -->
    :)
  9. Bluebell

    Bluebell Senior Member

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    oh, you biochemists :nerd:

    to me it's just a spaghetti junction! :ill:
  10. NilaJones

    NilaJones Senior Member

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    And Critterina.

    Thank you!

    I am a bit overwhelmed today with new info and lack of sleep, so not posting much but I am reading and appreciating :).
  11. roxie60

    roxie60 Senior Member

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    So I am trying to support the SNPs I know need support but still no energy and now fighting depression more. I suspect BH4 cycle not working well. I did an ammonia test and expected it to be high but it was low (now I'm really confused). I am running out of time, I need to figure out what is clogging up my system. I do have many hetero MTR, MTRR and MTHFR polymorphisms. A video was suggested that happened to mention lythium being impacted by these mutations and further impacting B12 and BH4 conversions. Fatigue, memory, no energy and depression are currently my chief complaints (it amazes me how these symptoms come and go, two months ago no depression, they just seem to ebb and flow).

    First thanks to Caledonia if you did that 4 part methylation video, great job and keeping them under ten mins each great idea, even I could pay attention that long, although I still occasionally had to back up to re-listen.

    So I'm taking MB12 5000, Folate 1000, CoQ10, B complex, CereVive (has LDopa), Metanx, Tyrozine, L-theanine, flax oil, I cant recall the rest right now. So for others who have a number of hetero/homo MTR. MTHFR, MTRR and suspect BH4 issues what else are you taking? Do you also have low energy? Have you found anything that restores energy? I know these questions are so open ended but I'm feeling desperate to get better...... about 30 days left before hit wall and these Drs take so long with their evals. I am so frustrated and stressed. I really dont ever want to see another Dr and in a couple of months that wish will come true since I will have exhausted my cash funds to pay to see them, to pay for tests and to pay for supplements......:mad::confused:
  12. roxie60

    roxie60 Senior Member

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    Can someone tell me/show me the risk allele for ACAT 1-02? I have seen both A and G being shown as the risk allele, they both cant be.
  13. Bluebell

    Bluebell Senior Member

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    Dear Roxie60,

    I empathize with your situation (that you explained 2 posts above) and I hope things get better.

    I don't know of anything that would help, because I'm just floundering around in this area myself.

    ----
    What source says that G is the risk allele?

    What I have seen is:
    majority's alleles: GG (CC)
    minority's alleles and risk alleles: AA (TT)

    Yasko:
    "ACAT plays a role in cholesterol and other lipid balance in the body, helping to prevent the
    accumulation of excess cholesterol in certain parts of the cells in the body. ACAT is also involved in energy generation in the body. It is involved in helping to allow protein, fats and carbohydrates from food to be converted into an energy form that can be used by your body. In addition, lack of ACAT may also cause a depletion of B12, which is needed for the “long route” around the methylation cycle". // Yasko says this is a First Priority mutation - read more in her autism book chapter 6 step 2 part 1 and workbook page 76.

    "This gene encodes a mitochondrially localized enzyme that catalyzes the reversible formation of acetoacetyl-CoA from two molecules of acetyl-CoA. Defects in this gene are associated with 3-ketothiolase deficiency, an inborn error of isoleucine catabolism characterized by urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, tiglylglycine, and butanone."
    ncbi.nlm.nih.gov/gene summary

    varioius quotes from people here:
    "ACAT is a gene mutation related to fat metabolism and energy conversion. // Yasko says to treat the SNPs in a certain order. SHMT/ACAT, CBS, MTHFR, MTR/MTRR, BHMT, MAO A, SUOX, NOS, VDR. // the ACAT & SHMT. My doctor wants to know those two the most since these trump the MTHFR's and even the CBS! I guess the ACAT is horrible for gut issues, mitochondrial problems, urinary irritation, & kidney & bladder stones, the latter being due, I think, to oxalates // I am finding 4 hydroxylation of estrogen problems correlates with ACAT, CYP1B1, and downstream, SOD2 mutations. I am also finding other cholesterol mutations correlate with ACAT. I knew a homozygous ACAT mutation was relatively rare, but I had no idea that it could affect estrogen metabolism. // For ACAT, Yasko has an "everything but the kitchen sink" formula called ACAT/BHMT. the supplementation for ACAT is pretty complex (like 8 or 9 supps) // rs3741049 - ACAT1-02 (Risk Allele: A) Plays a major role in ketone body metabolism. Defects cause a 3-ketothiolase deficiency. Yasko believes it will cause an increase in gut bugs (particularly clostridia) as well as elevated fatty acid metabolites. //"

    "ACAT1-02 (acetyl coenzyme A acetyltransferase) plays a role lipid metabolism and energy generation. It can also deplete B12. As with CBS, Dr. Yasko views this as a first priority mutation. Going by Yasko's clinical experience, she says to address them first if you have elevated iron on a UEE, elevated iron on a UEE test, Short Chain Fatty Acid (SCFA) imbalances on a CSA test, suberic acid, beta hydroxyl methylglutaric acid, or other ketone and fatty acid metabolites imbalances on a MAP or OAT test; or if there are severe gut issues or muscle weakness (which can be related to aluminum retention)". She says people with ACAT or SHMT are more likely to experience gut dysbiosis. Because of disrupted flora, microbes may have an affinity for and retain toxic metals. Stabilizing the gut environment is very important."
    GeneticGenie

    "ACAT is involved in cholesterol and energy metabolism, helping to mediate the conversion of foodstuffs into biological energy. ACAT dysfunction may lead to B12 deficiency. Right now, I do not understand ACAT well and am not sure how important this is."
    Heartfixer site

    "Plays a major role in ketone body metabolism. Defects cause a 3-ketothiolase deficiency."
    SNPedia

    from a Yasko book (I don't know which) quoted by PhoenixRising member Star-Anise:
    "People with the SHMT and/or ACAT mutations sometimes have a greater tendency to experience gut dysbiosis and imbalanced flora. Until the flora are balanced, there’s a risk that the undesirable microbes will retain toxic metals. So, for those with ACAT or SHMT as well as other mutations (such as the MTHFR A1298C) that confer a greater likelihood of retaining aluminum, it is essential, prior to addressing these other mutations, to first stabilize the general gut environment via SHMT and/or ACAT support, by using supplements in the MPA received with your test results.​
    ACAT, (Acetyl-Coenzyme A acetyltransferase) impacts critical pathways and hence functional areas of human biochemistry in several ways, including:​
    • Helping to form cholesterol​
    • Assuring lipid balance and fluidity in the cell membranes, which in turns impacts neurological function​
    • Contributing to energy production via the Krebs cycle and its impact on the mitochondria, which signal cellular activity and supply cellular energy​
    • Mediating the accumulation of oxalates, which, in excess, can contribute to kidney stones and other health problems​
    ACAT contributes to cholesterol synthesis and membrane lipid balance. Bile acids are first synthesized from cholesterol and next conjugated to taurine. High taurine levels (often seen with ACAT) may reflect a lack of bile acids for conjugation. Since bile salts have been shown to increase ACAT activity, they may help ACAT issues. In addition, policosanol may help with membrane lipid balance and fluidity, which impacts neurological function. The next portion of the pathway that may be impacted by ACAT is the level of acetyl CoA, which feeds into the top of the TCA cycle (also called the Krebs cycle) at 12:00. Benfotiamine, riboflavin, and pantothenic acid support the reactions between pyruvate and the TCA cycle. In addition, a low dose of alpha lipoic acid (ALA) has been shown to replace acetyl CoA in certain reactions. Either a sprinkle of the ALA supplement or the topical ALA lotion can be used. More is not always better when it comes to support with ALA, although in some cases high dose ALA has been reported to have wonderful effects. ALA use should be based on both genetics and biochemical lab data.​
    A block at the acetyl CoA point of the Krebs/TCA cycle can also lead to both an accumulation of oxalates and increased levels of methylmalonic acid (MMA). To keep the cycle moving, the oxalates at 11:00 must combine with acetyl CoA coming in at 12:00. Low-dose vitamin K and lactoferrin help with that activity.​
    If both SHMT+ and ACAT + are present, begin with SHMT support first, and once that is in place, layer in ACAT support. Since high methionine levels appear to accompany ACAT mutations, SAMe, bile salts, glutathione (GSH,) and CoQ10 all can help to support the conversion of methionine. Curcumin and quercetin help shift the transulfuration pathway toward GSH. Since too much GSH can feed back and inhibit an enzyme that shunts to glutathione, I like to support the overall pathway rather than merely adding GSH."​

    PhoenixRising member Valentijn does not think the AA mutation is something to worry about:
    "There is 0 research about that SNP. The odds of it being relevant are pretty small (AA is common in some populations - up to 20%). You might as well roll a die or use your horoscope to decide if it's having any impact at all. "
    My response to that was:
    "I see two smallish samples where it's around 20% (both marked "Asian"), and two smallish ones where it's around 14% (one marked "Asian", and the other is Chinese people who are living in Denver, so basically also "Asian"). http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=3741049.
    Otherwise, the T/T / A/A is pretty unusual in other ethnicities/geographies."
    http://forums.phoenixrising.me/index.php?threads/cbs-acat-bile-salts.24417
    roxie60 likes this.
  14. Bluebell

    Bluebell Senior Member

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    I'm going to tag her here, so she has a greater liklihood of seeing your compliment! caledonia

    caledonia and roxie60 like this.
  15. roxie60

    roxie60 Senior Member

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    I memory serves I saw it in Thane's video which I watched today.
    about the 4:25 time stamp. You can see it in the genetic genie chart it shows 'G'. I thought the risk allele was 'A' so this was confusing me.

    BTW, thanks for the reply, I am reviewing it now and trying to comprehend.
  16. roxie60

    roxie60 Senior Member

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    When I saw the 'G' as the risk allele I thought maybe that would help explain the lack of energy (separate symp from fatigue although with some exertion fatigue kicks in). But if GG is the normal state then I cant use ACAT as a possible explanation since I am GG.
  17. roxie60

    roxie60 Senior Member

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    What I find interesting, confusing is I have had gut issues but SHMT normal (at least the one ident by Yasko). I do have major neurotransmitter issues also so I suspect BH4 cycle issue. I suspect some of the multiple MTR, MTRR and MTHFR hetero genes are dysfunctional to some extent. What came as major surprise last week was the plasma ammonia test I took came back low. I have never had ammonia tested before. I also had reduced/eliminated all meat so actually had little protein in the 10 days prior to the blood test so I have been wondering if that was enough time for the plasma ammonia level to drop.??? So much to figure out. My Dr wants me to consult with Sterling instead of reinventing the wheel on all this.
  18. Bluebell

    Bluebell Senior Member

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    That last column in the table is not showing the risky allele, it's showing the result that the specific person whose genes are being analyzed by GeneticGenie actually has.

    So the person in the screenshot you showed in your post has a "G" (GG) in his genetic data, and thus he gets a "-/-" in the third column of the ACAT line of the chart. His GG is considered not risky.

    If he had an "A" (AA) in the last column, then he would be given a "+/+" in the third column, and that would be considered risky.

    You can see the same thing in this image from GeneticGenie: http://geneticgenie.org/blog/

    Does this make sense to you?
  19. Valentijn

    Valentijn Activity Level: 3

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    I've put together a list of the 23andMe BHMT SNPs which have research showing the impact they have. It's at http://forums.phoenixrising.me/index.php?threads/interesting-bhmt-and-bhmt2-variations.24512/ , and might give a better idea of if and how badly things are malfunctioning.
    That's because it's a myth that upregulation of the Yasko CBS SNPs can cause us elevated ammonia, sulfur, etc. The real risk is with CBS running too slow. Some actually useful CBS SNPs and explanations are at forums.phoenixrising.me/index.php?threads/interesting-cbs-variations.24492
    MTRR ones are at http://forums.phoenixrising.me/index.php?threads/interesting-mtrr-variations.24551 and MTHFR are at http://forums.phoenixrising.me/index.php?threads/interesting-mthfr-variations.24543/
    roxie60 likes this.
  20. roxie60

    roxie60 Senior Member

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    yes, my brain just probably did not process correctly, thx. I thought the risk one was A.

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