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CBS Upregulation: The Only Reason for Low Homosysteine?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Kathevans, Aug 17, 2015.

  1. Kathevans

    Kathevans Senior Member

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    Right up front, I don’t have a scientific bent.

    So, when my doctor, whose methylation knowledge seems to be Yasko-centric, said I must correct my CBS snps before working on methylation or my pain would be worse, I was concerned, but not convinced.

    Blood work last December showed somewhat low homocysteine at <4.9 umol/L in a range looking for <9.0; and cystathione <dl, below range.

    At the time I was taking 2 Country Life Coenzyme B Complex tablet/day, as I had for a decade or more, and I was just beginning to understand that 400 mcg Methyl-Folate and 250mcg MeB12, given my snps, was probably putting me into methyltrap and causing the heaps of pain I was experiencing. It took me about six months of experimentation with the Bs, wading through pain, exhaustion, mania, depression and a visit to the emergency room to finally get off it. It felt like a true addiction I had to get rid of.

    I'm beginning to settle in to Nature Made’s B-complex—very low Bs/no methyl donors—and a bit of basic B6 @ 25 mg/day. I felt stable enough and clear enough about the issues last week to start a bit of MeB12--only at 250 mcg, which we know via Freddd means roughly 80mcg of absorption. Pain is less, I’m getting better at noticing the signs of methyltrap, even if I’m not yet addressing them. Which is to say, I'm wondering whether I need more folate, given all my veggies and salads, or more MeB12. Sleep is still a mess. Little steps, I tell myself. Patience.

    Part of me assumed that the folate:meb12 ratio was, for me, causing over-methylation and that this was a possible cause of the low homocysteine. My doc says, no. I pointed out my CBS C699T is fine, or in any case GG. I do have CBS A360A +/- (AG), which I see can have some, though less effect. In 2003, a study showed that these polymorphisms did not show a significant difference in homocysteine level due to the different genotypes. But…

    Both my Nutreval and OAT Tests were performed prior to getting off the B-complex, so I feel dubious about their results, though in them I have normal plasma Taurine (7.28 in a range of 5.00-8.50) and Ammonia levels, though I understand that it’s actually Urine levels that are important. (Not to mention that my eyes sting…and this has gotten worse since going off the B-Complex) Methionine was LOW, Glutamine/ Glutamate NORMAL and Glutathione 943 (in a range >=669)

    The doctor also said I might benefit from BH4 supplementation, though it was hard or impossible to get…

    He says basically that if I have low homocysteine, the symptom ‘proves’ I have Upregulated CBS. And from what I’ve read, if this is the case, increasing methylation will ultimately worsen things rather than improve them. (And it’s true, everything does seem inflamed) Even B6/P-5-P is said to be an “Ammonia Provoker”, something I ought to limit. Today I took a bit more because it seems to really help with sleep, not to mention oxalates!

    Should I be experimenting with the low sulphur diet? (which will be quite limiting as I’m already on the low oxalate/low carb)

    What’s important here? As so often happens, the more I read, the more confused I get. And this dull headache I have is definitely not helping.

    Thanks for any suggestions…
     
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  2. nandixon

    nandixon Senior Member

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    Assuming there's not any pathological reason for the low homocysteine, then if you'd like to try to raise it and see if that makes any difference in the way you feel, then since you mentioned low methionine, increasing that is an obvious thing to try based on the relevant biochemistry, I think. Either with foods rich in it or supplementing with the amino acid itself. Whether it makes you feel better, worse or unchanged is another matter.
     
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  3. Gondwanaland

    Gondwanaland Senior Member

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    @Kathevans my husband is +/+CBS 360A, and right now he is more sensitive to sulfur than ever. Apparently in the moment he starts to stir methylation, sulfur gets unbearable. I have tried to give him B1 + Molybdenum, but it made him depressed and the GI symptoms became awful (IBS-D, excess gas, discomfort). I don't know what to do. Focusing on probiotics right now.
     
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  4. Kathevans

    Kathevans Senior Member

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    @nandixon Yes, my doc did mention methionine supps and that is one thing I'll look into. Thanks. @Gondwanaland So is your husband on a low sulphur diet? And if, so, how long before a shift might be noticeable? Less inflammation, I'm assuming... For me bowel habits are improved with B12, though it may be I can get the same result (diarrhea largely resolved) from Dibencozide. As to symptoms, there are so many, I haven't yet assigned each to a cause!

    Today, I'm trying to see if a bit more B6 helps me with sleep. Unfortunately, as I've seen you comment, that first day result can often be wonderful...and misleading, and impossible to reproduce.:(
     
  5. Gondwanaland

    Gondwanaland Senior Member

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    Yes, the 1st time he took B1 all pain was gone, but never again.
    He doesn't follow a strict diet, but the days following a low sulfur day are markedly less painful. Obviously his gut is strongly out of balance.
     
  6. Kathevans

    Kathevans Senior Member

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    @Gondwanaland I have to say my diet is fairly high sulphur. I may try the no-sulphur for a week just to see if it helps. I read that eating meat is not a problem because it has whatever is needed to metabolize the sulphur in it. Or something like that! Unfortunately, I also eat fermented sauerkraut every day for its gut contributions and I'm loathe to give that up.

    This rebalancing of the gut is the challenge. My doc says I don't have a candida problem, but things are definitely out of wack and I suspect other fungal strains--ie the one from corn, possibly, as I do eat a lot of it in the form of polenta/popcorn etc. I've dipped into the resistant starch thread and have been consciously adding some of that to my diet, but haven't purchased Bob's Red Mill Potato Starch yet. Some people have had very good results with this.

    As to inflammation, I've also glanced at your "Balancing Nutrients" link and read about copper. You've had some good results with this, as I recall, and I know I'm low. I've slowly been titrating zinc drops (up to about 18 mg/day) and it may be time to add a drop of copper...
     
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  7. Gondwanaland

    Gondwanaland Senior Member

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    It is a low thiol diet, not a no-sulfur
    Usually I can't stand the histamines. Time to give it another go...
    Possibly aspergillus?
    I get unbearable joint pain from PS. Die-off? Oxalates from the potatoes processing?
    It is a vital mineral for those taking B vitamins!
     
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  8. Kathevans

    Kathevans Senior Member

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    @Gondwanaland Thank you for this very detailed response!

    You know we share the oxalate issues, of course, and the copper I happened to be definitely low in on my NutrEval test last December. I certainly got sidetracked by the B-Complex issue, probably compounded by the extreme oxalate issue beginning last winter...but I'm hoping to be coming out of this miasma. And therefor, better able to look at other issues.

    Yes, I've wondered about both these things, but as I said, I haven't given it a try yet. I'll let you know when I do!:thumbsup:
     
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  9. Valentijn

    Valentijn Senior Member

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    Where do you see that? I've never seen any research supporting that it has any impact, either when +/+ or +/-.
     
  10. Gondwanaland

    Gondwanaland Senior Member

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    I have this same status and feel the best on high sulfur, high thiol foods.
     
  11. Kathevans

    Kathevans Senior Member

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    @Valentijn I’m glad you jumped in.

    In fact, it was one of your older snp posts –Interesting CBS Variations,
    http://forums.phoenixrising.me/index.php?threads/interesting-cbs-variations.24492/
    that originally caught my attention.

    Supporting much of what you had to say, was a piece posted by an MIT researcher—CBS Upregulation, Myth or Reality? http://web.mit.edu/london/www/cbs.html

    One of the last things I read was-- What does a CBS gene mutation mean?
    http://resqua.com/702188759/what-does-a-cbs-gene-mutation-mean
    a decidedly Yasko-centric view that came back to the opinions expressed by my doctor and brought me back to the idea that having upregulated cbs was not a good thing. (Why o' why does Yasko call these 1st Priority snps???)

    You do point out in your thread that : there are three different ways in which homocysteine is disposed of: via CBS, via BHMT, and via MTR/MTRR. So even if your CBS is a little slow, the others (which are the more useful ones as well) might be functioning well enough to handle any excesses.

    Not that I need these, given my already low homocysteine. Like @roxie60 (who piped in on that thread), I have the CBS C699T GG (-/-) and, like her, also seem to have problems with p-5-p—it makes me very tired, too.

    Of course, my BHMT/MTR/MTRR have problems a-plenty, so maybe this is where I ought to be focusing…and leave the CBS behind…

    Though as I said, my methionine is low, as is my cystathionine.

    Oh, I'm totally confused.

    @Gondwanaland Yes! I’ve been eating high sulphur for years and it’s only lately that I began to wonder. I just don’t want to be shooting myself in the foot any more than I already have!
     
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