Introduction
Hello everyone. I found this website today and have been reading it for hours along with scientific articles regarding vitamin B6 (PLP/P5P etc) toxicity. My specific interest was whether PLP plasma concentrations were noted. I got enough information from the free publications to hypothesize that PLP (as opposed to the other B6 vitamers) is likely the mechanism for causing peripheral neuropathy. I then learned that I need to be concerned about my low B12 and that it appears, my hypothyroidism, my blood tests, and diet are all connected.

Why am I here?
I am here because I think I have signs of neuropathy that perhaps are getting worse (or maybe just seem that way now that I am hypervigilant about them). I remember having them for possibly a year or two. I am hoping someone here can assist me in deciding the best course of action. I suspect I may have a gene mutation that requires me to supplement with B6 and B12, (perhaps other B vitamins too) which would comprise the entirety of my treatment plan for my condition.

As a lay person without access to a knowledgeable or willing doctor, I am unsure about all this. As you all are aware, medicine/biochemistry is probably exceptionally complex. I am still searching for a doctor that won’t dismiss my blood tests as ‘nothing to worry about’.

Today was abysmal, having seen my doctor a couple of days ago, her reluctance to help, her ignorance, her use of a search engine in front of me to look up ideas to explain my B6 (well at least she tried I suppose), and her insistence that elevated B6 is nothing to worry about, finally sapped almost all the hope out of me. Yet, here I am, having crawled out of the abyss, with the tiny bit of hope I have left, writing to you guys.

Don’t worry, even if you can’t help, reading here has already helped me more than my doctors ever have. Watching the B12 documentary with Sally Pacholok was so illuminating. For the information I’ve learned from people coming here and sharing their stories and for those that have knowledge to share, I am grateful to you already, so there’s no pressure to help


My PN symptoms
My recollection of symptoms is suspect because I think this is an insidious problem that has been masked by medication and anxiety for maybe a few years. For about 12 months or so, I had pins and needles in my arms, which I thought were caused by sleeping on my arms awkwardly. Despite exercising regularly, eating a diet that is devoid of processed food, not drinking or smoking, and getting plenty of sleep, I thought I should not be getting any circulation problems.

I developed chilblains on my fingertips, although it is a cold house, I didn’t normally get those other than on my toes in very cold weather. I would often not notice how cold my toes and fingers were before it was too late. Over the last couple of months I started wearing gloves almost all day and I have been wearing thick socks for years to avoid chilblains. I often had hot and tingling hands, sometimes feet, at night.

I suspected my symptoms to be caused in part by the gloves and socks. I also attributed the pins and needles in my arms to fluoxetine because when I came off it, all the tingling, pins and needles sensations dissipated. Over the last week, I stopped wearing gloves and noticed my hands felt slightly tingly, hot, and they felt like someone is holding them and squeezing them gently between theirs. I read in another thread here someone describing it as 'altered sensation', which really matches my perception of it. I use a computer all day most days, so I think I can be prone to repetitive strain injuries but with exercise and regular breaks I don't think I get many symptoms of that other than the occasional mild ache.

Whether this is PN or not, I am almost convinced that it is the precursor to some neurological problem that has been brewing for some time and the fact that it is now increasingly noticeable, albeit slowly, means I must tackle it now! I imagine some people may think this is nothing to be alarmed about but it is my B6 and B12 blood tests below that alarm and stress me. Sure, my symptoms can be almost forgotten when I am focused or distracted but that won’t hide the fact that my B6 levels are elevated despite never having taken a B6 supplement for years; last time was a modest amount in a multivitamin roughly 3 years ago.

I am lucky to know a very nice dietician. I can’t reach her very often and see her even less often due to her long waiting list. I don’t care that she doesn’t know why my B6 is high, I just appreciate that she is a nice person that shows a generous amount of empathy and as a consequence wants to help me with this if she can. Without her, I would not have been able to convince the doctor to have my B6 tested, so I am grateful for that. I have other symptoms that I am not sure are relevant and I think can be explained adequately as side effects of my medication but the most problematic is lethargy (from trial and error though I would consider fluoxetine to be the primary cause).


My medical status
Age: The fun side of 40 (:P)
BMI: 23
Non-autoimmune (my presumption) hypothyroidism (asymptomatic): TSH: 3.718mUI/L on 2017 01 16 at 25μg levothyroxine (lab safety parameters: 0.38 to 5.33mUI/L); (antithyroglobulin: 320 UI/mL (equivocal), antithyroperoxydase: <33.4 UI/mL (negative)).
Elevated vitamin B6: Vitamin B6/PLP/P5P/Pyridoxal phosphate via HPLC: 172nmol/L on 2017 01 16; 143nmol/L on 2016 09 16 (lab safety parameters: 35 to 110nmol/L)
*LOW* vitamin B12: Vitamin B12 via Beckman chimiluminescence: 260 pg/mL on 2016 09 14 (lab safety parameters: 180 to 914)

Sufficient liver function: transaminases SGOT ASAT: 24 UI/L (lab safety parameter: <41); transaminases SGPT ALAT: 30 UI/L (lab safety parameter: <42) Gamma-glutamyl transferase: 14 UI/L (lab safety parameters: 8 to 61) all on 2015 08 05
Sufficient renal function: GFR using MDRD formula: 102 ml/min on 2015 03 18 (lab safety parameter: >60)

SSRI discontinuation syndrome (from fluoxetine/Prozac): The iatrogenic aftermath of discontinuing fluoxetine too suddenly has been the hardest thing I’ve ever dealt with. I am recovering thanks to the help at ** For those interested, I am in a stabilisation phase at the moment, having reinstated. I will taper later this year using the 10% method with long holds, using water titration and syringes. I am well on my way to full recovery from my original condition, (under the anxiety umbrella), thanks to Cognitive Behavioural Therapy (self-taught via excellent books).

Lifestyle, diet, supplements, and medication
I had a look at the foods I eat that contain vitamin B6: These foods are almost my entire diet (aside from lots of fruit and nuts). So far I have learned that aside from renal insufficiency, a few other medical conditions that I don’t have, supplementing with B6, which I don’t do, and a genetic mutation, which I may have (which I still need to learn more about), it isn’t possible to have a plasma concentration of PLP as high as mine.
I eat these almost daily (usually every two days at least): sardines, spinach, cabbage, cauliflower, banana, broccoli, carrots, 500g lentils
I eat these at least once a week: brussels sprouts, tuna, leeks, chili peppers, avocado, beetroot I eat these every two to four weeks: salmon, peppers, asparagus, green peas, onions, pineapple, green beans, celery, strawberries, watermelon, lettuce, figs I only drink water and consume ~2 litres per day.
I try to exercise daily but that has become difficult the last week or so due to feeling so down about all this.

I take these supplements daily:
400mg Calcium
200mg Magnesium
25μg Vitamin D3
22mg Zinc
100μg Selenium

I take these supplements one day per week:
20mg Iron
225μg Iodine
1000mg Vitamin C

Having read the B12 thread and looked at some links and resources here, I have added this to my daily consumption (starting today):
5x1000μg Methylcobalamin (sublingual)
Starting not long after my B12 blood test (or perhaps not long before, I cannot recall), I used to take 1x1000μg Methylcobalamin (sublingual) a week.

My medication is currently: 20mg fluoxetine daily, 25μg levothyroxine daily.

Questions
I’d love to hear from anyone who has had elevated B6/PLP/P5P plasma concentrations without taking supplements. If you managed to get the levels down, how did you manage? If your B12 was a problem, please let me know too. I have heard a number of hypotheses about elevated B6 that I cannot find much objective evidence for. I am open-minded but I think the crux of this problem lies either in B12, perhaps my medication or supplements, or a genetic condition. If anyone can shed a little light on this, I would be grateful eternally. If there is any more information you need from me to help me with this, I can try to get it; i.e. other blood tests that I didn't think of sharing.

Wishing you moments of laughter and happiness whenever you can get them,

Kittygiggles.

Welcome to NeuroTalk...

Here is a good overview of B6 metabolism:
Vitamin B6, The Under-Appreciated Vitamin - Weston A Price

The gist of your post suggests to me that it is possible your blood was mishandled and therefore resulted in lysed cells (burst). B6 is in red blood cells and when they burst they release B6 into the serum causing a false high reading. This also happens with potassium testing. These artificial readings are called factitious.

Either that or the lab you are using is not calibrating its B6 samples properly so the whole test may be "off".

You do need to take B12 properly to have it be absorbed.
That means on an empty stomach once a day.

I think you should get a zinc test (and also a zinc/copper ratio).
There are posters here who tested very low in copper. Low copper is also found in MS patients, for some reason, and they get copper testing by their MS doctors, for this reason. High serum zinc can cause PN symptoms, and this was discovered by evaluating people who were "eating" their false teeth adhesives (or using too much) Today in US zinc is no longer in those products for this reason.

People who are anxious types breathe differently than others and this leads to minor increases in acid in the blood. Learning to breathe more normally can help this and reduce tingling feelings in those patients. There are many meditation sites on the net that teach calming breathing, and they can be very helpful for overly anxious patients. Some doctors use low dose tryptophan for their patients coming off SSRI's. Discuss this with your doctor. You can search this topic also on Google.

Absolutely! I am sorry for that error. I did mean low, especially as I read from here that 400 is the new low, and elsewhere I learned that in Japan they can consider 500 to be the cut-off for a low plasma concentration. Is there any way I would be permitted to edit my post? If not, would a moderator be allowed to just change it from 'Elevated' to 'Low'?

In light of my blood test, would you recommend continuing to supplement B12? I take B12 on an empty stomach, along with my medication, and vitamin D. Prior to the daily B12 supplementation I used to wait about an hour before eating; should I extend that waiting period? I've no problem doing so.

I am searching for a new doctor as my current one is reluctant to issue blood tests or for some reason 'compromises' and allows one or two things but not others, which is aggravating. I discuss my decisions with my dietician, who in turn does consult with doctors she knows; I'm in the process of getting their details but communication with her is slow.

As for zinc, I am happy to add this to my test. I started taking selenium, zinc, and iodine as I was advised they were useful for thyroid disorders. Having looked at my diet I can see lentils contain a great deal of zinc, and at the volume I eat them, I think I will stop taking it. My symptoms seemed more noticeable since taking zinc (about a few months ago).

Thank you for the advice about anxiety and breathing. I practice appropriate breathing when I am anxious and it works wonders. Still, I can forget sometimes. In addition, I suspect fluoxetine to be a culprit in this but also, I know very well the physical changes that happen with me when I am anxious, including tingling. However, this suspected PN seems constant.

I am so grateful to you for responding. Looking back at my post I can see it was a wall of text and I thought that perhaps it would put people off. Thank you again.

Be extremely careful taking any minerals with out getting all of your levels tested. If you are consuming plenty of zinc and taking zinc supplements you can drive your copper down. Better to get copper and ceruloplasm, iron, and ferritin, mag, cal, zinc, and iodine checked before messing around.

@bluesfan

Thank you for your encouragement and story.
Zinc: I had no real reason to take this as my diet contains a lot; I just did it due to advice about hypothyroidism. I thought I was cautious about taking supplements having only taken them when I actually identified a reason (rather than taking them ‘just in case’). However, since being here and learning more from my blood tests, supplements can have serious consequences sometimes so I will only take them based on evidence (i.e. blood tests and research).
Selenium: I stopped taking that too actually, since stopping the zinc. There’s quite a bit in my diet!

@mrsD

Thank you again for your input. The first link was one I had read before and made me ponder the possibility of having a gene mutation. If I can get it tested I will as soon as possible.
The second link I had not found despite scouring scientific journals for it! I have some great scientific literature about vitamin B6 and they all draw a similar conclusion: it’s undocumented (i.e. impossible at the moment) to develop B6 toxicity from food alone, which is my only source of B6. Although my diet is rich in B6 I discount it as a cause unless I find evidence to the contrary, which I suspect may not happen for some time. As you said, research on B6 tends to focus on deficiency rather than the few cases of megavitaminosis.

@Healthgirl

Thank you for the note about bacteria. I’ve no digestion problems but it could be an avenue to investigate if over the next few months I don’t get to the bottom of this. I now agree completely about being cautious with supplements! As for getting blood tests for what you suggested: unlikely to happen anytime soon. My current doctor (as mentioned previously) is really stubborn about blood tests and quite hard to predict. I am in the process of finding an easier avenue to get them done.

My hypothesis for good blood testing is just to do a whole bunch in one go. Then do a follow up a few months later, then I guess, annually, dismissing the minerals/vitamins that are at good levels. The way I get them now just seems like a waste of money and done almost at random (not my choice!)

Update

What I’ve done and am doing: Stopped zinc and selenium supplementation. Increased methylcobalamin consumption to 5microg per day on an empty stomach.

What I feel: Symptoms are still there but they are not worse. If anything I feel better which could be noticing the symptoms less often, feeling less anxious about it all since getting help here (thank you all again by the way), or the changes above. I am acutely aware of the power of hypervigilance on the body, so I always try to note symptoms when I feel my best and without too much thought.

My plan: Keep taking methylcobalamin at 5microg per day for about 1 month, stopping 3 days prior to a blood test (if I can get one), then recommence at 1microg per day until the results come out – then go from there. Additionally, I will try to test all the substances recommended in this thread, including a genetic test but that is at my doctor’s discretion (whom I hope to replace soon!)

Questions
I seem to have no adverse effects from methylcobalamin but I have one complaint: the sugar. I consume no refined sugar (not even honey) and I don’t like having sublingual pills that are full of sugar hanging around my mouth every morning! Does anyone know a good methylcobalamin pill without sugar? Taste is irrelevant, I don’t care about foul tasting medication! I noted your hypothesis mrsD about the molecule being too large to be absorbed via the tissue under the tongue and I am inclined to agree. This morning I just dissolved the pills in water then drank it, followed by more water to hopefully wash as much of the sugar away as possible.

This place has helped me feel so much better already and I appreciate the interest and sharing of knowledge. Sorry if I am over the top about it but I am sincerely grateful!

There shouldn't be sugar in your methylB12. This one which was at one time the only available form in US 10 yrs ago and by online purchase, does not have sugar in it:

Jarrow Formulas : Methyl B-12

We use now a locally available generic form from Costco, which also does not have sugar. Since historically B12 was sublingual before research showed it to work orally (swallow) there at one time may
have had sugar in them. But today they use artificial sweeteners in the tablets in case people still want to use them under the tongue.
Xylitol and mannitol are examples of sugar substitutes, and you might find sucralose (Splenda) in some brands.

One thing that seems to be lacking in studies on B6 elevations, is the fact that inactive B6 (pyridoxine) has to be activated to P5P the active form in order to work in the tissues. B2 (riboflavin) is a cofactor in the enzyme called pyridoxal kinase that does this job.

There also are drugs that inhibit pyridoxal kinase binding:

The conclusion of this article lists them at the end:
http://scholarscompass.vcu.edu/cgi/v...07&context=etd

Caffeine! That would be an issue for many people I expect.
So elevated B6 in serum could point to inefficient conversion of pyridoxine to P5P. This is one reason that P5P is more common today as a supplement. In fact one RX company was planning a drug containing only P5P in it. And there is another called Metanx that has P5P with methylcobalamin and methylfolate in it which is also RX in the US.

This is super interesting to me because the last neurologist I saw tried telling me that I don't actually have neuropathy and that I'm just an anxious breather/hyperventilating. He said he could tell because I sighed a lot and my blood pressure was through the roof (which it only ever is when I go to appointments) - I said this would cause numbness in my feet, burning in my legs, and tingling all over? He couldn't answer that. I have an autoimmune disease (RA) and a positive ANA but my neuropathy doesn't respond to prednisone or any immunosuppressive medication, also doesn't respond to LDN. I haven't found ONE doctor that thinks my neuropathy is autoimmune mediated, where as I can't figure out how it isn't autoimmune mediated. But... you know, the fun of neuropathy is figuring out why it's happening, right? (that's sarcasm, of course)

One way you can test if your breathing is a culprit:

Do your symptoms come and go? That could suggest a breathing link (certain periods of hyperventilation or stress). It they are the same all or most of the time irregardless of activity or consuming an irritating food, or MSG, I'd think more of a RA trigger, or prediabetes, or a toxin, or virus.

This is where a daily journal could be helpful.

Some of the PN burning resembles the burning a person can get from coming into warmth after being in severe cold. Feet, hands, ears, etc, can burn when they warm up.

Just a couple of years or so ago, both my son and I got burning feet from a perch fish lunch on vacation. Within a couple of hours or less we both had to take our shoes and socks off! Less than fresh fish, harbor histamine producing bacteria. Histamine = burning and redness in some people.

I appreciate the interest in this thread. I'd just like to iterate, in case anyone missed it:

"In light of my blood test, would you recommend continuing to supplement B12? I take B12 on an empty stomach, along with my medication, and vitamin D. Prior to the daily B12 supplementation I used to wait about an hour before eating; should I extend that waiting period? I've no problem doing so."

Sadly, my tingling and burning symptoms, although tolerable, can be distracting and are constant. I've been keeping a daily diary of symptoms, supplements, and medication for years, as part of CBT but also to manage other health issues.

I hope that my suspected PN is due to fluoxetine, which will dissipate as I taper later this year but my high B6 and low B12 are red flags that perhaps I could have a mutated relevant gene, or some imbalance/toxicity. Additionally, would the laboratory make the same mistake twice with my B6? I have heard of such a thing before but assumed it was rare.

It's only been one day but there's no improvement yet since stopping zinc.

One other symptom that I thought could be relevant is my 'vibrating fingers', i.e. shaky hands but mostly my fingers. I've had that for probably 10 years or more. Because of its duration I dismissed it as irrelevant but I am wondering about it again.

Your B12 is LOW... below the 400pg new low threshold.

So yes, you should continue with it.

Quest diagnostics had two episodes of faulty measurement of Vit D. Each lasting a year! It was quite the scandal as many people received inaccurate test results. They said it was because of faulty erroneous calibration. You can Google this and read more.
Never trust a lab test 100%... as errors are common.

One thing you should do is get the DNA testing for MTHFR....many people have mutations in methylation, and it is considered fairly common today. But not all doctors are up on the science.
Using methylcobalamin is one treatment but if you have the mutation(s), you need methylfolate as well.

Here is good source for further information:
MTHFR Mutation | MTHFR Gene Mutation | What is MTHFR? - MTHFR.net

Getting tapered off the Prozac may help. That is a slow process, as Prozac has a long half life.