B6 deficiency and intolerance

Inara

Inara

Senior Member (Voting Rights)
Hi everyone!

I have vitamin B6 deficiency whilst blood levels are normal/elevated (even without substitution) and I cannot substitute B6 due to intolerance (even small amounts lead to trembling and higher heart rate). I have also low alkaline phosphatase. Has anyone an idea what this could be and how it could be overcome? I already did long searches, but I cannot find the answer. I also tried several things (taurine, B2; Zinc and magnesium are standard). No change. I do have magnesium deficiency but supplement it.

Any ideas?
 
Elevated blood B6 without supplementation suggests there is a problem getting the B6 into cells.

I haven't seen any research on this, apart from studies of very serious in born errors of metabolism, where for example, in the condition hyphosphatasia, there is elevated serum B6.

The reason for this is that most B6 circulates in the phosphorylated form but this can only be taken up into cells if the phosphate group is clipped off by tissue non-specific alkaline phosphatase (TNSALP), present on the surface of cells. In hypophosphatasia, TNSALP is defective, sometimes non-functional.

I'm not suggesting you have hypophosphatasia. This is a very serious condition and if you had it you would certainly know by now if indeed you had survived to adulthood.

However in the absence of research on mild and presumably acquired conditions which might be similar it does give us some clues.

You say you have low alkaline phosphatase. This blood test does at least in part reflect TNSALP activity so it could be part of the reason for your problem.

What to do about is more difficult in that there is not much to go on.

At least some forms of hyphosphatasia are responsive to B6 and this is a very important part of the treatment. You say you can't tolerate B6. There are lots of anecdotal reports of B6 sensitivity. There may be many reasons for it but often it is because something else that is needed in B6 processing and activity is missing.

You might need to experiment with supply of B vitamins in general before trying B6 again. Maybe look for things that others have found helpful in overcoming B6 sensitivity. I don't think you will find much actual study of the problem.

Maybe the form of B6 is a problem. I have seen a study suggesting that the pyridoxine form (the most common B6 supplement) can be problematic in some people. Pyridoxal 5 phosphate might be worth considering. Probably most of the phosphate group on the supplement will be cleaved off in the intestine but the pyridoxal remnant may be easier for you to deal with.

The other thing to consider is that the TNSALP enzyme uses zinc and magnesium as cofactors. You say you have been supplementing them but maybe you need more. Sometimes if enzymes are sluggish you might need large amounts of cofactor to stimulate them.

Sorry I can't be more helpful but this is something to be going on with.

ETA I forgot to say I did a quick google for low serum alkaline phosphatase. Found a study which found the most cases followed things like cardiac surgery, but other significant causes were magnesium deficiency, hypothyroidism and anaemia.
 
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Hi @alec,

Thank you so much for answering!

My low alkaline phosphotase levels were suggestive for hypophosphatasia, but this was ruled out. My levels remain low; in fact, over the years, they decreased further, even though I supplement Mg and zinc.

My searches (and laboratory results) led me, too, to the problem that B6 can't be transported into the cell - due to low alkaline phosphatase. I am relieved you confirm this (I am no biochemical expert). Or maybe a needed binding protein is missing?

I looked at a lot of papers. I only find this problem in the context of hypophospatasia. I guess that maybe there is a mutation in the ALPL gene that leads to minor problems and which isn't known or wasn't checked for.

Maybe I should go into the link between TNSALP and ALP.
 
I was supplementing P5P. I never tried the non-phosphorilated B6 versions (like pyridoxine). Maybe I should? I tried taking P5P and Riboflavin (phosphorilated) in a certain ratio due to someone's personal experiments, but still reacted to B6. I have no problem with B2 alone or the other ("activated" B vitamins). I take Folate and some other B vitamins, too.

alicec said:
Probably most of the phosphate group on the supplement will be cleaved off in the intestine but the pyridoxal remnant may be easier for you to deal with.
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That's what I found, too, and wondered why to take P5P if the phosphorous is split off in the intestine when passing the gut mucosa. Here's the answer. Thanks! :)
 
alicec said:
ETA I forgot to say I did a quick google for low serum alkaline phosphatase. Found a study which found the most cases followed things like cardiac surgery, but other significant causes were magnesium deficiency, hypothyroidism and anaemia.
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I take around 1400mg of magnesium compounds daily. I can try to go higher.
Anaemia shouldn't be present, but to be honest, I don't know for 100%. My laboratory results are always dismissed as okay even if some are out of "normal bounds".

But shouldn't rise ALP with magnesium and zinc intake if the low levels are due to mg and/or zinc deficiency?
 
Inara said:
Hi @alicec,
do you maybe know if something like a malabsorption of mitochondria exists?
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Do you mean malabsorption of B6 into mitochondria?

I don't know anything about this so did a quick google. All I could find was this old paper which found the following:-

Approx 20% B6 in liver is in mitochondria.

Mostly it is present as phosphorylated forms associated with the inner membrane-matrix complex.

It is mostly associated with aminotransferase enzymes.

Kinases are not present in the mitochondrion so the phosphylated B6 forms are carried into the mitochondrion from the cytosol.

At the time of the study, nothing was known of this transport mechanism.

My recent google didn't find anything either.
 
Inara said:
What about malabsorption of mitochondria in general?
Click to expand...

I'm not sure what you mean by this. If you mean poor general uptake of substances into mitochondria, there would not be a global problem.

Transport of substances into mitochondria is driven by specific transporters - different ones for different substances.

Their are some rare diseases associated with problems with particular transporters - here and here are reviews.

These transporters carry small molecules.

As well there is the transport of proteins encoded by nuclear genes but which function in the mitochondrion. Here is a review of that process. I don't know if there are known diseases associated with these transporters.
 
Thank you, @alicec!!!

alicec said:
If you mean poor general uptake of substances into mitochondria, there would not be a global problem.
Click to expand...
I think something like this is meant.
 
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I tested cysthationine and xanturic acid in a 24h urine test (cysthatinione without methionine load test, xanturic acid with tryptophan load test, which I won't repeat because I felt terrible). Another indicator is for me the "intolerance" to B6 intake and low ALP.
 
Inara said:
I tested cysthationine and xanturic acid in a 24h urine test (cysthatinione without methionine load test, xanturic acid with tryptophan load test, which I won't repeat because I felt terrible). Another indicator is for me the "intolerance" to B6 intake and low ALP.
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Hi there, sorry for bumping the thread but i too have had problems with vitamin d, pth, magnesium and alp. My doctor suspects adult hypophosphatasia because of my alp level that is in the 20s. I wonder how did you get hypophosphatasia ruled out and did you find any relief from anything and were you able to correct your low alp?
 
Hi @battle1, I went to a specialist for hypophosphatasia. I was told I don't have the known mutations. But I know that they're still doing research, so there should be found new mutations.

I do have a missense mutation in the ALPL gene, but it's probably not important. There are also other reasons for low ALP, and I'm still looking into this.

My ALP was somewhere around 29, but now it's relatively stable at 34. That's still low.

No, sadly I didn't find help with this problem. I asked around...but maybe I need to find a biochemist ALP researcher. I won't give up. :)
 
Inara said:
Hi @battle1, I went to a specialist for hypophosphatasia. I was told I don't have the known mutations. But I know that they're still doing research, so there should be found new mutations.

I do have a missense mutation in the ALPL gene, but it's probably not important. There are also other reasons for low ALP, and I'm still looking into this.

My ALP was somewhere around 29, but now it's relatively stable at 34. That's still low.

No, sadly I didn't find help with this problem. I asked around...but maybe I need to find a biochemist ALP researcher. I won't give up. :)
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Thanks for your reply. What are your symptoms and it seems hypophosphatasia wasn't ruled out after all. Did they look at your plp levels? Thanks :)
 
Yes, they also checked several lab results from the blood. I also had to do some urine tests, but they didn't look at them. I will have another look at the report. (They didn't look at B6 levels, i.e. PLP or P5P or...)

I have so many symptoms. (Please PM me if you want to know more.) I have ME symptoms, amongst others.
My symptoms don't seem to be typical for HPP, not even for grown-ups where HPP presents differently it seems, but I know of another person that was diagnozed with HPP and that has ME symptoms (especially PEM, too).
 
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