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Started taking B6 and feeling funny. Help Please. :(

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by boo85, Dec 1, 2014.

  1. alicec

    alicec Senior Member

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    This question of what high P5P in blood actually means is very interesting - it could mean that too much B6 is being ingested and hence that neurotoxicity is likely, or it could mean too little is being taken up by cells and thus that a functional deficiency is likely.

    How do you tell the difference? I've tried to read up on this (when my worsening brain fog allows) and have concluded that there is far too little research and it can only be determined empirically, although an OAT test would give some insight into a likely functional deficiency. A P5P test by itself means very little.

    The neurotoxicity literature was particularly disappointing. There really are only a few studies which showed that high levels of P5P tended to be associated with neurotoxicity but not necessarily, and nothing much about mechanism.

    There is a secondary issue of which form of supplementary vitamin to take - is P5P better or somehow more protective from neurotoxicity?

    As @MacGyver notes, for P5P in the blood to be taken into cells, alkaline phosphatase is necessary to remove the phosphate group because the B6 transporter carries only the unphosphorylated form. Once inside the cell, a kinase enzyme puts the phosphate group back thus making the active vitamin again inside the cell (where it stays since the transporter won't carry it out with a phosphate present).

    Before this, in the gut, AP activity is also necessary to allow phosphorylated forms of the vitamin from food and supplements to be absorbed. The liver then makes the active phosphorylated P5P and dumps it into the blood where it is available for uptake by cells, after appropriate processing.

    You might ask what then is the point of taking expensive active B6 supplements since the body has to remove the phosphate before they can be used. Well, the story is a bit more complicated because it appears that there is at least some direct uptake of the phosphorylated form of the vitamin, probably by endocytosis. Also it appears (though there is not a lot of good evidence for this) that P5P supplements might be 5 times more active, weight for weight, than the more usual pyridoxine supplements.

    So how a person responds to B6 supplementation, whether P5P or pyridoxine or some combination thereof, is the result of their own individual combination of direct P5P endocytotic capacity as well as phosphatase and kinase activities.

    One or the other form is not necessarily better, it all depends on the individual and can only be determined empirically.

    Getting back to the basic issue of what high plasma P5P means, as I mentioned in my post a few months ago, in light of some of the info in this thread I decided to do some experimenting with B6. I can now report that, despite my high P5P, reducing B6 has not been a good idea. I think I definitely fall into category where it means functional deficiency. An OAT test also shows deteriorating oxalate markers and elevated kynurenic acid, both B6 related.

    Interestingly, as time has gone by I have found myself become intolerant of magnesium (in my case nothing to do with boron since I have continued to take a trace mineral supplement containing 0.7 mg boron daily) as well as methyl folate and methyl B12 and have had to reduce my intake of all considerably.

    I can't necessarily attribute this to an increasing functional B6 deficiency since my overall condition has been deteriorating since before I started experimenting with B6 (the decline was of course part of the reason I was casting around for different things to experiment with) but the coincidence seems very suspicious to me.

    I am going to start increasing B6 again.
     
    Last edited: Dec 26, 2015
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  2. MacGyver

    MacGyver

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    My own idea and thus opinion on pyridoxine (B6) causing issues but not P5P is that pyridoxine needs to go through a few conversion steps before it becomes P5P. Hence if you start supplementing with it in very high doses you'll be depleting other things, especially B2. So what is currently being explained as 'pyridoxine causes neuropathy' should actually be 'pyridoxine induces a deficiency in X, Y and Z because X,Y and Z are necessary for pyridoxine to do its job'. And a deficiency in X,Y and Z causes said issues. One thing I can't explain with that is that some people have had success in resolving their B6 issues by taking B12. Since B6 works together with B12 to do its job I presume they were inducing a B12 deficiency.

    I've got a personal beef with the current common mindset of agonists/antagonists and X will deplete Y so watch out! Its such a negative way of thinking that it doesn't make sense to me, its too simplistic as well. Even though I'm struggling with it I'm in awe with how complex the human body is and I can only be humble and have huge respect for it. It demands our respect.

    @alicec Well, I'm currently on 6mg of boron so I wouldn't rule out boron at 0,7mg yet. All studies start at 3mg and go up to 10mg.
    Once I found out I could take magnesium when I took 6mg boron I had to up my intake of B2 (and B6). Since boron works together with B2 in the liver to do its job. And there's more:
    We know boron raises RBC magnesium levels. We know P5P needs to be inside cells to pull in magnesium. We know alkaline phosphatase is needed to get P5P inside cells (this is where boron comes in as it impacts alkaline phosphatase). We know that B2 is needed to convert pyridoxine to P5P. So this means boron will increase the need for B2 and B6! Makes more sense and sounds a lot nicer than 'watch out with boron! It can cause a B2 deficiency! So don't take too much boron!' don't you think? :) You'll pee out excess boron anyway.

    If I were you I'd try the following combo: start by increasing your intake of B2 and B6, but slowly, check out the 'B2 I love you thread' with regards to iron and manganese (this is what I very probably need to take more of now). Increase your boron intake to 3 or 6mg. Up your intake of B6 and B2. If you do it in that order you'll start to notice magnesium deficiency symptoms anyway! Eyelid twitching, cramps etc.

    I'll post what works for me but that is only a guideline; you'll need to empirically figure out your own dosages obviously. And you might encounter other deficiencies than me that block progress.
    I take 6mg of boron (NOW Foods 3mg) each day. For each increase of 125mg of magnesium (from Jigsaw Health's Basic package) I have to take 50mg P5P (Solgar) and 25mg B2 (Solgar 50mg/2 Riboflavine). Additionally I have to add the occasional (2 or 3 times a day) extra B2 which I currently do in FMN form (Source Naturals 25mg FMN yielding 18mg R5P).

    With this combo I was able to reach 750mg of magnesium but I'm currently running into a manganese defiency because of the B2 healing my liver from its iron overload. So I'm backing down again until I can ramp that up (there's already 2mg manganese in that Jigsaw Basic package but that's obviously not enough)

    Good luck!

    I'm sure we'll figure all this crap out sooner rather than later. I already have some interesting ideas for some helpful software to make more sense of this supplement maze but I first need to resolve my own issues before I can start on that :)
     
    Last edited: Jan 2, 2016
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  3. Richard7

    Richard7 Senior Member

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    I cannot add any information, but I just thought I might say that this really is a case of trying to lift ourselves by our own bootstraps isn't it.

    We have to grab a moment of clarity to try to understand the science, and then to intervene to try to create more moments of clarity in which we can better understand the science.

    And I'm not in a moment of clarity, just a bit of insomnia and energy after a day in which I was mostly in bed.

    I hope your n=1 experiments work.
     
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  4. alicec

    alicec Senior Member

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    Currently I can't figure out what has happened to me over the past few months but thanks for your suggestions - I'll rethink things in light of these. Something has become very unbalanced.

    I used to happily take 600-800 mg magnesium (as bisglycinate) orally plus a 4-5 ml magnesium chloride topically - had done for years - now I've had to drop all of the oral dose though have continued the topical.

    It certainly feels to me that I have slowly depleted something but I can't figure out exactly what. Certainly I'll try more boron - I have some of the 3 mg stuff which I took for a while a long time ago. I've been taking 50 mg riboflavin (or 35 mg riboflavin 5 phosphate) daily for a very long time, the trace mineral prep contains 2.5 mg manganese and 50 mg pyridoxal 5 phosphate has been a minimum dose of B6 for some time (I have added considerably more as pyridoxine at times as a way of dealing with oxalate problems).

    I only stopped the B6 completely for a short time - it became clear quickly that this was not a good idea and for now I am back to 50 mg P5P. While I had to reduce the methyl folate and B12 considerably it seems too that this is not a good idea and I am trying to increase very slowly (I once used to tolerate quite high doses).

    Have to do more experimenting!
     
  5. MacGyver

    MacGyver

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    Indeed, it's a terrible disgrace that we have to figure this out ourselves but I guess that goes to show how our human 'culture' works and how far we have come in terms of 'civilization'...
    Anyway, preaching to the choir here and we've got better things to spend our energy on :)

    Once my situation improves further I hope I can create something that can take a lot of this effort away by bundling a lot of the info that is available into a tool that provides hints on what supplements to try next based on personal info/symptoms, why those, warn of adverse effects and possible induced deficiencies etc. While the overal symptom set of each person is unique, something that has become evident to me is that you can break it down into different parts and those appear to be quite similar between different people and they respond similarly to certain supplements. Sometimes with 3 different possible responses but still the same. I'm probably oversimplifying it but it seems like you can create quite simple flow charts with taking each supplement and see how you respond.
    Anyway, future plans...enough of those ;)

    Well the baseline on which I still was unable to take any magnesium is my Jigsaw Health Basic package (I'm mentioning it specifically because if you go and look up what's in it you'll notice its quite complete except for boron(!) and calcium (still don't appear to have an extra need for that btw)) which contains 25mg R5P as well as 25mg P5P. I tried a lot of different things on top of it but only when taking boron could I take magnesium, albeit only shortly. Then I figured out I needed to take additional B2 and B6 along with the boron to be able to take magnesium.
    Like I said earlier I then ran into issues with the B2 causing light orange stool, insomnia, fatigue etc.. Just started on additional manganese to see if that is the solution for that :) It just might be the case I have to wait and let my body do its thing but I'm too impatient for that and I continue experimenting. Not like I have another choice anyway!
     
  6. Beagle

    Beagle

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    Very happy to help out; I'm a software engineer by trade and have been thinking of ways to collate the huge amount of useful information (including contradictions) and present it in a more organised and easily digestible format than various forum posts and web pages. It'd be really interesting to look for patterns too, and to get longer-term feedback from people (how many times do we go "Oh wow, this works!" and 2 weeks later it's doing nothing/the opposite?)
     
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  7. alicec

    alicec Senior Member

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    @MacGyver there is certainly something to the boron and riboflavin. I have made a post about my experiences so far (in a slightly different context) here.
     
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  8. MacGyver

    MacGyver

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    Very cool! :) That reinforces my belief that I am making correct assumptions with regards to boron-B2-B6-magnesium :)

    Small update on my own journey: I've tried adding additional manganese (10mg/day total) to see if that helped with my other issues but results so far are inconclusive.
    Something else I've tried is upping my P5P/B2 intake while not increasing my magnesium intake; that leads to feelings of anger and a certain anxious/tense feeling along with some eyelid twitching which are all resolved quite quickly by taking magnesium. So it's obvious that what is working for me is the actual combination of B6 and magnesium (on top of boron) and neither of them alone. That leads me back to B2 and its issues as well as insomnia and feeling very tired as being the limiting factors of being able to up my magnesium intake. Back to the drawing board!
    Current plan: stabilizing the B2-B6-magnesium combo to something that doesn't overload my liver (which I had again on Saturday after loading too much B2 on Friday) Oh how hard it is to not take too much B2 when I feel so great with it. :p Only after that is working for at least a week can I try the manganese again.

    Like Freddd likes to say: when walking through hell, keep walking!
     
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  9. dannybex

    dannybex Senior Member

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    This is anecdotal of course, but this person ("Standing Up") got rid of her b6 toxicity by taking huge amounts of B12, so the b6 inducing B12 deficiency might be true for some:

    http://www.longecity.org/forum/topic/57584-b6-toxicity-from-p-5-p/

    You may not need supplemental magnesium if your body is rejecting it. If epsom salts are helping, then maybe the missing piece of the puzzle in your case is more sulfate?
     
  10. Johnmac

    Johnmac Senior Member

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    Just a wild card: you're not taking any form of carnitine are you? The above matches symptoms of carnitine overdose quite well.
     
  11. dannybex

    dannybex Senior Member

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    Just an FYI -- perhaps the bisglycinate may have been why you didn't tolerate it. Quite a few folks have experienced worsening oxalate issues with glycine or foods high in glycine, like gelatin.
     
  12. alicec

    alicec Senior Member

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    I doubt that that is the reason. I have been taking the bisglycinate form for years, since long before I came to understand that oxalates were an issue for me. The sensitivity arose well after I had taken various measures to reduce my oxalate load and when OAT values were markedly improved - in other words when oxalates were no longer such a problem.

    I did try experimenting with the only other form of magnesium that I tolerate - viz magnesium chloride - but seemed to have the same problem so I concluded that it was the magnesium that was now the issue.

    I've finally got around to organising some tests of various plasma and RBC minerals next week. Maybe I might get some insight into what is going wrong - but maybe not!
     
  13. dannybex

    dannybex Senior Member

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    @alicec Just curious if you had high quinolinic levels? I'm assuming that your glycolic was high, thus the suggestion to take B6 in the first place, to lower endogenous oxalate production?
     
  14. alicec

    alicec Senior Member

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    No, quinolinic has never been elevated. Kynurenic was before I started addressing oxalate and B6 issues.

    Glycolic, glyceric and oxalate have all been elevated to various degrees. Sometimes oxalate still is (I think this is probably a good thing - getting rid of oxalate stores) though glycolic and glyceric have normalised.
     
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  15. dannybex

    dannybex Senior Member

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    Okay, thanks. That's good to hear, and interesting. My kynurenic was within the normal range, but quinolinic was elevated. I don't quite understand why Owens recommends b6 for both 'k' and 'q', since if I'm reading the studies correctly (which is a BIG 'if') then when sufficient niacin is present, then there's no need to for tryptophan to be broken down to make niacin, the process of which results in elevated levels of both metabolites.

    Anyway, I've been asking a lot of questions over on the TLO group on FB, and trying to figure this out as I've lost so much muscle and can't tolerate either b6 or p5p, even though I thought b2 was helping for a bit.
     
  16. alicec

    alicec Senior Member

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    Perhaps because many B6 dependant enzymes are involved in the q pathway.
     
  17. alicec

    alicec Senior Member

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    I'm not sure what studies you are referring to but as I understand it, the vast majority of tryptophan metabolism normally proceeds down the kynurenine pathway. Only a small proportion travels down the serotonin pathway. In other words production of kynurenic and quinolinic etc happens all the time and is not dependent on availability of niacin.

    Kynurenic becomes elevated which B6 deficiency causes blockages further downstream, allowing this metabolite to back-up (it is a side-arm of the kynurenine pathway).

    Elevated quinolinic has more complex causes, but can involve stress and inflammatory conditions activating a rate-limiting enzyme and increasing flux through the whole pathway.
     
  18. dannybex

    dannybex Senior Member

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    Yes, good points. But also it's elevated when niacin is deficient. Quoting this study, if there is "sufficient niacin content in the diet, little quinolinate production is required in the liver, and the concentration of quinolinate and other kynurenine pathway metabolites in tissues and blood is low."

    So I would say that if one is getting enough niacin then there would be less worries over quinolinic, as tryptophan wouldn't be needed to be broken down in order to make enough b3 in the first place -- so that kynurenic also becomes elevated as a result of b3-deficiency.

    And in rats, it was elevated in B12 deficiency.

    And folic acid protected against quinolinic toxicity at least in chick retinal neurons.

    As for the b6-quinolinic issue: I can't find the study right at the moment, but it was a case study on siblings, and I took a screen cap which said the following:

    "The QA excretions in both the sibs were greater when they were receiving normal amounts of pyridoxine than when they were receiving the pyridoxine supplements."

    My foggy brained interpretation of that suggests that b-6 supplementation increases retention of quinolinic acid.
    And perhaps that's why some of us cannot tolerate b6 in any supplementary form, because it inhibits excretion of the toxin.
     
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  19. alethea

    alethea

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    Alicec: You need potassium. It's required for B6 to be assimilated. Low K could also be making you intolerant of magnesium because your K:Mg is already off. Also methylation (which is increased by methylfolate and methylB12) will increase potassium needs. Google "Potassium, Your Invisible Friend" by Dr. Malcolm Kendrick and try taking 1/4 tsp potassium chloride several times throughout the day. I sometimes take about 7 of them. There is a lot of fear-mongering in the US about supplemental potassium, but it's actually one of the things most lacking among the chronically ill.

    Low K means the body is constantly short on B6 (B6 balances Na and K -- very crucial for survival) and is unable to conduct all the B6-related activities, which include blood sugar regulation, oxalate metabolism, neurotransmitter synthesis, heme synthesis (--> pyroluria), fatty acid metabolism, hormone metabolism, amino acid synthesis, DNA and RNA synthesis, etc., etc. Low K is what Gerson was essentially addressing.

    Low K is also implicated in autism (//hypokalemic sensory overstimulation) and oxalates problems, which are increased endogenously by low B6 (oxalates problems will also disrupt sulfation). It's also implicated in ME/CFS, where the sensitivity to mold is related to the fact that the body is already full of tissue oxalates because of the low B6 because of the low potassium. Na-K balance has implications for pH (Na increases acidity, K alkalinity), and under conditions of extreme low B6/low K the body will resist anything that increases acidity, not just exercise (lactic acid), but ultimately even cellular respiration. It will also be supersensitive to stimuli (again, hypokalemic sensory overstimulation).

    Interestingly, as time has gone by I have found myself become intolerant of magnesium (in my case nothing to do with boron since I have continued to take a trace mineral supplement containing 0.7 mg boron daily) as well as methyl folate and methyl B12 and have had to reduce my intake of all considerably.

    I can't necessarily attribute this to an increasing functional B6 deficiency since my overall condition has been deteriorating since before I started experimenting with B6 (the decline was of course part of the reason I was casting around for different things to experiment with) but the coincidence seems very suspicious to me.

    I am going to start increasing B6 again.[/QUOTE]
     
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  20. alicec

    alicec Senior Member

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    No I don't.

    I have supplemented potassium in the past and it was helpful but gradually I began to get the gut irritation associated with too high a dose from even small doses. I stopped and was fine without it.

    Blood potassium levels coincide with my body's different response to potassium. It has gone from low normal to high normal and remained there.

    It was calcium that enabled me to tolerate magnesium again and various trace minerals and biotin that helped me to tolerate B12 again.
     
    Last edited: May 7, 2017

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