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Transcobalamin TCN2++

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by SDSue, Mar 7, 2015.

  1. SDSue

    SDSue Southeast

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    @stridor I also am a mutant. I'd love to know what you've found out about TCN2 (I am TCN2++ and TCN1++). Did you have abnormal blood work that led your doctor to Rx daily injections?

    Dr. Ben Lynch of Seeking Health addresses TCN1 and 2 in this podcast. (Somewhere else he said that a double mutation is big trouble, but of course I can't find that reference.) I tried liposomal Methyl B12 as per Lynch, but noted no difference.

    Any other TCN++ out there? I'd love to hear how others are addressing this. Thanks!
     
  2. halcyon

    halcyon Senior Member

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    What are the specific SNP rsids to look for? 23andMe has a bunch for the TCN2 gene and a few for TCN1.
     
  3. SDSue

    SDSue Southeast

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    TCN1 ( rs526934 ) G is risk
    TCN2 C766G ( rs1801198 ) G is risk

    @halcyon
     
  4. Thinktank

    Thinktank Senior Member

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    My results

    TCN1 ( rs526934 ) = GG
    TCN2 C766G ( rs1801198 ) = CG
     
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  5. halcyon

    halcyon Senior Member

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    TCN1 ( rs526934) = AG
    TCN2 C766G ( rs1801198 ) = GG
     
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  6. stridor

    stridor Senior Member

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    @SDSue
    My B12 levels were always on the upper end of normal.
    I choose to view this as the B12 could not get into the cells where it was needed. In 2011, blood work indicated an above normal homocysteine. The Dr started to tell me that I needed to take B12 and folic acid but fell silent when he saw that I had been on these supplements for years.

    This was the opportunity to understand that something was wrong with methylation and that likely folic acid was the wrong approach...as was cyanocobalamin. Instead, the Dr's answer was to change the topic. Had he known more, I might have been saved from this path.

    I have not given TCN2 the attention it deserves...I just treat it. There is something going on and more research is needed. TCN2 is not particularly uncommon and the studies in terms of moving B12 into the cells is not all that impressive. Against this are the "Frailty Gene" studies where people with this are more likely to become frail.

    So, if you went to a nursing home and lined up all people, this gene would be over-represented in those who are considered to be frail.

    So, something is going on. Whether the affects are more pronounced with certain other SNPs or perhaps disturbances in the methylation system impact gene expression??? So a combination of genetics and epigenetics? It is over my head. I have stretched my college diploma to the max over the years trying to get well.

    The pendulum has swung back. If you read some of my earlier writing, at one time I thought that I had answers. What I have is a few "bricks of knowledge" largely derived from my n=1 experiences. I don't have enough bricks to really build anything. I can,and do, share them with others but I don't know how relevant they are.

    I do know that sublingual methylfolate and injections of mB12 have made my life livable again. And I suspect, but can not prove, that this would not have been possible until I took mercury out of the equation.
     
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  7. SDSue

    SDSue Southeast

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    Thanks, @stridor. You've confirmed what I am learning - there isn't much research in the way of TCN2.

    Your theory sounds similar to my conclusion, which is that the B12 is not getting into the cells if it's high in the blood yet I have all the classic symptoms of pernicious anemia, including peripheral neuropathies. The piece of the puzzle I couldn't find is whether or not transcobalamin is necessary to transport B12 into blood cells. If it is, then our theory is debunked.

    The bottom line, then, is whether or not super doses of the correct form of B12 can help.

    If I may ask, were you not successful with sublingual methyl B12 and that's why you do injections? Also, how much B12 and methylfolate are you using?

    Thanks so much. Maybe we can add another brick to your wall!
     
  8. PeterPositive

    PeterPositive Senior Member

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    I too have the TCN2++ and other B12 related issues... (see signature)
    Similarly I was not able to find compelling info about it. These days I am trying not to get too paranoid with the SNPs as there's a ton of them and it's close to impossible to understand how they all work and interact and how much weight do they really have in my health problems.

    In general B12 is helpful, I haven't found the sweet spot yet in terms of dosage. Recently I switched brand for convenience (Source Naturals) but I soon found out that it wasn't working too well as before (Enzymatic T.)
    Still experimenting.

    Also I've just started small doses of Lithium (1-2mg) to see if it helps.
     
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  9. Gondwanaland

    Gondwanaland Senior Member

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    Will you please report back on this?
     
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  10. SDSue

    SDSue Southeast

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    @PeterPositive It sounds like there might be many of us. I agree with not getting paranoid about SNPs, but then again, what about the ones that end up mattering lol? ;)

    This is a reasonable paper on TCN2 deficiency in adults. It explains the whole thing quite well, including the hypothesis that lack of transport into cells can result in high serum B12 levels. (bolding mine)
    Regardless, the treatment is pretty clear: More B12. I'd sure life to try IM, but without MMA or Hcy abnormalities, that's a tough sell.
     
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  11. PeterPositive

    PeterPositive Senior Member

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    Sure, it's only been a few days, so I don't have much to report. :)
    I will post an update in the near future.
     
  12. PeterPositive

    PeterPositive Senior Member

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    Makes sense. My B12 was at ~350, which is considered "fine" although I had lots of deficiency symptoms and Hcy level was through the roof.

    A few months after taking relatively low doses of methyl-B12 (250-500mcg) my serum level was already at 600+, although symptoms were still present.

    Well, you don't have much to loose. If more Methyl-B12 makes you fell better you are onto something otherwise you probably don't need it. Side effects are unlikely if you go slow.

    ETA: Ah sorry... You meant IM B12... make sense, although symptoms may trump labs, imo.

    cheers
     
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  13. stridor

    stridor Senior Member

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    @SDSue
    The theory is that transcobalamin is not absolutely necessary to move B12 into cells - give sufficient concentration it will diffuse across the cell wall. I thought of this as a "perfect storm". C677T provides only 30% of the methyl groups. These are attached less efficiently to B12 because of MTRR++....the decreased B12 that is present because of TCN2.

    To top it off mercury interferes with methionine synthase which is supposed to convert the homocysteine to methionine.

    My response to B12 was so strong that it was obvious that I had a deficiency state. The Dr ordered me mB12 injections and on my own I added sublingual. I used 15 mg tabs.
    For 18 month I bathed my cells with this with about 9000 mcg absorbed a day. I was taking in about 75 years worth of B12 daily in an attempt to accomplish this....about a third of what Freddd takes.

    Eventually, the citric acid in the sublinguals was chewing up my tooth enamel and so I backed off and just went with the 2 needles. I have tried twice to decrease but felt worse. I will try again ever few months to make sure that what I am going makes sense.

    I do not absorb mfolate well and I have to open capsules and pour it into my buccal pouches. I let my instincts guide me for the most part but an increase in brain fog will certainly trigger a dose. I don't measure and I don't count capsules but suspect that I am in the 2000-3000 mcg range on most days.
     
  14. SDSue

    SDSue Southeast

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    Perfect storm, indeed!
    May I ask what your "strong" response entailed? When I take methylation supps (B-12, methylfolate) I get extreme anxiety and agitation. I assumed this was a "bad" response, but maybe any response is "good'? It's confusing.

    Thanks so much!
     
  15. PeterPositive

    PeterPositive Senior Member

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    Even at low doses? Such as 50mcg?

    cheers
     
  16. stridor

    stridor Senior Member

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    @SDSue
    Some people are very sensitive - those with COMT for example. (I have one COMT++ but it is perhaps inactive or not one of the bigger players.

    When I started B12 it was about 3 weeks after being sent home from work "incapable to perform duties". I had extreme OI and brain-fog that made it difficult to function at any level. I was a complete mess. I had just had the ultrasound done at had CCSVI detected which is blood flowing the wrong way in my neck veins. I was on line complaining and a chap said, "you have CFS, Bipolar, mercury toxicity and "bowel cancer"? You are welcome at any of my family reunions - you have methylation problems".

    That started me down this road and I would eventually recover enough to understand this site. I came here earlier but couldn't read/comprehend well enough to benefit. I was also able to return to work and the same manager that sent me home, put me in charge of my work area.

    So, a night and day turn around. In my opinion, any response to B12 is a sign that it is needed. Start with tiny, tiny doses and work up incrementally. Take lots of magnesium.
     
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  17. garyfritz

    garyfritz Senior Member

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  18. SDSue

    SDSue Southeast

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    Yes. At least I think so - It's hard to detect patterns because of the ebb and flow of ME/CFS and also because I can't always remember what I took the day before lol.

    I, too, lost my job because of extreme OI (wasn't diagnosed until 2 years later - but laying on the floor unable to put a sentence together at work was a pretty good clue!) and horrific brain fog, among other things. "Complete mess" is a good way of putting it.

    That's amazing and wonderful. If only doctors knew this stuff! It's horrible to think how many people suffer needlessly with no clue.

    Working on it! Thanks so much for the tips.
    Great information, Gary! The Transdermals are officially on my wish list. It's certainly worth a try, given my dismal TCN status! Thanks so much.
     
  19. SDSue

    SDSue Southeast

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    @Gary, I forgot to ask: Which formulation(s) of Aussie transdermals are you using? Did you find it easiest to use the combos or dose each variation of B12 individually? Thanks!
     
  20. PeterPositive

    PeterPositive Senior Member

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    Try keeping a diary of your symptoms so that you can track your progresses or side effects.
    It would be a pity to ditch B12 and folate without absolute certainty that they don't work or are bad for you. Typically they can help significantly, for some people even dramatically over the course of some time.
     
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