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What are the symptoms of ACAT issues?

Discussion in 'Genetic Testing and SNPs' started by Crossroads, Aug 31, 2015.

  1. Crossroads

    Crossroads

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    Hi everyone

    Short version: what symptoms should one expect with an ACAT1-02 mutation (heterozygous or homozygous)?

    Long version:
    I'm new here and have been reading and learning with great enthusiam, having recent gotten my 23andme results. I immediately started down the MTHFR treatment road (being C677T homozygous) taking methylcobalamin and methylfolate, as per Ben Lynch, but had to rein it back as I started getting some very strong reactions (intense neck and shoulder pain, awake all night), which I later realised were due to my CBS A360A homozygous mutation. Researching further, I found (thanks @caledonia !) some advice here that I actually need to treat ACAT even before I start the CBS protocol - going backwards to go forwards, if you will. However, as I am only heterozygous with ACAT1-02, and don't have obvious gut issues (apart from the occasional belch), I'm not quite clear what to expect with ACAT. I haven't found a description of expected symptoms. As I also have BHMT-08 ++ and BHMT02 +/-, I am considering taking Amy Yasko's supplement, but like to know what to expect before proceeding.

    I'm also MAO A R297R ++, and heterozygous for a couple of others (CYP2D6, both NAT2's, both VDR's, SOD2 and MTRR A66G).

    Thanks to everyone involved for a great resource. I'm feeling very optimistic about healing.
    Brian
     
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  2. Valentijn

    Valentijn Senior Member

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    None. The ACAT1 SNP on the Yasko SNP has no known impact.

    CBS A360A has no known impact. It is not causing reactions.

    BHMT-08 ++ is the mildly beneficial version. There's no research indicating that BHMT-02 every has any impact. Accordingly there is no reason to "treat" them.

    MAOA and VDR variations are very common. No idea about the CYP, NAT2, or SOD2. MTRR A66G only has an impact if it's homozygous.

    Basically Yasko is wrong more often than she's right. And if you buy her products you can primarily expect to pay a lot of money for small doses of substandard ingredients.
     
  3. ppodhajski

    ppodhajski

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    EVERYTHING I SAY HERE IS MY OWN OPINION. But I am finally getting off of disability for OCD/Anxiety after 15 years and I no longer have any ME or FM symptoms.

    Those SNPs may very well be important. If we have enough of the vitamin cofactor for a gene we will not have issues, but if we are deficient we have health issues. Having SNPs in these genes make us more susceptible to deficiencies.

    Your MAOA SNP points to a slow form of the enzyme. With this being slow you will retain more serotonin, dopamine, norepinepherine and epinepherine which might lead to mood issues and neurological issues. MAOA uses FAD (A form of B2, Riboflavin) as a coenzme. When we are low in B2 the MAOA enzyme will work slowly. And people with MAOA SNPs will tend to need more B2.

    Effect of riboflavin on monoamine oxidase activity in cultured neuroblastoma cells
    http://link.springer.com/article/10.1007/BF00716270#page-1

    Since you have an MTHFR SNP, that uses FAD (B2) as well, so I see that as evidence that you might have a B2 deficiency.. In my opinion I see taking the B2 cofactor for MTHFR as a better option than taking methylfolate. Taking B2 will increase methylfolate by directly speeding up the MTHFR enzymes.

    You can see that in action here:
    http://www.ncbi.nlm.nih.gov/pubmed/17932361
    Measures of riboflavin status improved in response to riboflavin supplementation. Riboflavin supplement enhanced the response to low-dose folate in people carrying at least one T allele and having polyps.

    Once you take the riboflavin you body will be able to use the folate in your diet more efficiently.

    There is a form of B2 you can buy called Flavin Mononucliotide (FMN) that might be better since it skips any possibility that you have issues with riboflavin absorption or metabolism.

    There are other genes other than CBS that Yasko and others do not look at. One of them is CTH. So One cannot say if this SNP impacts you or not. That is the problem with looking at single genes.

    I have nothing good to say about Yasko, she totally ignores vitamin cofactors.

    There is a lot more to look in your genetics to find what diet and supplements you might need so stick around!
     
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  4. caledonia

    caledonia

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    I have two family members with hetero ACAT and they have both had kidney stones. One of them has had pretty severe gut issues that took several years to work out. She still has to be careful about what she eats. The other one seems to be fine with the gut. There are also gallstone issues in my family (SNPs unknown).

    Heartfixer says this - ACAT 102: Acetyl Co-Enzyme A Acetyltransferase 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.

    So it sounds like getting some bile salts and/or keeping well hydrated, and then getting some B12 would be the thing to do for this SNP (outside of gut issues).
     
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  5. Valentijn

    Valentijn Senior Member

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    Approximately 28.5% of humanity is heterozygous or homozygous for ACAT1-02. Are you suggesting they are all at risk of getting kidney stones and/or gut issues?

    Whatever ACAT1 does, ACAT1-02 has never been implicated in doing anything. So maybe it's better to focus on SNPs which are known to have an impact, rather than endlessly speculating about what each of them might be doing, simply because Yasko arbitrarily put them on a list.
     
  6. ppodhajski

    ppodhajski

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    Chapel Hill, NC
  7. ppodhajski

    ppodhajski

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    And while there is little research that Rs3741049 SNPs chafe the metabolic rate of the SNPs there is no evidence that it does not either. In most cases we can assume that there is a change since that is the reason for most SNPs in the first place.
     
  8. Crossroads

    Crossroads

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    Hi @Valentijn @ppodhajski and @caledonia

    I appreciate each of you taking the time to respond. I see every one has very different approaches! Yasko seems less popular than I expected here. :)

    Ok, the reason I wrote that was after having read @caledonia's SNP Interpretation Guide, where the section about painful trapezius muscles jumped out at me,
    as that was exactly what I experienced, as well as nervousness and anxiety. So, what would your explanation be for those symptoms after taking methylfolate?

    I take it that you are recommending no action for the ACAT1-02, CBS and BHMT genes? Do you recommend I try again with the MTHFR protocol, or do something else first?


    @ppodhajski
    Thanks for the B2 recommendation - I hadn't realised how important it was. I've just started taking 36.5mg Riboflavin 5-phosphate Sodium daily. I think this is the same as the FMN you recommend. Any dosage recommendations?

    I hadn't heard of CTH. Assuming you are referring to this SNP, http://www.snpedia.com/index.php/Rs1021737 23andMe tells me that I have the normal GG expression, which is good to know.


    @caledonia
    Will take a look at the bile salts. I saw them mentioned before but was concerned about raising taurine and sulfur levels, which I assumed wouldn't help the CBS issue (which Valentijn now tells me isn't really an issue).

    On the subject of the CBS, I realise the right thing to do would be to actually test for expression. I'm having a difficult time procuring those urine sulfate strips here in Europe. Does anyone have a suggestion?

    thanks again everyone for being so helpful. Any other suggestions will be gratefully received!
    Brian
     
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  9. ppodhajski

    ppodhajski

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    That form of B2 it is not the same. It is closely related but not the same.
    https://en.wikipedia.org/wiki/Flavin_mononucleotide#Food_additive

    Source Naturals makes a pure form of FMN (Sublingual coenzymated B2). Any dose will depend on your own needs, start low and go slowly.

    And yes, that is the CTH gene I was talking about.
     
  10. Valentijn

    Valentijn Senior Member

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    There are billions of SNPs with no research into them. It would be shockingly inaccurate and ignorant to assume that every one of them is doing something significant simply because we can't be sure that they aren't.

    Then there is the little problem that most SNPs which have been researched have shown a lack of significance. It doesn't make any sense to assume a completely opposite trend in SNPs which have not yet been researched.

    Your basic underlying assumptions regarding genetics are completely false. PLEASE take a basic course in genetics, if you are capable of it. It might take a month or two, but there is so much you can learn from it.
     
    Last edited: Sep 2, 2015
  11. Valentijn

    Valentijn Senior Member

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    No idea. @caledonia also has no idea, but parrots Yasko and Heartfixer even when their claims are completely unfounded. When there is no research supporting their claims about the impact of SNPs, vague claims are made about "expression" despite that there is also no evidence that those SNPs can somehow become expressed to behave in a problematic manner. They are engaging in pseudoscience.
    Yes, there's no need to "treat" SNPs which are not having any impact. I wouldn't recommend either for or against a methylation protocol. That's something for you and your doctor to decide. If uncertain, a homocysteine blood test is a very cheap and easy way to see if there is actually a problem.

    If there is a problem, supplementing a normal dose of folate or eating a decent amount of vegetables has been shown to be sufficient in a couple studies involving the common MTHFR variations.
     
  12. Crossroads

    Crossroads

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    I appreciate your honesty. Great recommendation for the homocysteine test - I'll get straight on to that.
     
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  13. caledonia

    caledonia

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    If the bile salts make CBS issues worse, then treat CBS first, so you can tolerate them.

    The only two places I know to get the sulfate strips are directly from CTL Scientific or through Amazon.com. Or I guess you could find a friend in the US to act as an intermediary and order them for you.

    By symptoms, it does sound like you're expressing. The value in the strips would be to monitor when you're done with CBS treatment, so you know it's ok to retest methyl supps.

    Note that Ben Lynch also has a short version of a CBS protocol on this page (he calls it "opening up the sulfite pathway"), along with several other suggestions for getting through the Methylfolate Side Effects roadblock.

    http://mthfr.net/preventing-methylfolate-side-effects/2014/11/26/
     
  14. Crossroads

    Crossroads

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  15. Critterina

    Critterina Senior Member

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    Please explain the difference. My research led me to conclude they were the same.
    This respected publication shows the R5P structure and describes them as the same in the first line of the abstract. It wasn't the only publication I looked at, but I found nowhere that gave any other structure for either molecule. Thanks!
     
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  16. ppodhajski

    ppodhajski

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    First, I use the term FMN because it fits with the biology.

    riboflavin-5′-phosphate is the same as flavin mononucleotide. But riboflavin-5′-phosphate Sodium is not that same as flavin mononucliotide.

    There is only one company I know of that sells flavin mononucliotide (E101) without the sodium salt.

    https://en.wikipedia.org/wiki/Flavin_mononucleotide#Food_additive
    Flavin mononucleotide is also used as an orange-red food colour additive, designated in Europe as E number E101a.[1]
    "E106, a very closely related food dye, is riboflavin-5′-phosphate sodium salt, which consists mainly of the monosodium salt of the 5′-monophosphate ester of riboflavin. It is rapidly turned to free riboflavin after ingestion. It is found in many foods for babies and young children as well as jams, milk products, and sweets and sugar products."

    sn.png

    thorne.png

    It MIGHT have the same effect, but it is not the same.
     
  17. Kathevans

    Kathevans Senior Member

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    @Crossroads Like many on this site, I've done a lot of reading and through trial and error have begun to find some things that appear to be helping me. I am not a scientist, or even that conversant in the sciences!

    When I began to read seriously here, I had terrible pain in my neck--at times excruciating would be the word that comes to mind. At a visit to a new rheumatologist last December, he told me the reason my neck hurt so much was because my trapezius muscles were in spasm. He gave me prescriptions for a muscle relaxer, a pain killer, told me I had arthritis and that was that. (Long ago I was diagnosed with fibromyalgia by someone who wrote a book about it, but at this point who knows.)

    I had had the genetic test by 23andme last summer, and with information gleaned here, it seemed to me that the reason for this muscle pain and much more, had to do with my MTRR snps, or, I believe, my B12 assimilation. According to Freddd and others, in order for Folate to be absorbed in the cells, there has to be B12 there to help it out, or to combine with it. I admit to not knowing or understanding the chemical interactions.

    In any case, what I needed to do was begin taking the B12 very slowly...alone, without the Folate. It caused a lot of sleeplessness, as I've seen it does for some sensitive people. But slowly, I have adjusted to low doses, have added Folate, have discovered by observation that for me, when I increase the B12 and folate, my pain decreases. I mean in a major way. And when I now try to lower these two Bs, perhaps to give me a rest from other symptoms, the pain returns more intensely.

    What I am suggesting is that methylation protocols as proposed by a number of doctors and many here at PR, are dependent on your particular genetic snps. You can see in my signature that I have many issues in the MTRR area. What I have done has begun to work for me. I have also worked on slowly adding what are cofactors for many of the genetic snps, simple minerals like zinc and magnesium that I was low in, and in the case of magnesium, in particular, very important for all sorts of chemical reactions in the body.

    Good luck with your approach. There are many here who have a wealth of knowledge in all sorts of areas. It's not always easy, I find, to discover the threads that will speak to you. But over time, you'll find them, as well as those who will be able to speak more directly to your issues.

    I believe there is reason for hope.
     
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  18. Valentijn

    Valentijn Senior Member

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    I've also found B12 to be helpful for my ME pain. But folate seems to make no difference to me. Adding additional things from methylation protocols has also not been helpful for me.

    While I am homozygous for MTRR A66G (enzyme function reduced to 30% of ideal), the effects I get from B12 do not seem particularly connected to it. I was already eating a good amount of meat (the natural source of B12) on a regular basis, typically twice per day. And the amount I've been injecting has been far more than would be needed to replenish any stores in the liver which might theoretically have been depleted at some paint.

    But injecting hydroxoB12 twice per week, or taking a couple sublingual tablets per day, keeps most of the pain away. Unless I over-use a muscle, and then I'm still screwed :p
     
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  19. Kathevans

    Kathevans Senior Member

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    @Valentijn I have never tried injections, myself, and am not sure a doctor would prescribe them. My blood serum levels of B12 are actually high and my MMA test, I believe is mid range, though I have no idea what that means. My gut has been problematic, though, and I did take Zantac, an acid blocker for about 8 years. I've read that that can reduce absorption. I, too, eat meat on a daily basis (and lots of eggs!) yet something still must not be right. I've also read that those with fm can also have much reduced B12 in their cerebrospinal-fluid.

    In any case, the pain has been significant and the B12 helps. I think it was my OAT test that suggested an actual problem with folate metabolism, again, which I think goes back to the B12.

    At bottom, my strongest presenting symptom many years ago was non muscle recovery, and like you, when I over use my muscles, I suffer for it. My tendons have born the brunt of it where the muscles don't provide support, and I have a big tendon bump on top of my right shoulder because of the daily use of my right arm.

    I think both the Oat and the NutrEval test that showed a high need for Carnitine...that's for weight builders, right?! And it may be that ultimately that, in addition to the B12 will be of some help for my muscle weakness. It is, after all, part of the Deadlock Quartet!

    Meanwhile, the B12, now raised only to about 500 mcg/day (along with about 200mcg of folate) is playing havoc with my already poor sleep, and my appointment with the sleep doc is not till late October.

    Oy.
     
  20. Crossroads

    Crossroads

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    Thank you @Kathevans for a very thoughtful and considerate reply.

    Regarding B12, I have actually been on methyl-cobalamin for about a month, and find no problems tolerating it. The issue for me began when I started taking methylfolate. I started with 400mcg Methylfolate and the problems started when I increased it to 800mcg after two days.

    Thanks also for the tip about MTRR - I just checked, and I'm actually homozygous for MTRR A664A and heterozygous for A66G , so maybe I should be paying more attention to those. I understood though, that they were second priority SNPs, so had decided not to look at them for the moment.
     
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