This is the
talk page for discussing improvements to the
Megavitamin-B6 syndrome article. This is not a forum for general discussion of the article's subject. |
Article policies
|
Find medical sources: Source guidelines · PubMed · Cochrane · DOAJ · Gale · OpenMD · ScienceDirect · Springer · Trip · Wiley · TWL |
![]() | This article is rated C-class on Wikipedia's
content assessment scale. It is of interest to the following WikiProjects: | ||||||||||||||||
|
![]() | Ideal sources for Wikipedia's health content are defined in the guideline
Wikipedia:Identifying reliable sources (medicine) and are typically
review articles. Here are links to possibly useful sources of information about Megavitamin-B6 syndrome.
|
![]() |
Daily pageviews of this article
A graph should have been displayed here but
graphs are temporarily disabled. Until they are enabled again, visit the interactive graph at
pageviews.wmcloud.org |
![]() |
|
I originally started this in
User:Scarpy/Vitamin B6 Toxicity, but migrated to
User:Scarpy/Megavitamin-B6 syndrome when I realized that was the most official name. There is a large list of unused sources and various reasons for why in
User talk:Scarpy/Vitamin B6 Toxicity. In the past I have typically written articles in my sandbox, then copied and pasted in to the main space, but have since read that it's a better practice to move them. So that's what I'm doing here. -
Scarpy (
talk)
01:39, 10 December 2019 (UTC)
Scarpy, do you think the intro has a WP:ISATERMFOR problem? Kolya Butternut ( talk) 20:57, 7 February 2020 (UTC)
Megavitamin-B6 syndrome is a collection of symptoms that can result from chronic supplementation, or acute overdose, of vitamin B6. In addition to the ICD-10 name, it is also known as hypervitaminosis B6, vitamin B6 toxicity and vitamin B6 excess.Kolya Butternut ( talk) 01:02, 11 February 2020 (UTC)
@ SchreiberBike: of course I see your point here. I've seen people with Megavitamin-B6 syndrome commenting on this article outside of Wikipedia (on Facebook) and their primary complaint is that it takes many people more than six months to recover. They're reading the same text that you and I are, but taking away a different meaning from it. Hence the reasoning for change in the wording. - Scarpy ( talk) 23:19, 10 February 2020 (UTC)
A single purpose account (see
WP:SPA)
removed the bit from Gangsass 1995 about the lack of evidence showing b6 is effective at treating premenstrual syndrome. But just that bit and not the rest of the material supported by that source ...have not found it to be effective at reducing swelling, reducing stress, producing energy, preventing neurotoxicity, or treating
asthma
.
1995 was a long time ago, but I was keeping WP:MEDDATE here as there aren't more recent reviews on what B6 is not effective at treating (if someone finds one, feel free to correct me). Taking a look at the material published since 1995.
My take away is that good, more recent, sources here are those reporting on the Waytt 1999 review. e.g. [1] (2003) [2] (2009) [3] (2003)
I think our SPA is correct that there was Level B evidence 4 years after Gangsass was published for vitamin b6 treating premenstrual syndrome. We should emphasize that it's not Level A, and take pains to mention it's not dose dependent and that the sources cite the possibility of neuropathy with high doses.
Thoughts? - Scarpy ( talk) 17:50, 23 September 2020 (UTC)
I want to talk a bit about these edits. These are for sure good faith edits, and information I considered including in this article previously. I want to address a few of these.
First point, including pyridoxine toxicity, pyridoxine poisoning, and pyridoxine neuropathy in the lead -- there's a lot of synonyms for megavitamin-b6 syndrome. Putting all these in the leads is low-value so they appear in the foot notes.
Second - I can't find a single reliable source that makes a distinction between "synthetic" and "non-synthetic" vitamin b6. There are plenty of articles that say there's no documented cases of toxicity from food. I also can't find anything that says there's a difference between "food-sourced" and "synthetic" forms of b6. It's not in Vrolijk 2017 in any case.
Third - Vrolijk 2017 is a great article, but it's an in vitro study, and contradicts other in vivo studies that shows toxicity from other b6 vitamers. These are already mentioned in the article.
Fourth - the rule of thumb for writing WP:MEDRS articles is "cite reviews, don't write reviews." I followed that the best I could here other than in cases where the was something that was very important that was not yet included in a review. In the case of Vrolijk 2017, it was always mentioned in a review, so I cited the review rather than the article. This is just Wikipedia practice.
Fifth - I double checked Dalton and Dalton 1987, and I don't see anything that supports the statement Subtle neurological symptoms can already be observed at daily intakes of 1 to 10 mg/kg
. This looks like
WP:OR to me. Dalton and Dalton 1987 also falls under the same guidance of "cite reviews, don't write reviews." It's also kind of silly guidance -- someone that's 150lbs would be 68kg. So 1mg to kg would be 68mg, which is above all the established TULs (except for the US). 10mg per kg would be 680mg for that 150lbs person, which is crazy, crazy, crazy, high.
So I hope you won't take it personally, but I'm going to revert these changes. I'm happy to discuss them further, however. - Scarpy ( talk) 07:46, 13 January 2021 (UTC)
I think either Vrolijk or another reference cited Dalton and Dalton in such words.I re-read both and I don't see anything matching that claim. Are you able to cite the text from the article that you're using to support this?
I would genuinely be very interested in sources about toxicity of pyridoxal.A good place to start with be the sources in the existing version of the article. In addition to Vrolijk 2017 there are three other articles cited supporting the sentence that states: "Symptoms also appear to be dependent on the form of vitamin B6 taken in supplements. It has been proposed that vitamin B6 in supplements should be in pyridoxal or pyridoxal phosphate form rather than pyridoxine as these are thought to reduce the likelihood of toxicity." I went that far because the 2019 review did, but previous articles and work contradicts it. You can click on the superscript numbers in brackets to see these in the article, I've also reproduced them below quoting relevant parts.
The toxicity of vitamin B6 is not only dose determined, but related to the vitamer in which it is taken. There is a proposal that pyridoxine should be replaced by pyridoxal or pyridoxal phosphate when vitamin B6 supplements are requirednote they're saying "a proposal" they're not saying with certainty that pyridoxine is the only toxic form or than pyridoxal phosphate would not cause toxicity.
Vitamin B6, which includes pyridoxine, pyridoxal, and pyridoxamine upon phosphorylation, functions and an essential cofactor of many imporant enzymatic reactions, particularly those of amino acid metabolism. It occurs widely in foods and deficienty in man is rate, though pregnant women and those on oral contraceptives may be at particular risk of deficiency... The therapeutic use of pyridoxine has not been proven as effective exception in association with inborn errors of vitamin b6 metabolism, the presence of a vitamin B6 antagonist, or a true dietary deficiency of the vitamin... Pyridoxal is several times as toxic as other forms of the vitamin, though it's toxicity is still quite low.
...the vitamin has special interest because it is not known if its toxicity is related to one or more of its numerous physiological functions or to a still unknown metabolite of the original molecule or of the other vitamers to which it may be converted in vivo... Pyridoxine is interconvertible in vivo with the vitamers pyridoxal and pyridoxamine. In order to find the mechanism for the neurotoxicity of pyridoxine, it was important to determine if these vitamers caused similar clinical signs and histological lesions as the parent vitamin.... The vitamer pyridoxal and the coenzyme pyridoxal 5- phosphate were more toxic than pyridoxine. They did not produce clinical signs or lesions in ganglia similar to those produced by pyridoxine even though maximum tolerated doses were injected. The vitamer pyridoxamine was somewhat less toxic, which made it possible to study effects after doses that matched or exceeded the doses of pyridoxine. Nevertheless, the results were negative. Pretreatment with the sucrose diet as described above, or preparation with bilateral nephrectomy as described previously, did not elicit signs or lesions in trigeminal ganglia... It is not known if the neurotoxicity of large doses of pyridoxine is caused by the unaltered pyridoxine molecule, by the vitamers or the active coenzyme, by intermediates involved in the conversion to coenzyme or by some unknown derivative. This unsolved problem is important because of the continued, contemporary therapeutic use of large doses of pyridoxine.... Contributing to this last issue is a study by Windebank (1985), who found almost equal toxicity to cultures of dorsal root ganglia neurons from pyridoxine as from the other B6-vitamers (pyridoxal and pyridoxamine). This observation tended to link pyridoxine toxicity to its coenzyme function. In support of such a linkage, the three vitamers are known to be interconvertible through the activity of pyridoxine oxidase and pyridoxine kinase, yielding the active coenzyme pyridoxal 5-phosphate (McCormick and Chen, 1999). The importance of the present work is that we have demonstrated that the question of neurotoxicity by the B6- vitamers in vivo was not settled by the in vitro experiments, which found no differences among them (Windebank, 1985). Further study must include assays of each of the vitamers in serum and in the target neural tissues. The incentive for such a study is the possibility that the pyridoxine molecule itself, or a presently unsuspected metabolite, might be responsible for the neurotoxicity.
Question for the article is, how do toxic doses of pyridoxal compare to pyridoxine. I think the article is missing this clear distinction.
The article's bolded words are misleading because there is evidence that pyridoxine is much more toxic than pyridoxal.
However, some people are developing neuropathy precisely because of a long-term, accumulated multiple vitamin B deficiency.
To use the more general label "B6" is an attempt to scare people away from supplementation.
People should be less deterred from a high quality vitamin B complex (containing pyridoxal, a hydrogenated folate, cofactors etc.).
we really only have Levine “versus” Vrolijk here
several analogs of pyridoxine were neurotoxic in vitro. Those that may be converted into active coenzymes— pyridoxal, pyridoxine, and pyridoxamine— were almost equal in, toxicity. Pyridoxic acid, which is not active, was nontoxic. Pyridoxamine 5-phosphate, which cannot enter cells, also was nontoxic. Several hypotheses that link coenzyme function to toxic effect are described.Other than the cells being derived from rats, it's more relevant an experiment as we know that DRG are involved with the megavitamin-b6 syndrome, rather than cancer cells that have less causal and mechanistic relevance (even if they distally came from humans). I'm not sure what became of his work here, because he outlined several hypothesis and had some other things in press, but it doesn't look like there was much follow-up on his paper.
Dogs, rats, and rabbits were able to tolerate short-term doses of up to 1 gm/kg/day without ill effects (Unna, 1940; Unna and Antopol, 1940. Delorme and Lupien, 1976), but with higher doses or the long-term administration of as less as 200 mg/day, ataxia, muscle-weakness and progressive neurotoxicity occurred (Phillips et al. 1978). Pyridoxal is several times as toxic as the other forms of the vitamin, though its toxicity is still quite low. There is no evidence of teratogenicity (Khera, 1975) or carcinogenicity (Visek et al., 1978) from large doses of pyridoxine.
I'm looking more carefully at Nutritional Toxicology V1. While that book appears to have been published in 2012, Chapter 3 in that book, "Vitamin Excess and Toxicity" looks like it was published in 1982. Some evidence:
I believe given that it fails WP:MEDRS as it's too old and there's newer reviews. So I'm going to remove the content it supports. - Scarpy ( talk) 22:02, 17 January 2021 (UTC)
If anyone is interested, the editor for that text book, John N. Hathcock, passed away in 2019. I can't find affiliations for DR Miller or KC Hayes, so I'm not sure if we'll ever know if the bit about pyridoxal vs pyridoxine was a mistake there. Either way, still don't think it's MEDRS here. John N. Hathcock seemed like a brilliant man, though. - Scarpy ( talk) 07:53, 20 January 2021 (UTC)
@
David notMD:
Thanks for this. One small thing. The edit summary says Exceptions: deleted mention of suppressing lactation (1998 ref) as a recent systematic review (PMID 28425125) concluded clinical trial evidence inconclusive
. I think you meant
28425124 as
28425125 is way different. -
Scarpy (
talk)
09:25, 20 February 2021 (UTC)
Quick look identified a few weak or inappropriate refs. All should be looked at. David notMD ( talk) 03:07, 21 August 2021 (UTC)
This is the
talk page for discussing improvements to the
Megavitamin-B6 syndrome article. This is not a forum for general discussion of the article's subject. |
Article policies
|
Find medical sources: Source guidelines · PubMed · Cochrane · DOAJ · Gale · OpenMD · ScienceDirect · Springer · Trip · Wiley · TWL |
![]() | This article is rated C-class on Wikipedia's
content assessment scale. It is of interest to the following WikiProjects: | ||||||||||||||||
|
![]() | Ideal sources for Wikipedia's health content are defined in the guideline
Wikipedia:Identifying reliable sources (medicine) and are typically
review articles. Here are links to possibly useful sources of information about Megavitamin-B6 syndrome.
|
![]() |
Daily pageviews of this article
A graph should have been displayed here but
graphs are temporarily disabled. Until they are enabled again, visit the interactive graph at
pageviews.wmcloud.org |
![]() |
|
I originally started this in
User:Scarpy/Vitamin B6 Toxicity, but migrated to
User:Scarpy/Megavitamin-B6 syndrome when I realized that was the most official name. There is a large list of unused sources and various reasons for why in
User talk:Scarpy/Vitamin B6 Toxicity. In the past I have typically written articles in my sandbox, then copied and pasted in to the main space, but have since read that it's a better practice to move them. So that's what I'm doing here. -
Scarpy (
talk)
01:39, 10 December 2019 (UTC)
Scarpy, do you think the intro has a WP:ISATERMFOR problem? Kolya Butternut ( talk) 20:57, 7 February 2020 (UTC)
Megavitamin-B6 syndrome is a collection of symptoms that can result from chronic supplementation, or acute overdose, of vitamin B6. In addition to the ICD-10 name, it is also known as hypervitaminosis B6, vitamin B6 toxicity and vitamin B6 excess.Kolya Butternut ( talk) 01:02, 11 February 2020 (UTC)
@ SchreiberBike: of course I see your point here. I've seen people with Megavitamin-B6 syndrome commenting on this article outside of Wikipedia (on Facebook) and their primary complaint is that it takes many people more than six months to recover. They're reading the same text that you and I are, but taking away a different meaning from it. Hence the reasoning for change in the wording. - Scarpy ( talk) 23:19, 10 February 2020 (UTC)
A single purpose account (see
WP:SPA)
removed the bit from Gangsass 1995 about the lack of evidence showing b6 is effective at treating premenstrual syndrome. But just that bit and not the rest of the material supported by that source ...have not found it to be effective at reducing swelling, reducing stress, producing energy, preventing neurotoxicity, or treating
asthma
.
1995 was a long time ago, but I was keeping WP:MEDDATE here as there aren't more recent reviews on what B6 is not effective at treating (if someone finds one, feel free to correct me). Taking a look at the material published since 1995.
My take away is that good, more recent, sources here are those reporting on the Waytt 1999 review. e.g. [1] (2003) [2] (2009) [3] (2003)
I think our SPA is correct that there was Level B evidence 4 years after Gangsass was published for vitamin b6 treating premenstrual syndrome. We should emphasize that it's not Level A, and take pains to mention it's not dose dependent and that the sources cite the possibility of neuropathy with high doses.
Thoughts? - Scarpy ( talk) 17:50, 23 September 2020 (UTC)
I want to talk a bit about these edits. These are for sure good faith edits, and information I considered including in this article previously. I want to address a few of these.
First point, including pyridoxine toxicity, pyridoxine poisoning, and pyridoxine neuropathy in the lead -- there's a lot of synonyms for megavitamin-b6 syndrome. Putting all these in the leads is low-value so they appear in the foot notes.
Second - I can't find a single reliable source that makes a distinction between "synthetic" and "non-synthetic" vitamin b6. There are plenty of articles that say there's no documented cases of toxicity from food. I also can't find anything that says there's a difference between "food-sourced" and "synthetic" forms of b6. It's not in Vrolijk 2017 in any case.
Third - Vrolijk 2017 is a great article, but it's an in vitro study, and contradicts other in vivo studies that shows toxicity from other b6 vitamers. These are already mentioned in the article.
Fourth - the rule of thumb for writing WP:MEDRS articles is "cite reviews, don't write reviews." I followed that the best I could here other than in cases where the was something that was very important that was not yet included in a review. In the case of Vrolijk 2017, it was always mentioned in a review, so I cited the review rather than the article. This is just Wikipedia practice.
Fifth - I double checked Dalton and Dalton 1987, and I don't see anything that supports the statement Subtle neurological symptoms can already be observed at daily intakes of 1 to 10 mg/kg
. This looks like
WP:OR to me. Dalton and Dalton 1987 also falls under the same guidance of "cite reviews, don't write reviews." It's also kind of silly guidance -- someone that's 150lbs would be 68kg. So 1mg to kg would be 68mg, which is above all the established TULs (except for the US). 10mg per kg would be 680mg for that 150lbs person, which is crazy, crazy, crazy, high.
So I hope you won't take it personally, but I'm going to revert these changes. I'm happy to discuss them further, however. - Scarpy ( talk) 07:46, 13 January 2021 (UTC)
I think either Vrolijk or another reference cited Dalton and Dalton in such words.I re-read both and I don't see anything matching that claim. Are you able to cite the text from the article that you're using to support this?
I would genuinely be very interested in sources about toxicity of pyridoxal.A good place to start with be the sources in the existing version of the article. In addition to Vrolijk 2017 there are three other articles cited supporting the sentence that states: "Symptoms also appear to be dependent on the form of vitamin B6 taken in supplements. It has been proposed that vitamin B6 in supplements should be in pyridoxal or pyridoxal phosphate form rather than pyridoxine as these are thought to reduce the likelihood of toxicity." I went that far because the 2019 review did, but previous articles and work contradicts it. You can click on the superscript numbers in brackets to see these in the article, I've also reproduced them below quoting relevant parts.
The toxicity of vitamin B6 is not only dose determined, but related to the vitamer in which it is taken. There is a proposal that pyridoxine should be replaced by pyridoxal or pyridoxal phosphate when vitamin B6 supplements are requirednote they're saying "a proposal" they're not saying with certainty that pyridoxine is the only toxic form or than pyridoxal phosphate would not cause toxicity.
Vitamin B6, which includes pyridoxine, pyridoxal, and pyridoxamine upon phosphorylation, functions and an essential cofactor of many imporant enzymatic reactions, particularly those of amino acid metabolism. It occurs widely in foods and deficienty in man is rate, though pregnant women and those on oral contraceptives may be at particular risk of deficiency... The therapeutic use of pyridoxine has not been proven as effective exception in association with inborn errors of vitamin b6 metabolism, the presence of a vitamin B6 antagonist, or a true dietary deficiency of the vitamin... Pyridoxal is several times as toxic as other forms of the vitamin, though it's toxicity is still quite low.
...the vitamin has special interest because it is not known if its toxicity is related to one or more of its numerous physiological functions or to a still unknown metabolite of the original molecule or of the other vitamers to which it may be converted in vivo... Pyridoxine is interconvertible in vivo with the vitamers pyridoxal and pyridoxamine. In order to find the mechanism for the neurotoxicity of pyridoxine, it was important to determine if these vitamers caused similar clinical signs and histological lesions as the parent vitamin.... The vitamer pyridoxal and the coenzyme pyridoxal 5- phosphate were more toxic than pyridoxine. They did not produce clinical signs or lesions in ganglia similar to those produced by pyridoxine even though maximum tolerated doses were injected. The vitamer pyridoxamine was somewhat less toxic, which made it possible to study effects after doses that matched or exceeded the doses of pyridoxine. Nevertheless, the results were negative. Pretreatment with the sucrose diet as described above, or preparation with bilateral nephrectomy as described previously, did not elicit signs or lesions in trigeminal ganglia... It is not known if the neurotoxicity of large doses of pyridoxine is caused by the unaltered pyridoxine molecule, by the vitamers or the active coenzyme, by intermediates involved in the conversion to coenzyme or by some unknown derivative. This unsolved problem is important because of the continued, contemporary therapeutic use of large doses of pyridoxine.... Contributing to this last issue is a study by Windebank (1985), who found almost equal toxicity to cultures of dorsal root ganglia neurons from pyridoxine as from the other B6-vitamers (pyridoxal and pyridoxamine). This observation tended to link pyridoxine toxicity to its coenzyme function. In support of such a linkage, the three vitamers are known to be interconvertible through the activity of pyridoxine oxidase and pyridoxine kinase, yielding the active coenzyme pyridoxal 5-phosphate (McCormick and Chen, 1999). The importance of the present work is that we have demonstrated that the question of neurotoxicity by the B6- vitamers in vivo was not settled by the in vitro experiments, which found no differences among them (Windebank, 1985). Further study must include assays of each of the vitamers in serum and in the target neural tissues. The incentive for such a study is the possibility that the pyridoxine molecule itself, or a presently unsuspected metabolite, might be responsible for the neurotoxicity.
Question for the article is, how do toxic doses of pyridoxal compare to pyridoxine. I think the article is missing this clear distinction.
The article's bolded words are misleading because there is evidence that pyridoxine is much more toxic than pyridoxal.
However, some people are developing neuropathy precisely because of a long-term, accumulated multiple vitamin B deficiency.
To use the more general label "B6" is an attempt to scare people away from supplementation.
People should be less deterred from a high quality vitamin B complex (containing pyridoxal, a hydrogenated folate, cofactors etc.).
we really only have Levine “versus” Vrolijk here
several analogs of pyridoxine were neurotoxic in vitro. Those that may be converted into active coenzymes— pyridoxal, pyridoxine, and pyridoxamine— were almost equal in, toxicity. Pyridoxic acid, which is not active, was nontoxic. Pyridoxamine 5-phosphate, which cannot enter cells, also was nontoxic. Several hypotheses that link coenzyme function to toxic effect are described.Other than the cells being derived from rats, it's more relevant an experiment as we know that DRG are involved with the megavitamin-b6 syndrome, rather than cancer cells that have less causal and mechanistic relevance (even if they distally came from humans). I'm not sure what became of his work here, because he outlined several hypothesis and had some other things in press, but it doesn't look like there was much follow-up on his paper.
Dogs, rats, and rabbits were able to tolerate short-term doses of up to 1 gm/kg/day without ill effects (Unna, 1940; Unna and Antopol, 1940. Delorme and Lupien, 1976), but with higher doses or the long-term administration of as less as 200 mg/day, ataxia, muscle-weakness and progressive neurotoxicity occurred (Phillips et al. 1978). Pyridoxal is several times as toxic as the other forms of the vitamin, though its toxicity is still quite low. There is no evidence of teratogenicity (Khera, 1975) or carcinogenicity (Visek et al., 1978) from large doses of pyridoxine.
I'm looking more carefully at Nutritional Toxicology V1. While that book appears to have been published in 2012, Chapter 3 in that book, "Vitamin Excess and Toxicity" looks like it was published in 1982. Some evidence:
I believe given that it fails WP:MEDRS as it's too old and there's newer reviews. So I'm going to remove the content it supports. - Scarpy ( talk) 22:02, 17 January 2021 (UTC)
If anyone is interested, the editor for that text book, John N. Hathcock, passed away in 2019. I can't find affiliations for DR Miller or KC Hayes, so I'm not sure if we'll ever know if the bit about pyridoxal vs pyridoxine was a mistake there. Either way, still don't think it's MEDRS here. John N. Hathcock seemed like a brilliant man, though. - Scarpy ( talk) 07:53, 20 January 2021 (UTC)
@
David notMD:
Thanks for this. One small thing. The edit summary says Exceptions: deleted mention of suppressing lactation (1998 ref) as a recent systematic review (PMID 28425125) concluded clinical trial evidence inconclusive
. I think you meant
28425124 as
28425125 is way different. -
Scarpy (
talk)
09:25, 20 February 2021 (UTC)
Quick look identified a few weak or inappropriate refs. All should be looked at. David notMD ( talk) 03:07, 21 August 2021 (UTC)