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Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Gondwanaland, Aug 5, 2017.

  1. Gondwanaland

    Gondwanaland Senior Member

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    https://www.ncbi.nlm.nih.gov/m/pubmed/28716455/
     
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  2. Asklipia

    Asklipia Senior Member

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    Very good find! :thumbsup:
     
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  3. alicec

    alicec Senior Member

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    Yes very interesting find.
     
  4. aquariusgirl

    aquariusgirl Senior Member

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    Damn I do better in B6 than in P5p .....what's the threshold for inhibiting those other enzymes?
     
  5. liverock

    liverock Senior Member

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    From the introduction to the study it appears that they are trying to imply that the neurological pain that was suffered was due to high pyroxidine buildup due to pyroxidine in effect lowering P5P the active form of B6.

    This test was an in vitro study, In practice(not a lab test) high serum pyridoxine and low P5P levels are quite often due to the MTHFR gene mutations. Increasing folate and B12 will increase methylation and conversion of pyridoxine to P5P to solve the problem.

    http://www.side-effects-site.com/vitamin-b6-side-effects.html
     
  6. bertiedog

    bertiedog Senior Member

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    Would anybody have a view as to whether 50 mg daily of this vitamin could play a part in causing severe migraines? I have been trying to work out what could be causing my problems and hadn't realised I was taking such a high dose?

    Pam
     
  7. Gondwanaland

    Gondwanaland Senior Member

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    Yes, I had that with P5P. I assume it is serotonin build up (= B2 deficiency)
    Thanks for that. This explains why the in vitro study perfectly matches my experience. When I first started taking B vits I would always get symptoms of B6 deficiency no matter how high or low my B6 intake was. It was only when I took P5P that I felt how a healthy B6 metabolism feels. B12 and folate cause me B1 deficiency.
    I suppose your body will tell you.
     
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  8. alicec

    alicec Senior Member

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    I read the article you linked. It is nonsense. The MTHFR gene does NOT
    The gene codes for an enzyme which converts 5,10 methylene THF to methyl THF - so yes it does create ONE of the active forms of folate, but it does not act on folic acid.

    MethylTHF does in turn replenish the methyl group on methylB12 used in the methionine synthase reaction, so indirectly, yes, MTHFR is important for B12 function.

    Activation of B6, however, involves phosphorylation (addition of a phosphate group), not methylation. It has nothing to do with MTHFR.
     
  9. Gondwanaland

    Gondwanaland Senior Member

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    I do not question that, but I suppose that the methylation cycle gears in the urea cycle, so could it be an indirect activation?

    Choline is a methyl donor ("system input") and it increases the need for B2 ("system output").
     
  10. liverock

    liverock Senior Member

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    Thanks for the extra information. I just take folate and B12 when I get a build up of pyroxidine which for me seems to go hand in hand with low B12 symptoms.
     
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  11. alicec

    alicec Senior Member

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    Sorry - I don't follow the links. What is the connection between methylation and the urea cycle and what in turn does the urea cycle have to do with B6 activation?

    Sorry again I don't follow the connection. Do you mean that anything which stimulates methylation will increase need for B2 and that this in turn might affect B6 activation (adversely) since B2 is required in this process?

    Even if this were the case, and I'm not sure that it is, the article is saying the opposite - it claims increasing methylation will increase activation of B6.
     
  12. Gondwanaland

    Gondwanaland Senior Member

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  13. Asklipia

    Asklipia Senior Member

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    :thumbsup:
    Acetaldehyde is detoxified by B1, is it not? Subsequently inducing Thiamine Deficiency.
    Maybe this is how taking a lot of thiamine has boosted my B6 levels (seen by increased dreaming).
    Nice to start the day with a puzzle solved!:)
     
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  14. Gondwanaland

    Gondwanaland Senior Member

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    + Molybdenum

    I have run into problems with P5P only, and now I understand this recommendation:
    ETA
     
    Last edited: Dec 12, 2017
  15. Bluelude1

    Bluelude1

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    Does this mean that people with high B6 levels / MTHFR should opt for P5P exclusively or use it in conjunction with Pyridoxine HCL?

    Currently, I take 1000mg Pyridoxine HCL & 100mg P5P, but I've been trying to get to the bottom of whats causing such a high dose requirement to mitigate deficiency symptoms. I find if it's not handling symptoms some days I've tried additional Pyridoxine HCL, but I promptly end up with neuropathy and restless legs every time. My dad is at the exact same dose and swears taking an additional 50mg of P5P (150mg total a day) does a better job.

    We try not to go over 100mg P5P a day because that's supposedly the safe limit, but this thread has me wondering if there is more to the story.
     
  16. alicec

    alicec Senior Member

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    It suggests that pyridoxal forms of the vitamin (as far as I know only pyridoxal 5 phosphate is available) are the best option for everyone, but particularly for people who have high needs.

    MTHFR has nothing to do with B6.

    Based on what?

    The study suggests your father's observation are worth following up. Have you ever tried ditching the pyridoxine altogether? Maybe it is the cause of your problems since it can compete with the active vitamin.
     
  17. Bluelude1

    Bluelude1

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    That's just the amount I've heard repeatedly not to exceed of P5P. Not sure what the "real" limit is.

    I haven't until I ran across this thread, but I am planning to make the change immediately and see what happens.
     
  18. JES

    JES Senior Member

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    The number one safety issue from excessive B6 is nerve damage, but this only applies to regular B6, AFAIK P5P does not have this side effect, so if anything it should be safer to exceed the dosage with it. The one thing to keep in mind is that P5P is more concentrated than regular B6. I notice a serotonin kick from much smaller dosages of P5P than B6, which makes me sleepy etc. So probably you want to take at least five times less P5P than normal B6.
     
  19. Bluelude1

    Bluelude1

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    Wouldn't you have to still be mindful considering its the active form and wouldn't have the same rate limiting protections that Pyridoxine HCL would have?

    Apparently P5P is 5x more potent then B6
     
  20. JES

    JES Senior Member

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    The user reports and conventional wisdom over the Internet suggests that P5P would not have this side effect. However, remember that this is only anecdotal evidence, I doubt any medical studies has been done comparing B6 to P5P. I found one case online where a person reported the same neuropathy side efffect from P5P (source). I guess the likelihood of this is down to genetics as well. I could never get near those dosages anyway.
     

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