Pyridoxine Is Toxic And Inhibit P5P Function?

Discussion in 'B6' started by André Luiz, Dec 23, 2018.

  1. André Luiz

    André Luiz Member

    Joined:
    Sep 25, 2017
    Messages:
    116
    Gender:
    Male
    The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function. - PubMed - NCBI

    ↓ Full text
    The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function.
    Vrolijk MF, et al. Toxicol In Vitro. 2017.
    Show full citation
    Abstract
    Vitamin B6 is a water-soluble vitamin that functions as a coenzyme in many reactions involved in amino acid, carbohydrates and lipid metabolism. Since 2014, >50 cases of sensory neuronal pain due to vitamin B6 supplementation were reported. Up to now, the mechanism of this toxicity is enigmatic and the contribution of the various B6 vitamers to this toxicity is largely unknown. In the present study, the neurotoxicity of the different forms of vitamin B6 is tested on SHSY5Y and CaCo-2 cells. Cells were exposed to pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5-phosphate or pyridoxamine-5-phosphate for 24h, after which cell viability was measured using the MTT assay. The expression of Bax and caspase-8 was tested after the 24h exposure. The effect of the vitamers on two pyridoxal-5-phosphate dependent enzymes was also tested. Pyridoxine induced cell death in a concentration-dependent way in SHSY5Y cells. The other vitamers did not affect cell viability. Pyridoxine significantly increased the expression of Bax and caspase-8. Moreover, both pyridoxal-5-phosphate dependent enzymes were inhibited by pyridoxine. In conclusion, the present study indicates that the neuropathy observed after taking a relatively high dose of vitamin B6 supplements is due to pyridoxine. The inactive form pyridoxine competitively inhibits the active pyridoxal-5'-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency.
     
  2. haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,431
    Gender:
    Male
    Location:
    USA / Europe
    Yep. And the older the person the less pyridoxine they are able to convert into P5P. That's one of the main reasons we use P5P in our Energin and not the pyrodoxine Hcl. The latter will probably work OK in people under 30 but its (neuro)toxicity becomes rather obvious with advancing age and in doses higher than 25mg daily.
     
  3. Steven Bussinger

    Steven Bussinger Member

    Joined:
    Oct 8, 2016
    Messages:
    266
    Gender:
    Male
    Location:
    Colorado, USA
    Crepes, I'll have to get P5P next time, then. I take Energin in the day, but use 100mg pyridoxine HCL before bed.
     
  4. sunraiser

    sunraiser Member

    Joined:
    Feb 21, 2017
    Messages:
    482
    I think it's an extreme amount to be taking each day, but to each his own. The following quote is from this paper:

    http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/760.pdf

    Basically it would suggest that p5p has to be dephosphorylated before intestinal absorption regardless, so it's likely to have far lower bioavailability. This would very likely account for the perceived "lack" of toxicity as it simply wouldn't be being absorbed to large degrees in many people.

    HOWEVER, I have read that people with leaky gut may technically miss this step as some might be absorbed before it reaches the intestines and it can provide them benefit for a temporary time (as p5p). Also just to note I have read experiences of people getting severe peripheral neuropathy from p5p as well as B6 (Hcl), so it's not to say it's completely inert.

    It's also possible there's some metabolic need for the phosphorylation step of B6 and that it's not simply making it bioavailable, but it's doing something else that has a physiological purpose.

    It isn't as black and white as this post makes out, that's all I know.

    Again, I can't fathom 100mg per day being a sustainable intake, but you obviously have your own internal compass and experiences to guide you.
     
  5. Steven Bussinger

    Steven Bussinger Member

    Joined:
    Oct 8, 2016
    Messages:
    266
    Gender:
    Male
    Location:
    Colorado, USA
    That's what a single capsule is, 100mg. I guess it is a lot, since it's 500x the RDI. I'll order a better supplement.
     
  6. sunraiser

    sunraiser Member

    Joined:
    Feb 21, 2017
    Messages:
    482
    You could just cut up your tablet. Maybe take half a pill every 7 days, or half the capsule contents.

    It'd put things in a much more reasonable range. You'll be able to judge your experience and need better than my guess work ever can, though!
     
  7. Antonello

    Antonello Member

    Joined:
    Jul 22, 2017
    Messages:
    277
    Gender:
    Male
    Location:
    Italy
    @haidut I'm wondering if this study on plain version of B6 can replicate what happen with B2 as I'm noticing two completely different effects from the plain riboflavin and the R5P.
     
  8. haidut

    haidut Member

    Joined:
    Mar 18, 2013
    Messages:
    16,431
    Gender:
    Male
    Location:
    USA / Europe
    Yes, the same is known to happen for riboflavin Hcl. Both B2 and B6 in their Hcl form can be toxic in higher amounts due to lack of conversion into the phosphorylated forms. The issue becomes more and more pertinent with advancing age or illness, as phosphorylation of both pro-vitamins depends on ATP, which is obviously low when somebody is older/sicker.
    Pyridoxal kinase - Wikipedia
     
  9. GreekDemiGod

    GreekDemiGod Member

    Joined:
    Aug 9, 2019
    Messages:
    131
    Gender:
    Male
    Started taking pyridoxine 8 mg / day. You guys think it's too high of a dose?
     
  10. Max23

    Max23 Member

    Joined:
    Jun 11, 2018
    Messages:
    55
    Gender:
    Male
    That is a very low dose. I doubt it´ll have any effects. I didn´t have much effects from 50. When I increaseed it to 150 I got great results, which seem to be fading after ten days or so. Looking for to get P5P and riboflavin.
     
  11. charlie

    charlie The Law & Order Admin

    Joined:
    Jan 4, 2012
    Messages:
    10,868
    Gender:
    Male
    Location:
    USA
    I think it was Dr. Lonsdale who said the B6 toxicities are actually B1 deficiency because B6 depletes B1.
     
Loading...