Severe ME Day of Understanding and Remembrance: Aug. 8, 2017
Determined to paper the Internet with articles about ME, Jody Smith brings some additional focus to Severe Myalgic Encephalomyelitis Day of Understanding and Remembrance on Aug. 8, 2017 ...
Discuss the article on the Forums.

What does high B12 mean?

Discussion in 'Diagnostic Guidelines and Laboratory Testing' started by seethatlake, Jul 17, 2017.

  1. seethatlake

    seethatlake

    Messages:
    13
    Likes:
    2
    Australia
    Hi guys. I've had high active vitamin b12 now for a few years and I have no idea what it means or why it's occurring. I have the MTHFR mutation (homozygous) and my practitioner wants me to take high doses of B12 but I'm concerned that I'm not breaking it down or utilising it properly. Does anyone have any insight? I've heard it could be related to a COMT mutation but I have no idea what that is. Any help would be greatly appreciated, thank you.
     
  2. Valentijn

    Valentijn Senior Member

    Messages:
    14,281
    Likes:
    45,814
    Presumably you haven't been supplementing it at all?

    MTHFR isn't directly involved with B12, so I don't know why MTHFR mutations are a reason for your practitioner to want you to supplement it. MTHFR converts folate from one form to another - if anything, it would be addressed by supplementing a normal dose of folate. Alternatively, studies have shown that eating a diet with a good amount of veggies fully compensates for the risk factors associated with that mutation.
     
  3. seethatlake

    seethatlake

    Messages:
    13
    Likes:
    2
    Australia
    Hi @Valentijn, thanks for your reply. No, I haven't been supplementing with it, not for a long time anyway.
    From what I've read it seems that MTHFR is directly involved with B12 and that you need both methylfolate and methylcobalamin (methylB12) to manage the condition. I do eat a lot of vegetables, especially green leafy ones but it doesn't seem to make a difference. I've had CFS for the past 8 years, and my practitioner seems to think that the methylation stuff is a big part of it. I'm just not entirely sure.
     
    Learner1 likes this.
  4. alicec

    alicec Senior Member

    Messages:
    1,405
    Likes:
    2,716
    Australia
    Do you mean you have elevated results for serum transcobalamin - the bound form of B12 which is taken up into cells?

    If you've not been supplementing B12 this suggests you have a problem getting it into cells. If this is the case you would expect to see signs of functional B12 deficiency - viz elevated MMA and/or homocysteine.

    See this post for more detail.

    B12 and folate certainly do work together and supplementing one can increase the demand for the other. It is often a good idea to supplement together.

    This however wouldn't be affecting you ability to take up B12 into cells.

    Relatively high doses of B12 may be required to drive uptake and overcome whatever aspect of B12 processing/trafficking is sluggish.
     
    seethatlake, Valentijn and Skippa like this.
  5. seethatlake

    seethatlake

    Messages:
    13
    Likes:
    2
    Australia
    Hi @alicec, thanks very much for your reply.

    Yes, I've consistently had elevated holotranscobalamin (active B12, apparently). I don't know a lot about it so I'm not sure if it's the bound version, sorry. I've never done an MMA test but I have repeatedly had low homocysteine. It has only recently increased to a healthier level.

    I have no idea what's going on in my body. It always seems to be a mystery.

    Thanks for posting the link, I'll check it out now.
     
  6. alicec

    alicec Senior Member

    Messages:
    1,405
    Likes:
    2,716
    Australia
    B12 circulates bound to two carriers, haptocorrin, or transcobalamin 1 (about 80% bound B12) and transcobalamin 2 (20%). The transcobalamin 2-B12 complex is known as holotranscobalamin or active B12, since it is the only form taken up into cells.

    Standard B12 blood tests, which measure both bound forms, can be misleading since the amount of active B12 is unknown.

    You however have had the specific test for active B12 so the fact that it is elevated without supplementation does suggest a problem getting B12 into cells.

    It is very interesting though that you have had low homocysteine. Usually when there is a functional deficiency of B12, homocysteine is elevated since methylB12-dependent methionine synthase, which would normally convert it to methionine, is not operating well.

    However other things might affect homocysteine.

    A more specific test for B12 function is MMA. The enzyme methylmalonyl mutase is dependent on adenosylB12 and when it is not functioning well, MMA (methylmalonic acid) accumulates.

    It might be a good idea to get this test ordered to give a bit more insight into what is going on with B12.

    The test is available on Medicare so you just need a friendly GP to order it for you.
     
    Learner1, Helen, seethatlake and 2 others like this.
  7. ryan31337

    ryan31337 Senior Member

    Messages:
    447
    Likes:
    992
    South East, England
    Thanks @alicec for explaining that relationship so clearly.

    I have had consistently elevated serum B12 & Active B12 without supplementation. Some time later I was experiencing B12 deficiency symptoms so threw B12 at the problem without reading up first, unsurprisingly my folate had tanked on the next run of tests as you warn.

    I was able to get a test for MMA requested on NHS from an open-minded consultant, unfortunately it got bounced back by the lab because of the previously elevated serum B12 test that was on record. It would seem that functional deficiency is a dirty word and they prefer to pretend it doesn't exist, so MMA in their eyes is only useful if you have low serum B12...

    In my case many of the things I thought may have been B12 deficiency related were seemingly resolved by managing blood glucose better, but its still something I need to revisit when funds permit.
     
    sb4 and lauluce like this.
  8. seethatlake

    seethatlake

    Messages:
    13
    Likes:
    2
    Australia
    @alicec Thanks again for replying and explaining so many things, I really appreciate your help. My GP is pretty open minded and very accommodating so hopefully he'll be happy to organise the test for me. Awesome that it's covered under Medicare too =] And thanks for sending that article through, it's really interesting.
    Do you know what would cause low homocysteine?
     
    Last edited: Jul 18, 2017
    lauluce likes this.
  9. lauluce

    lauluce as long as you manage to stay alive, there's hope

    Messages:
    394
    Likes:
    649
    argentina
    you´re VERY LUCKY to have a GP so good as yours, my respects to him/her for thinking outside the box
     
  10. lauluce

    lauluce as long as you manage to stay alive, there's hope

    Messages:
    394
    Likes:
    649
    argentina
    PS: I also have consistently high serum b12, but the doctors I can visit don't care about it at all, when tt´s clearly an abnormal result showing some sort of functional deficiency, it´s been in that state for years, if not decades!
    I'm sorry but I can't read much TODAY. Does anybody here has any good links to info about b12 issues, specially high b12? I see many people here are very knowledgeable. I'm from Argentina... I now, poor me :( This is the country that is going to MANUFACTURE AMPLIGEN but isn´t going to prescribe a single pill of it to it's population since MP's don´t know absolutely anything about ME
     
    sb4 likes this.
  11. Eastman

    Eastman Senior Member

    Messages:
    281
    Likes:
    237
    Wonder whether thiamine status has anything to do with this. I posted this excerpt from a Derrick Lonsdale article on another thread:

     
    sb4, seethatlake, Abha and 2 others like this.
  12. alicec

    alicec Senior Member

    Messages:
    1,405
    Likes:
    2,716
    Australia
    An OAT test includes MMA in urine. Genova offers one, also Great Plains Laboratory (GPL) and I imagine there are others. International customers can order the GPL OAT without a doctor. There is a fairly substantial cost of course but it could be something to keep in mind.

    The functional tests can be helpful in confirming that a deficiency exists but the solution is still really empirical - try B12 supplementation, along with a bunch of associated nutrients, especially folate, and see if it helps.
     
    ryan31337 likes this.
  13. alicec

    alicec Senior Member

    Messages:
    1,405
    Likes:
    2,716
    Australia
    Lonsdale's work is fascinating. It is something I've only caught up with recently, prompted by yours and other's posts.

    B12 uptake/processing is very complex and much about it is unknown, however it is certainly an energy dependent process. The critical role of B1 in energy pathways along with Lonsdale's findings of widespread B1 deficiency certainly suggests there could be a link to B12 related problems.

    From a slightly different angle, I can confirm that B12/folate and B1 seem to be intimately connected. Long term B12/folate supplementation appears to have greatly increased my need for B1. I have managed to profoundly deplete B1, despite years of supplementation at what I thought was a more than adequate dose.

    I intend to post on this in more detail on the Refeeding Syndrome thread but am still working out some details.
     
    CedarHome, Learner1, sb4 and 5 others like this.
  14. alicec

    alicec Senior Member

    Messages:
    1,405
    Likes:
    2,716
    Australia
    One possibility is that there is increased use of homocysteine in the trans-sulfuration pathway. This pathway produces cysteine for use in glutathione synthesis and flux through the pathway is increased, for example, during oxidative stress, when demand for glutathione is high.

    The paper I linked about high B12 considers the usefulness of elevated homocysteine as a marker of B12 deficiency and concludes that circumstances of oxidative stress can lower it so serum levels can be misleading. Elevated MMA is not so affected.

    From your original post, it appears that you have come across some of the many claims about the consequences of the presence of common SNPs in various genes.

    You might encounter claims about the C699T SNP in the CBS gene which supposedly leads to a profound upregulation of the gene and hence to greatly increased flux through the trans-sulfuration pathway.

    There is no substance to this claim by Amy Yasko. It is based on a misreading of a research paper which had nothing to do with this SNP. Here is an article which may be helpful if you are concerned about CBS SNPs.
     
    CedarHome and Helen like this.
  15. seethatlake

    seethatlake

    Messages:
    13
    Likes:
    2
    Australia
    @Eastman. Thanks for sending the link, I found the article really interesting. My folate is also elevated so perhaps there is a level of thiamine deficiency and both folate and B12 are simply accumulating because they're not being used.
     
  16. seethatlake

    seethatlake

    Messages:
    13
    Likes:
    2
    Australia
    @alicec Can I ask what your dose of B1 was?

    Thanks again for answering my question about low homocysteine. I've been wondering about it for years but very few people have been able to comment. I did find this article a while ago though which is great;

    http://www.drkendalstewart.com/wp-c...9/Significance-of-Low-Plasma-Homocysteine.pdf

    I read the article about the CBS SNP's too and it's comforting to know that even if I do have that it shouldn't be of great concern. Thanks again.
     
  17. alicec

    alicec Senior Member

    Messages:
    1,405
    Likes:
    2,716
    Australia
    For years I took 50 mg allithiamine daily.

    If you read the Refeeding Syndrome thread linked above by @Eastman, you will appreciate the phenomenon of depletion of subsidiary nutrients which can interfere with the beneficial effect of B12/folate.

    Folate, potassium and various trace minerals seem to be the most common, and I certainly experienced this at times, later I found that I seem to have depleted several B vitamins.

    Most recently I have been trying to track down what else is missing since again the beneficial effect of B12/folate has been petering out. I suspected B1 (despite the experiences of Freddd, the original poster on the Syndrome and indeed on the whole active B12 protocol, who found that too much B1 increased the need for folate) but increasing my dose of allithiamine was intolerable.

    Eventually I experimented with adding a different form benfotiamine (continuing the 50 mg allithiamine). This was a revelation.

    Initial repletion can involve very large doses which can later be tapered off. One needs to experiment to find out the dose beyond which more makes no difference.

    Initially I lost track of how much much benfotiamine I took - I just kept taking several hundred mg every couple of hours as long as I continued to get a positive response (increased energy, less brain fog, great improvement in eye irritation/blurring symptoms). Eventually I have settled on 500 mg benfotiamine 3 x daily.

    I think a significant portion of this dose is actually wasted - ie the thiamine transporter has relatively slow uptake, but this large dose seems necessary to drive sufficient uptake to affect my symptoms.

    I may adjust this dose again and eventually (after several more months) I plan on reducing it substantially, hopefully having repleted what seems to be an incredible B1 deficit.

    It's all very much an individual thing that needs to be worked out by trial and error.
     
    CedarHome, sb4, Gondwanaland and 3 others like this.
  18. Eastman

    Eastman Senior Member

    Messages:
    281
    Likes:
    237
    That's a huge amount. What do you think is the next thing that's likely to be depleted? Other than the usual list of magnesium, potassium and phosphorus, I'm thinking of B3, especially with all the methyl groups being generated from the methylation protocol.
     
    sb4 and Gondwanaland like this.
  19. alicec

    alicec Senior Member

    Messages:
    1,405
    Likes:
    2,716
    Australia
    Yes it is a huge amount but I seemed to need that much to get maximum beneficial effect. I have already halved this dose and anticipate reducing more in the near future.

    I'm sure much of the dose was being wasted but the amount seemed necessary to maybe drive maximun possible uptake - I'm not sure.

    I'd hate to guess about what might be the next thing to be depleted - acutally I'm kind of hoping I might have come to the end of the line.

    It seems a very individual thing, possibly reflecting individual variation in blocked metabolic pathways, as described by Naviaux.
     
    sb4 and Eastman like this.
  20. MogMog

    MogMog

    Messages:
    14
    Likes:
    9
    I've just been tested too and have high active B12, 239 pmol/L (range 25 - 165) despite not taking B12 supplements. Red cell folate was 550 nmol/L (range 285 - 1474). I have slightly raised homocysteine (11 umol/Ls) and have never tested MMA. The several occasions I've taken B12 it seemed to have a bad effect on me.
    So, if I'm understanding correctly, I should be taking B12, despite my high active B12 result?
    Should I get MMA tested?
     

See more popular forum discussions.

Share This Page