Polyneuropathy from small amounts of vitamins, b6 b1 b3 ...: loss of feeling in feet, pain, tingling

[dannybex]

• Endogenous oxalate production occurs in the glyoxylate pathway = glycation = diabetes (or "pre-diabetes")
• B6 is key for insulin sensitivity. However, gluconeogenesis also creates endogenous oxalates, so I believe there is a sweet point for carb intake...
• Glycation destroys hemoglobin = anemia
• B6 (and other Bs of course) are key in RBC/WBC synthesis

I agree re the glycation issues, but it's my understanding that the glyoxalate cycle/pathway exists only in plants and fungi (and bacteria?), not in the human body. I think.

Here -- @alicec writes about it on this page:

http://forums.phoenixrising.me/index.php?threads/oxalate-dumping-a-probiotic-solution.37927/page-19

 

[alicec]

it's my understanding that the glyoxalate cycle/pathway exists only in plants and fungi

The enzymes specific to the pathway do exist in humans and it probably does operate, at least under some circumstances. There's not much known about the human situation but in any case, the pathway doesn't seem to occupy the important position it does in plants.

Regarding endogenous oxalate production, I think the problem lies in terminology. Glyoxylate is the key intermediate which leads to oxalate accumulation. The B6 dependant enzyme AGxT (alanine glyoxylate aminotransferase) is the source of the problem - normally, it converts glyoxylate to harmless glycine but when it is not functioning well, glyoxylate accumulates and in turn can be converted to oxalate.

This reaction is NOT the glyoxylate cycle. That term specifically refers to the truncated Kreb's cycle I mentioned in the other post.

I think @Gondwanaland meant the AGxT reaction when she used the term glyoxylate pathway..

 

[Violeta]

Is there a possibility that lack of aldehyde dehydrogenase could be causing build up of B6 metabolites, (aldehyde), and that could be causing neuropathy?

"Catabolism of pyridoxal 5′phosphate involves the action of a phosphatase producing pyridoxal and then an aldehyde oxidase or aldehyde dehydrogenase producing 4-pyridoxic acid which is excreted in the urine. A number of phosphatases are active on PLP. These include pyridoxal phosphatase, the alkaline phosphatases, acid phosphatases and the PHOSPHO2 gene product. The relative importance of these different phosphatases in PLP homeostasis in different tissues is not known."


http://ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62646411

I am wondering if acetaldehyde is somehow involved with all three of the vitamins causing neuropathy, but I can't see how that would be. But here's an interesting link.

http://www.intelegen.com/nutrients/prevent_the_damaging_effects_of_.htm

Aldehyde dehydrogenase is certainly effective for nociception.

http://stm.sciencemag.org/content/6/251/251ra118

 

[Violeta]

From Susan Owens: "Brenda, the database scientists use to study enzymes does not seem to have any mammals with either glyoxylate cycle enzyme. Perhaps the debate is over."

 

[alicec]

From Susan Owens: "Brenda, the database scientists use to study enzymes does not seem to have any mammals with either glyoxylate cycle enzyme. Perhaps the debate is over."

My information about the existence of the glyoxylate cycle in humans is from Susan Owens. See the attached file.

 

[Violeta]

My information about the existence of the glyoxylate cycle in humans is from Susan Owens. See the attached file.

That statement is perhaps a more recent statement definitely from Susan Owens from her facebook group.

 

[Violeta]

This doctor says people w/b6 intolerance need more lysine. Not sure of the theory or reasoning behind it, but it's interesting that several companies sell lysine with b6.

Anyway, here's the link, the mention of B6 is in the comment section:

http://www.beyondmthfr.com/side-high-oxalates-problems-sulfate-b6-gut-methylation/

I was reading a post by Rydra a couple of days ago and she mentions that carnitine is the glucose gate for neuron; when deficient, too much glucose enters neurons and causes neuropathy (in some cases).

With respect to lysine possibly being related to neuropathy, someone sent me this link this morning that shows lysine being needed for carnitine production. I can see a few other things that might interfere if not available....ascorbic acid, Fe, and also betaine aldehyde dehydrogenase.

https://books.google.com/books?id=6cjgo1IixvEC&pg=PA494&lpg=PA494&dq=why is lysine needed for p5p&source=bl&ots=zmFnNw6t59&sig=5lhJNd-IS0s28lPwkHtiL3IQRRA&hl=en&sa=X&ved=0ahUKEwiCgtDD_dbKAhXCHT4KHZHrB1AQ6AEISDAH#v=onepage&q=why is lysine needed for p5p&f=false

 

[Lolinda]

Is there a possibility that lack of aldehyde dehydrogenase could be causing build up of B6 metabolites, (aldehyde), and that could be causing neuropathy?

This makes a lot of sense. - At least I can confirm that I probably do have a lack (or overburdening) of aldehyde dehydrogenase as I do not tolerate alcohol. None. Even ridiculously small amounts make me sick. I cannot think of anything else than not enough aldehyde dehydrogenase. And there is a second hint: I tried to trick out my B6 neurotoxicity by avoiding any peaks of B6, that is, by taking very small amounts and distributing them over the day. This was pretty good, I had no bigger worsening. -> It could make sense to assume that this scheme succeeded because it avoids B6 catabolism.

Do you have these too? @Violeta ? anyone else?
1. zero alcohol tolerance
2. no or almost no B6 neurotox when distributing small doses over the day (in me: 2/3 mg B6 divided into 3 doses per day -> I cannot judge any more if there is any slight increase of polyneuropathy symptoms)

Now, to find out if this has merit as a source of our B6 toxicity, a possible path could be to find out if the ordinary B6 toxicity reported in the literature (>500mg B6 per day) is because of aldehyde dehydrogenase overburdening. It would make sense to say that if this enzyme is already totally overburdened, then B6 toxicity can occur in very small doses. While I found lots of papers on B6 toxicity, I was unable to find a mechanism...

Another path could be to improve aldehyde dehydrogenase... I want to try this soon

 

[Lolinda]

It's quite common. Here's a link where hundreds reported problems with even tiny doses (as we've experienced):

http://www.medhelp.org/posts/Nutrition/B6-Toxicity/show/2642?page=1

Thanks once more for posting this link @dannybex I finally came to read these posts. well not all the 1100 but the first I dont know how many... One thing I recognize is that we are talking here on this PR thread about much smaller doses for much shorter time. On the medhelp forum, that is the classical published B6 toxicity: take B6 for 2 years or so in pharmacological doses and then you can get polyneuropathy. Some of their posts are somewhat under the published values: the smalles published values I know of are 100mg B6, and some users on medhelp report for example 50mg. But it is in the same ballpark. Now, I get it already from 4mg and I feel it already on the same day. If I remember it right, @Gondwanaland took B6 for some 10 days or so (?) also in really small doses. I dont know about the dosages of all others here. But it occurs to me that this issue in us is sthg very different from the "normal" B6 toxicigy. It cannot be the same mechanism...

@dannybex As you pointed me to the medhelp link, do you know by chance there reports on small doses or shortterm supplementation with B6 leading to polyneuropathy? I do not want to make you lose time into this, just in case you already know the answer or can get it with acceptable effort. Unfortunately they forgot the search option for "B6 intake <30mg/day"

 

[Gondwanaland]

Now, I get it already from 4mg and I feel it already on the same day. If I remember it right, @Gondwanaland took B6 for some 10 days or so (?) also in really small doses. I dont know about the dosages of all others. But it occurs to me that this issue in us is sthg very different from the "normal" B6 toxicigy. It cannot be the same mechanism...

Don't forget that when taken in higher doses many supps will have an inhibitory effect by negative feedback. When I took 30mg of B6 daily in my B complex my deficiency symptoms would only get exacerbated - lower thyroid, lower GABA etc. So I suppose that taking 4 mg is much more effective than taking 100 mg.

 

[Lolinda]

I see your logic. But there will also be effects increasing when increasing the intake. otherwise doctors would not treat people with for example inborn errors of B6 metabolism successfully with 100mg B6 per day.

 

[PennyIA]

I see your logic. But there will also be effects increasing when increasing the intake. otherwise doctors would not treat people with for example inborn errors of B6 metabolism successfully with 100mg B6 per day.

It could be based on the fact that SOME 'errors' are a factor type of error - so if you only get 10% or 20% of the B6 metabolized... then increasing the dosage to 100 mg, means you are getting 10 or 20 mg... which may be what you need.

For me, I had high homocysteine levels, and was treated with B6, B12, and Folic acid without testing my B vitamin levels first... and I got very, very ill with Folic Acid and cyanocobalamin and the standard form of B6 (can't remember it's type - not the P5P). B6 toxicity runs in my family with low doses of b6... I can't even take the b multi's because I don't tolerate any b6.

 

[Lolinda]

low doses of b6

I am curious: how much did you take and for how long? And did the neuropathy go away after you stopped? how long did it take, if so?

btw I tried your idea: took zinc for a few days. unfortunately no change. but it is not conclusive as at that time I reduced B6 intake to such low values that I was quite fine on it. (Finally, I dropped it completely. though I have a huge lot of benefits from B6, this polyneuropathy scares me much. over the weeks I had deteriorations while on very small dose of B6: 2/3mg distributed over the day, transdermally)

Btw @PennyIA , I am fairly sure I do have a genetic error of B6 metabolism. Though it does not run in our family, I do have several indications that I always had what is called B6 dependency, that is, need more B6 than normal and have clearly noticeable benefits if I do so and measurable issues if not. For example, I always had lowish rbc all my life that reacted to nothing on earth. but now I found out that they beautifully improve on B6. Interestingly, I had B6 levels at the top of the normal range already w/o supplements. Even more interestingly, I tolerated huge amounts of p5p, but that was quite some years ago, have to retest if it works now.
I initiated contact with researchers investigating inborn errors of B6. I hope I will be eligible for their estimated attention but it will be difficult to convince them as I have no epilepsy... do you?

high homocysteine levels,

if it still should be an issue, you may want to try glycine. lowers homocysteine and has many great effects. I can give details, references, experiences if that should be of interest.

 

[Gondwanaland]

if it still should be an issue, you may want to try glycine. lowers homocysteine and has many great effects. I can give details, references, experiences if that should be of interest.

Please do talk more about it

 

[PennyIA]

I am curious: how much did you take and for how long? And did the neuropathy go away after you stopped? how long did it take, if so?
...
I initiated contact with researchers investigating inborn errors of B6. I hope I will be eligible for their estimated attention but it will be difficult to convince them as I have no epilepsy... do you?

.. (reference to high homocysteine levels)

if it still should be an issue, you may want to try glycine. lowers homocysteine and has many great effects. I can give details, references, experiences if that should be of interest.

I was taking 50 mg 5 times a week. I never even though to try lower. It took about four months for me to get really ill, and within a year I was bed-ridden. Took three years to figure out that I thought it was B6 toxicity which my mother had also gotten diagnosed with, but two more years before I could convince anyone to give me the blood test. I only got the blood test in the end out of a out-and-out dare to the doctors. I told them that until they could run the test and prove that it wasn't b6 toxicity I wasn't going to do what they were asking me to do because they needed to prove it to me. And it was... and they just didn't know what to do about it and shrugged their shoulders over it. But at least I got the test and got proof that it wasn't doing me any good.

The neuropathy did NOT CHANGE even a little bit for several years afterwards. It wasn't until I started taking methylfolate and epsom salt baths to treat MTHFR defects that I saw any improvement - and it was pretty immediate improvement. About a month and I saw improvement right away and it hasn't ever been as bad since. I do sense more tingling and numbness when I take even 5 mg of B6 or P5P for two weeks .. and I get sick to my stomach smelling the supplement... so I've learned to stop taking it when it starts to smell bad. It's not gone bad. Same pill bottle smells fine a month later... so ... it's something that's triggering a reaction in me to the smell.

I don't have epilepsy nor alcohol intolerance... but I either have ME/CFS or a connective tissue disorder that I can't get diagnosed.

My homocysteine level lowered with b6, b12 and folic acid - funny enough. Even though I didn't tolerate them well, they lowered my homocysteine levels right away. I have a lot of family that is b12 deficient (which I now believe is related to MTHFR)... only because my mother couldn't remember the word for high homocysteine which she wanted to test herself for after my diagnosis due to clotting risk (I had a pulmonary embolism which is why mine was tested). She could remember it was related to b vitamin deficiencies, so that's what she tested herself for. Once she tested positive about 20% of my large extended family ALSO got tested and now are under treatment. Since they tested for B12 deficiency and NOT homocysteine levels, their treatment was b12 shots instead of the b6, folic acid and b12 tablets. They've had better luck on the shots than I had with the supplements I took. They never bothered to test my b vitamin levels until I'd been on them for a while.

 

[Gondwanaland]

high homocysteine which she wanted to test herself for after my diagnosis due to clotting risk (I had a pulmonary embolism which is why mine was tested)

I had endothelial damage followed by thrombosis and no one ever tested or mentioned homocysteine. The enocrinologist and the hematologist were just puzzled about my thrombosis The vascular dr was never curious about the causes, he prescribed me warfarin and wanted to remove a pair of my ribs It was only 2.5 years later when I saw an integrative dr that he requested this test. Then he prescribed me 300mg daily of B6 I left to never return

After this, I took B complexes with 30 - 60 mg of B6 (not P5P), which only worsened B6 deficiency symptoms. Magnesium helped a lot for 4 weeks only. Presently magnesium at any amount starting at 50mg triggers a huge urine volume and symptoms of low iron.

It was only a few weeks ago that some circumstances made me take P5P on its own (at six milligrams daily), and it was fantastic for 10 days, resolved all my problems with food intolerances and low thyroid. Then I had serotonin syndrome, followed a few days later by hypothyroidism

Back then I lowered homocysteine with diet (coconut oil) even though my B12 was very low, so insulin resistance is clearly involved. However, coconut oil "grabs" the B6 and makes it work on insulin receptors only, leaving me with very low lymphocytes and intolerant to oxalates.

Sorry if I repeat myself

 

[Lolinda]

ME/CFS or a connective tissue disorder that I can't get diagnosed.

I found that for connective tissue disorders one has to see a researcher. After exhausting a couple of rheumatologists, I headed to pubmed and fou d the foremost researcher of the country. She immediately ordered a full genetic test for all mutations that are known at present, even if my symptoms scores were under the limit both for Marfan and for EDS. You need a genetic test because the illness is as of tlday to some 95% or so defined by mutations. I can send you a copy of mine so you see what to look for. symptoms are not so useful here as symptoms have high variability even with people who have the same genes. everything else is a waste of time. fortunately, the sumptuous costs corresponding to ~5000 US bucks were paid by insurance. the trick is that if you have a researcher, the researcher is very motivated to collect data, hence she fought down with utmost professionalism all resistance by the insurance until they were forced to give in.

and as for cfs/me: why dont you just take the published consensus criteria available online? doctors dont do anything else.

 

[Lolinda]

glycine -> reduce homocysteine

Please do talk more about it

this link says it all, with references. I hope the references hold what they promise, I did not check all of them, the text was so professional that I trusted.
https://authoritynutrition.com/methionine-vs-glycine/
the fastest way to find the interesting spots is to search on the webpage for the word "reduce". there you get it all.

you will know these @Gondwanaland but for anyne else, here an easy to read page about all the general goodies from gelatine / glycine:
http://chriskresser.com/5-reasons-why-even-vegetarians-need-gelatin/

and my personal experiences with glycine: as I do not tolerate any supplements orally and no gelatine either, I take the glycine transdermally. I take some.3g to .7g at a time, rub it onto a tigh with a tiny amount of water. I have proof that it works because I have a clear feeling of relaxation afterwards (it does not come immediately, be ready to wait, can take some hours.) glycine is an inhibitory neurotransmitter in the brain, thats why. and dontbtake it all the day, because it is antiinflammatory, so you may end up with a flu if you use antiinflammatory things constantäy. for me its perfect if I rub my arms or legs before every meal and not at night. after the meal the glycine effect will be there when the methionine from the meal comes. I am looking forward to get tested soon if it really had an effect on my hhomocysteine. I have 10-12 levels of homocysteine when eating 250-300g of meat and a perfectly normal 8 when eating 150-200. I want to be able to eat much meat because thats what I tolerate, no carbs.

my general experiences with transdermal nutrients are here:
http://forums.phoenixrising.me/inde...complex-and-minerals.25743/page-2#post-743764

 

[Lolinda]

only got the blood test in the end out of a out-and-out dare to the doctors. I told them that until they could run the test and prove that it wasn't b6 toxicity I

happy to hear you succeeded

is there a blood test for b6 toxicity? I would immediately go and test for that. I did have tests for polyneuropathy, but thats just sudoscan and various electrical stimulation tests with needles, which have to do with polyneuropathy and not with the cause...

 

[Lolinda]

The neuropathy did NOT CHANGE even a little bit for several years afterwards. It wasn't until I started taking methylfolate and epsom salt baths to treat MTHFR defects that I saw any improvement - and it was pretty immediate improvement. About a month and I saw improvement right away and it hasn't ever been as bad since.

Thanks! Thats exactly the type of information I am looking for. I try to collect everything that gives me ideas how to get rid of this polyneuropathy thing. I dont like it

one more thing: was/is your polyneuropathy axonal or myelin-related? (it must be one of these. the neurologist who tested your polyneuropathy must have specified it in the report, if not he should print it out and eat the paper. his medical diploma too . mine is axonal)