Talk:Megavitamin-B6 syndrome

Notes on creation

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)

WP:MOSLEAD and WP:ISATERMFOR

Scarpy, do you think the intro has a WP:ISATERMFOR problem? Kolya Butternut (talk) 20:57, 7 February 2020 (UTC)

I wanted to establish in the lead what the most official term (e.g. the one recognized by the WHO) is because there's a lot of different language used to describe this. But would be open to wording changes here that conveyed the same point. - Scarpy (talk) 17:36, 10 February 2020 (UTC)

Would this be awkward/unclear? 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)

Kolya Butternut tweaked it a bit. Let me know what you think. - Scarpy (talk) 02:14, 13 February 2020 (UTC)

Usually but not always

@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)

If it will help people<snark> to be slightly less logical</snark> I've got no problem with it. Added it back. Thank you for the note. SchreiberBike | ⌨  23:56, 10 February 2020 (UTC)

Premenstrual syndrome and vitamin b6

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.

• 1999 - "The most recent review, published in 1999 [43], included unpublished data from authors of several of the 25 published trials of vitamin B6 and PMS. These authors also conclude that the studies suffer from several methodological problems and only one included sufficient subjects. The authors suggest that the pooled data indicate the potential for B6 to reduce PMS symptoms and may beneficially affect depression associated with PMS; however, the studies are of 'insufficient quality to draw definitive conclusions.'" They are also careful to point out "high doses of this vitamin taken for prolonged periods of time can cause neurological symptoms."

• 2011 - This article cites the same review (Wyatt KM, Dimmock PW, Jones PW, Shaughn O'Brien PM. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review. BMJ. 1999) but draws a different conclusion the the authors, so I believe it's suspect. "One systematic review of nine RCTs suggests pyridoxine (vitamin B6) supplementation relieved PMS symptoms by more than twofold compared with placebo (odds ratio = 2.32; 95% confidence interval, 1.95 to 2.54).23 Because doses higher than 100 mg showed no greater response than doses below 100 mg,23 and high doses of pyridoxine (greater than 300 mg) may be associated with peripheral neuropathy, moderate-dosage (i.e., 50 to 100 mg per day) vitamin B6 supplementation could be considered for relieving PMS symptoms and premenstrual depression with minimal risks of adverse effects."

• 2003 - this also cites Wyatt 1999.
• in 2000 Wyatt also published Poor-quality studies suggest that vitamin B6 use is beneficial in premenstrual syndrome but did find some high quality studies mentioned in the article that show effectiveness.

• 2007 - "Positive evidence was also found for vitamin B6. A systematic review to evaluate the efficacy of vitamin B6 for the treatment of PMS identified 25 published trials and included nine trials, representing 940 patients (Wyatt et al., 1999). The overall odds ratio for efficacy of B6 was 2.32 (1.95–2.54). Wyatt et al. suggest that doses of vitamin B6 up to 100 mg/day may benefit premenstrual depression and other symptoms. However, conclusions from the meta‐analysis were limited by the methodological weaknesses of some of the trials included. Findings from studies assessing vitamin B6 in this review are also mixed, although studies which demonstrated benefits appeared to be methodologically stronger. The evidence suggests that continuous vitamin B6 treatment at doses of 50 to 150 mg/day may be beneficial for some PMS symptoms, since the intermittent treatment (at 50 to 300 mg/day) did not prove effective (Diegoli et al., 1998; Mal mgren et al., 1987; Stokes & Mendels., 1972). However, more trials, using stricter diagnostic criteria, are required to confirm its benefit."
• 2003 - "In nine randomized, controlled clinical trials of vitamin B6 as a single supplement or in a multivitamin, improvement of symptoms was reported, but the poor quality of the trials limits their usefulness.16 [Evidence level B, systematic review of lower quality randomized controlled trials (RCTs)] Vitamin B6 should not be routinely recommended for women with PMS.1,4,16"
• Wyatt's 1999 paper - https://www.bmj.com/content/318/7195/1375.short
• 2003 - see table 2 ("Likely Yes").
• 2017 - this finds an effect, but is in a a really really bad journal.
• 2010 - finds a better than placebo effect with magnesium and vitamin b6, but this is also in a really bad journal. Looks like it was republished here. And a similar one here
• 2006 - no difference between placebo and b6.
• 2009 - only calcium was found to be effective, vitamin b6 may be effective but did not have good quality studies.
• 1986 - this is old but interesting because it was looking at serum b6 levels in people who experience PMS and people who don't. no difference there.
• 2013 aerobic exercise and b6 worked better than controls, but this is a complementary medicine journal.
• 2004 - low vitamin b6 is associated with depression, but says nothing about treating depression with vitamin b6
• 2011 - no association with b6 intake.
• 2002 - inconclusive evidence for b6.

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)

Pyridoxine vs pyridoxal

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)

First of all, I highly appreciate the fact that you originated this article, because neuropathy isn't a pleasant thing to have! However, some people are developing neuropathy precisely because of a long-term, accumulated multiple vitamin B deficiency. Question for the article is, how do toxic doses of pyridoxal compare to pyridoxine. I think the article is missing this clear distinction. My issue is that this article currently paints one a bit too much with the brush of the other. People should be less deterred from a high quality vitamin B complex (containing pyridoxal, a hydrogenated folate, cofactors etc.).

I will stand corrected on this whole issue if [see point 3]. If so, it will also be of importance to some people in my personal life so I care for the truth.

1. The article's bolded words are misleading because there is evidence that pyridoxine is much more toxic than pyridoxal. Most articles, on toxicity that is, mention pyridoxine in their title. To use the more general label "B6" is an attempt to scare people away from supplementation. Whether that's a good thing is not what I want to discuss, nor whether you think this is a fair analysis (I'm not saying it is done with evil intent). But it is still a subtle form of misinformation or at least imprecision. Industrially, a substance is manufactured to act in stead of a vitamin; the ill effects of said substance then infect and damage the name of the target vitamin (which is a different molecule!).
2. With synthetic I mean pyridoxine specifically as opposed to forms of pyridoxal and pyridoxamide, because the most common synthetic form is the former. I do not mean that there is a difference between synthetic [any molecule] and natural [same molecule]. I care to discuss about molecular structure only.
3. I would genuinely be very interested in sources about toxicity of pyridoxal. Question for the article is, how do toxic doses of pyridoxal compare to pyridoxine. I think the article is missing this clear distinction.
4. understand
5. I think either Vrolijk or another reference cited Dalton and Dalton in such words.

2A02:181F:0:80A7:E853:1641:F6FC:942F (talk) 16:25, 14 January 2021 (UTC)

Taking these in reverse order.

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.

Wilmshurst, Jo M.; Ouvrier, Robert A.; Ryan, Monique M. (2019). "Peripheral nerve disease secondary to systemic conditions in children". Therapeutic Advances in Neurological Disorders. 12: 175628641986636. doi:10.1177/1756286419866367. PMC 6691669. PMID 31447934. this says 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 required note 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.

John Hathcock (2 December 2012). "Chapter 3. Vitamin Excess and Toxicity". Nutritional Toxicology. Elsevier. pp. 110–111. ISBN 978-0-323-14693-7. this text book contradicts the 2017 article, the author believes that pyridoxial is worse than alternatives : 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.

Levine, Seymour; Saltzman, Arthur (2004). "Pyridoxine (vitamin B₆) neurotoxicity: enhancement by protein-defcient diet". Journal of Applied Toxicology. 24 (6): 497–500. doi:10.1002/jat.1007. ISSN 0260-437X. PMID 15558839. S2CID 8280774. this study is in mice, but the results still aren't clear and it seems like different vitamers may cause different side-effects ...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.

This is not a question for the article, this is a question for people researching vitamin b6 toxicity and publishing in peer-reviewed journals. Wikipedia is here to give an encyclopedic summary of what's in the peer-reviewed medical literature (with a preference in this case towards reviews), not to do original research.

The article's bolded words are misleading because there is evidence that pyridoxine is much more toxic than pyridoxal.

The ICD calls it Megavitamin-B6 syndrome, not Mega-pyridoxine syndrome. Pyridoxine is also often used as shorthand for b6 vitamers in many of these papers.

Regarding your points on supplementation:

However, some people are developing neuropathy precisely because of a long-term, accumulated multiple vitamin B deficiency.

Even people in "professions" full of quacks (e.g. functional medicine) know that b6 deficiency is extremely rare. Other than rare medical conditions (many of which are mentioned in this article) why would anyone need to exceed the most conservative 10mg TUL set by the NHS in any form?

Even the studies that are suggesting to increase it are only saying a few more milligrams are needed (e.g. A recent U.S. study, which tested the blood PLP levels in around 8,000 patients, demonstrated a widespread deficiency of the vitamin among all tested subgroups, and the authors suggested an increase of the daily allowance from around 2 mg to 3 to 4.9 mg per day).

To use the more general label "B6" is an attempt to scare people away from supplementation.

It's not.

People should be less deterred from a high quality vitamin B complex (containing pyridoxal, a hydrogenated folate, cofactors etc.).

This makes me worried that you have a conficlit of interest. Wikipedia isn't here to do marketing for the supplement industry.

The TULs established by various agencies are listed as they are stated in their sources.

If supplement aficionados want to claim that one form is definitively safer than another, they can start by conducting at least one properly designed randomized controlled trial and publishing their results in a reputable journal. Until then--the summary of what we know about the vitamers is there, and the TULs are listed and the sources are cited.

Giving people a false impression that other b6 vitamers have been determined to be entirely safe would be original research. - Scarpy (talk) 05:45, 15 January 2021 (UTC)

Thank you for reproducing these sources.

Too bad there’s so little known about pyridoxal – we really only have Levine “versus” Vrolijk here (Hathcock cites no source for the last sentence; Wilmshurst cites Vrolijk). I have searched and could only find citations back to these two.

However, I cannot expect from you to continue this discussion with me. I now understand that Wikipedia is not a place for discussion or original research, but for summarizing the most authoritative sources (preferably reviews and textbooks). In that respect I have wasted your time. Please forgive me and thanks for taking the time to explain regardless – it is going to help me.

PS I have a background in chemistry (though not in biochemistry) and am studying the literature as an amateur. I hope I can alleviate your worries as I have no conflict of interest, have no clients, sell nothing, am not an ‘influencer’. 2A02:181F:0:80A7:547D:53E4:919:F3BF (talk) 13:22, 15 January 2021 (UTC)

Thanks. Appreciate it. Not a waste of my time at all. I am a bit grizzled as there's a lot of misinformation and disinformation in this space and, like you, I want to prevent people from needlessly developing neuropathy. Two quick clarifications.

we really only have Levine “versus” Vrolijk here

Levine is a bit confounding in the case of this article because it's discussing acute toxicity and neurotoxicity at different times.

It's worth reading the entire Vrolijk study. They tested b6 vitamers with two forms of cells, SHSY5Y and Caco-2 cells (both cancer cell lines). The effect was limited to pyridoxine on SHSY5Y cells, the CaCo-2 weren't effected. I'm not sure if they're aware that pyridoxine is sometimes paired with cisplatin (which also causes neuropathy) to improve the efficacy of the cisplatin in inhibiting cancer growth. From the cisplatin-related research pyridoxine's in vitro effect on some cancers is not too surprising.

The more interesting contrast is Windebank 1985 (cited in Levine) that tested b6 vitamers with model dorsal root ganglion cells from rats. 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.

I agree the Hathcock text isn't clear. 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.

looking at what's cited in that same paragraph we have:

Delorme, C. B., and Lupien, P. J. (1976). The effect of a long-term excess of pyridoxine on the fatty acid composition of the major phospholipids in the rat. J. Nutr. 106, 976. - not here

Khera, K.S. (1975). Teratogenicity study in rats five high doses of pyridoxine (vitamin B6) during organogenesis. Experientia 31, 469. - not here

Unna, K. (1940). Toxicity and pharmacology of vitamin B6. J. Physiol. 40, P483. - can't find this specifically although it seems to be cited in some other journals, and there was a paper with a nearly identical title in another journal. at any rate, it doesn't seem they're doing a comparison between the vitamers.

Unna, K. and Antopol W. (1940). Toxicity of vitamin B6. Proc. Soc. Exp. Biol. Med. 43, 116. - not here.

Visek, W. J., Clinton, S. K. and Truex, C. R. (1978). Nutrition and experimental carcinogenesis. Cornell Vet. 68, 3. - not here

Phillips et al. 1978 was missing from the Google Books preview, but I'm 99% sure it's Subacute toxicity of pyridoxine hydrochloride in the beagle dog. - not here

I'm tempted to see if I can contact the author and ask where he got that information from. - Scarpy (talk) 21:20, 17 January 2021 (UTC)

Thank you. Windebank is a very interesting source, all the more so for the reasons you clarified, even if it is somewhat old and hasn't been followed up. This puts the case to rest in my mind that pyridoxal has considerable probability of being as toxic as pyridoxine until new studies indicate otherwise. 2A02:181F:0:80A7:853E:7374:9DBB:AAAF (talk) 11:50, 28 January 2021 (UTC)

Nutritional Toxicology V1

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:

• On the first page of the chapter a copyright notice appears that reads: Copyright 1982 by Academic Press, Inc. / All rights of reproduction in any form reserved. / ISBN 0-12-332601-X
• Looking up than ISBN, it looks like there's been various printing and publishing since 1982
• That chapter doesn't appear to have been updated. If you skim the references, I can't find one that's newer than 1980.
• Also appears to be true looking at the scholar cluster: https://scholar.google.com/scholar?cluster=15312689725852957300&hl=en&as_sdt=0,6
• It's been cited plenty of times before 2012.

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)

Suppressing lactation

@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)

Yes. David notMD (talk) 10:50, 20 February 2021 (UTC)

Needs a check of all refs

Quick look identified a few weak or inappropriate refs. All should be looked at. David notMD (talk) 03:07, 21 August 2021 (UTC)

@David notMD: I'm not a doctor, but I was pretty careful here and had reasons for all of these. Looking at the refs removed there's:

- Bell, Daniel J. "Vitamin B₆ excess". Radiopaedia. Archived from the original on 2019-10-24. Retrieved 2019-12-01.

- Silva, C D; D'Cruz, D P (2006). "Pyridoxine toxicity courtesy of your local health food store". Annals of the Rheumatic Diseases. 65 (12): 1666–1667. doi:10.1136/ard.2006.054213. ISSN 0003-4967. PMC 1798481. PMID 17105856.

- Callizot, Noëlle; Poindron, Philippe (2008). "Pyridoxine-Induced Peripheral Neuropathy". New Animal Models of Human Neurological Diseases. Biovalley Monographs. pp. 66–80. doi:10.1159/000117724. ISBN 978-3-8055-8405-0.

My thoughts here are:

Radiopedia ties together a lot of the various names for mega-b6 syndrome, and that's all it's used for. I think that's reasonable here.

MEDRS in a nutshell says cite reviews, don't write reviews. Silva 2006 is a pretty good review/summary, and Annals of the Rheumatic Diseases is at the moment is the best Rheumatology journal based on CiteScore (and the third for General Biochemistry, Genetics and Molecular Biology) https://www.scopus.com/sourceid/19136

Callizot 2008 has 'animals' in the subtitle, but discusses and reviews the literature on mega-b6 in humans. I don't think the way this is cited and used runs afoul of WP:MEDANIMAL. - Scarpy (talk) 06:31, 21 August 2021 (UTC)

@David notMD: - I added some quotes to the citations to help clarify their purpose in the article. - Scarpy (talk) 00:04, 26 August 2021 (UTC)