The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function

[helvella]

The taking of B-complexes, and of just B6, has often been disussed here. I, along with several others, have pointed out that high doses of B6 should be avoided as they can cause neuropathy - one of the symptoms that it is sometimes taken to help relieve.

This paper, from 2017 and hitherto completely missed by me, has an explanation for this phenomenon.

What it doesn't do is give information about doses. It appears to say that other forms of B6, such as pyridoxal-5'-phosphate, do not cause this issue.

Toxicol In Vitro. 2017 Oct;44:206-212. doi: 10.1016/j.tiv.2017.07.009. Epub 2017 Jul 14.

The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function.

Vrolijk MF1, Opperhuizen A2, Jansen EHJM3, Hageman GJ4, Bast A4, Haenen GRMM4.

Author information

1 Department of Pharmacology and Toxicology, Maastricht University, Maastricht, The Netherlands. Electronic address: [e-mail].

2 Department of Pharmacology and Toxicology, Maastricht University, Maastricht, The Netherlands; Netherlands Food and Consumer Product Safety Authority (NVWA), Utrecht, The Netherlands.

3 National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

4 Department of Pharmacology and Toxicology, Maastricht University, Maastricht, The Netherlands.

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.

Copyright © 2017 Elsevier Ltd. All rights reserved.

KEYWORDS:

Neuropathy; Neurotoxic; Pyridoxine; Supplements; Vitamin B6

PMID: 28716455

DOI: 10.1016/j.tiv.2017.07.009

ncbi.nlm.nih.gov/pubmed/287...

[Hidden]

So does that mean you need to take a B complex that doesn't contain Pyridoxine? Are any available?

[helvella Administrator Thyroid UK in reply to Hidden]

I'd be surprised if there weren't any. But I have not checked and have no information myself.

[Hidden in reply to helvella]

I have never noticed if B complexes specify the kind of B6, unlike vitamin Ds

[helvella Administrator Thyroid UK in reply to Hidden]

At least some multivitamins do!

For example, and this was selected more-or-less randomly:

BioCare Adult Multivitamins & Minerals

Vitamin B6 (As Pyridoxal-5-Phosphate)

smile.amazon.co.uk/Biocare-...

And some B-complexes:

Thorne Research - Basic B Complex - B Vitamins in Their Active Forms - 60 Capsules

Vitamin B6 (15 mg of pyridoxal-5'-Phosphate)

smile.amazon.co.uk/Thorne-R...

[SeasideSusie Remembering in reply to Hidden]

So does that mean you need to take a B complex that doesn't contain Pyridoxine? Are any available?

I have read that it is recommended that a safe level to supplement is no more than 10mcg daily, there are B Complex supplements that have this amount. I personally would avoid any with a higher amount.

If you do look for and find one without B6, check what the doses of the other B vitamins it contains are.

[Hidden in reply to SeasideSusie]

Thanks. Do you know what is the ideal mixture/balance there should be in a complex? I did look up a couple of recommended brands but they were expensive so I bought a cheaper one in the end

[SeasideSusie Remembering in reply to Hidden]

No, I don't know what the ideal balance is, but unless we test each B vitamin individually then we wont know exactly what we need. But certainly avoid the supplements that have the same amount of everything, eg B50s and B100s.

Personally I found that Thorne Basic B suited me when I had a very low folate level. It has 400mcg of both methylfolate and methylcobalamin. Now, because my B12 is very good with an Active B12 test then I don't need 400mcg methylcobalamin so I have changed to a food based B Complex with a different balance, it has only 24mcg methylcobalamin but still has 400mcg methylfolate and is keeping my folate at a good level. This one contains just 5mg B6.

If your B Complex contains folic acid and cyanocobalamin, be aware that these are the cheaper alternatives to methylfolate and methylcobalamin, and are versions that are not generally recommended.

[janey1234]

It's early, I'm confused 🥴....I take Igennus B Complex, which is often recommended here, which contains 20mg of Vitamin B6 (As Pyridoxal-5-Phosphate). Is that too high?

[helvella Administrator Thyroid UK in reply to janey1234]

Pyridoxal-5-Phosphate was not identified as a problem in that study. Only pyridoxine is an issue.

I have no idea whether that is an appropriate dose of Pyridoxal-5-Phosphate.

[janey1234 in reply to helvella]

thank you 🙂

[wellness1]

Thanks for this. Another aspect of 'optimum' levels of B6...

I recently happened on a reference to B6 on the BetterBones site.

"VITAMIN B6 is one of the B vitamins that has been linked to fracture healing. Animals deficient in this vitamin fracture more frequently and experience reduced fracture healing. It appears that vitamin B6 modulates the effects of vitamin K on bone through complex biochemical pathways." (no citation given)

However, I came upon a study that argues against *over*supplementation of B6 and B12.

"We found that high intakes of vitamins B6 and B12 were associated with increased hip fracture risk among postmenopausal women in the Nurses’ Health Study. The risk was highest in women with a combined high intake of both vitamins, exhibiting an almost 50% increased risk of hip fracture compared with women with a low intake of both vitamins."

jamanetwork.com/journals/ja...

[helvella Administrator Thyroid UK in reply to wellness1]

That paper refers to the research I posted!

A recent paradox theory proposes that large doses of pyridoxine, the inactive form of vitamin B6 included in supplements and found in foods, inhibits the active form pyridoxal phosphate.

But what the paper doesn't do is identify which form of B6 (which vitamer) was being supplemented. From reading product details, an awful lot use pyridoxine - the problem vitamer.

[wellness1 in reply to helvella]

Yes, at least they acknowledge the limitations of the study.

The lack of specificity in both the research and commercial contexts is frustrating.

[Luna1390]

Hi there! This actually happened to me, so thought I would share my experience. I started taking 50 mg pyridoxine and within a few weeks, I developed tingling and numbness in my hands & feet. I also had heart symptoms (felt like my heart was shaking in my chest). I stopped all pyridoxine. I even had to eliminate B6-containing foods for several months. It took about 6 months to get better. I was lucky because I had just read B6 could cause nerve issues, so when it started, I knew to stop immediately. Dr. Alan Christianson says it is due to a person's body not being able to convert pyridoxine into active B6, so the pyridoxine just builds up instead. I also cannot tolerate P5P, so I make sure I eat B6 foods and that keeps my levels optimal.

[Luna1390 in reply to Luna1390]

P5P causes me to have anxiety and insomnia, not nerve issues. Just to clarify.

[humanbean]

About 10 years ago I took a B Complex with a large amount of pyridoxine in. I think I probably was deficient or low to begin with and I did have some neuropathy issues in my feet at the time. Over a period of a couple of months or so of supplementing my neuropathy did diminish.

Then I jogged along okay for a few weeks while I still took it then I started having problems with my feet again. Luckily I did my research and quite quickly found out it was a toxicity problem with vitamin B6 and I stopped taking any kind of B Complex for a few years. My feet did improve once I stopped the B Complex but they took longer to recover completely than when I was deficient.

When I started taking a B Complex again as a result of things I read on thyroid forums I only bought B Complex with fairly low doses and all activated vitamins. I haven't had neuropathy problems since.

[QUE6T-33 in reply to humanbean]

Hi Humanbean, just read this link, which B complex did you find worked for you please ? Perhaps you could p.m. me. Thank you.

[humanbean in reply to QUE6T-33]

I've been happy with both the Thorne Basic B Complex :

thorne.com/products/dp/basi...

and Igennus Super B Complex :

igennus.com/products/super-...

I'm using the Igennus product now because a) it is cheaper than the Thorne product and b) I find it hard to believe I am still deficient in any of the B vitamins. (I've only ever tested folate and B12.) The Igennus dose is one tablet twice a day. I only take one per day. I do still struggle for some reason to keep my folate level up, so I supplement with a separate methylfolate supplement every other day, as well as the Igennus.

[QUE6T-33 in reply to humanbean]

Thanks Humanbean, yep Folate & B12 are tricky little ...... 😊. Appreciate the info.

[helvella Administrator Thyroid UK in reply to QUE6T-33]

I know humanbean has now responded, but it is much better for information like this to be in the open than tucked away in Private Messages.

If anyone had more information, about the products, maybe prices, or good alternatives, it is easy for them to add responses when it is all in public. They might not have any idea it would be useful if they can't even see the information!

[humanbean in reply to helvella]

Another issue is that when people post in public other people can highlight any mistakes! That can't happen with PMs.

[QUE6T-33]

Totally agree Helvetia, just never sure what’s permissible & not, so like to offer the option to responder to pm if wish to.