User talk:Scarpy/Vitamin B6 Toxicity

Sources found and not used
I did a very thorough check of all the literature related to Megavitamin-B6 syndrome, most of it didn't make the cut for the article, but I've included a list of everything I cut out and tried to indicate why.

Sources/facts More appropriate in vitmain b6 article

 * "Most of the absored nonphosphorylated vitamin b6 goes to the liver, and certain forms of the vitamin (pyridoxal, pyridoxine, and pridoxamine) are converted to their respective 5'-phosphates by pyruddoxial kinase. Vitamin B6 can be bound to proteins in tissues, which limits accumulation at very high intakes. When this capacity is exceeded, nonphosphorylated forms of vitamin b6 are released by the liver and other tissues in to the circulation.A At pharmacological doses of vitamin b6 high amounts accumulate in the muscle, plasma and erythrocytes when other tissues are saturated... Most of the body's vitamin b6 is found in the muscle; the muscle pool of the vitamin appears to very slowly turn over. Vitamin B6 is oxidized in the liver and then released and primarily excreted in the urine." in
 * "some studies have suggested that increased levels of the B6 vitamers and some derivatives can generate toxic photoproducts as a result of UV irradiation [121,122,123]." in
 * ("These data provide further confirmation that the vitamin B-6 pools in skeletal muscle are resistant to depletion. They also demonstrate that in humans with constant body weight, vitamin B-6 supplementation is not associated with marked increases in vitamin B-6 in muscle.")
 * (tissue distribution [muscle, liver, brain, etc] and exercise)
 * "Of circulating vitamin B6, 60 % is PLP [1]. The half-life of pyridoxine is up to 20 days. The major inactive metabolite 4-pyridoxal acid is excreted in the urine [5]." in
 * "Steroid hormone action.... Over the last 15 years a completely new function of vitamin B6 has been discovered; in regulating the actions of steroid hormones such as the oestrogens, progesterone and testosterone. These hormones all act by entering the cells of target tissues and binding to a receptor protein in the nucleus which then binds to DNA and regulates the expression of genes. Pyridoxal phosphate specifically binds to the hormone receptor protein in the nucleus and displaces it from DNA binding, so terminating the action of the hormone.... In vitamin B6 deficiency there is increased and prolonged retention of steroid hormones in the nucleus, together with increased responsiveness of target tissues to the actions of low concentrations of hormones. Conversely, concentrations of vitamin B6 greater than those normally found in tissues lead to reduced sensitivity to hormone action (Allgood and Cidlowski, 1992; Bender, 1987, 1994).... Although most of the body’s vitamin B6 is in muscle, associated with glycogen phosphorylase, this pool of the vitamin is only metabolized slowly; it is the 20 per cent of the total body content involved in amino acid metabolism and steroid hormone action that is metabolized rapidly. In studies of vitamin B6 requirements in which volunteers are deprived of the vitamin until specific biochemical signs of deficiency develop, and are then repleted with graded doses of the vitamin, it is found that depletion occurs faster, and repletion requires a higher intake, when the subjects are fed a high protein diet. Estimates of average requirements are therefore related to protein intake, and the reference nutrient intake (RNI) is based on 15µg of vitamin B6 per gram of dietary protein (Bender, 1989; Department of Health, 1991). This leads to RNIs for adults of between 1.4‐2.0mg/day (see Table I). For nutritional labelling of foods, the reference intake is 2.0mg/day.... High intakes of vitamin B6 supplements can lead to nerve damage. Schaumburg et al. (1983) reported the development of peripheral sensory neuropathy in seven patients who had been taking supplements of vitamin B6 in excess of 1g/day for several months. When the supplements were withdrawn, the patients showed some recovery of nerve function, but there was persistent damage in some cases....
 * "stored in tissue, amount 50mg to 150mg (total stored in body, muscle, brain, liver, etc)." also regarding b12 page 234, b12 is so safe that it's sometimes used as a placebo (it has a red color in transparent syringes), and it's intestinal uptake is limited so dosages of several hundred times the nutritional requirements are safe.

https://scholar.google.com/scholar?hl=en&as_sdt=0%2C6&q=b6+rda+“4.2”&btnG=#d=gs_qabs&u=%23p%3DLxLc9bnnDl8J Scarpy (talk) 17:32, 15 January 2020 (UTC)

Gene-related and experimental treatments

 * (NRT-3, borderline)
 * (NT-3 also protects against many of the features of pure large-fibre sensory neuropathy induced by pyridoxine (PDX) (vitamin B6) overdose)
 * (NT-3 also protects against many of the features of pure large-fibre sensory neuropathy induced by pyridoxine (PDX) (vitamin B6) overdose)
 * (NT-3 also protects against many of the features of pure large-fibre sensory neuropathy induced by pyridoxine (PDX) (vitamin B6) overdose)

Cited in reviews

 * Dordain G, Deffond D. Neuropathies à la pyridoxine. Revue de la littérature. Thérapie 1994; 49:333–337
 * (cited in the 9.6g/day paper)
 * Dordain G, Deffond D. Neuropathies à la pyridoxine. Revue de la littérature. Thérapie 1994; 49:333–337
 * (cited in the 9.6g/day paper)
 * Dordain G, Deffond D. Neuropathies à la pyridoxine. Revue de la littérature. Thérapie 1994; 49:333–337
 * (cited in the 9.6g/day paper)
 * (cited in the 9.6g/day paper)
 * (cited in the 9.6g/day paper)
 * (cited in the 9.6g/day paper)
 * (cited in the 9.6g/day paper)
 * (cited in the 9.6g/day paper)

Historic or seminal

 * ("Doses less than 500 mg/day appear to be safe on the basis of literature reports where the compound was administered for periods ranging from 6 months to 6 years.")
 * ("... but with higher doses or the long-term administration of as little as 200mg/day, ataxia, muscle weakness, and progressive neurotoxicity occurred.")
 * ("Furthermore, there appears to be an inverse relationship between the dose and the time up to the occurrence of toxic symptoms.")
 * (this might be the first coasting paper)
 * Very high doses were also found to be well-tolerated as a treatment for Unsymmetrical dimethylhydrazine (UDMH) intoxication. in
 * ("Doses less than 500 mg/day appear to be safe on the basis of literature reports where the compound was administered for periods ranging from 6 months to 6 years.")
 * ("... but with higher doses or the long-term administration of as little as 200mg/day, ataxia, muscle weakness, and progressive neurotoxicity occurred.")
 * ("Furthermore, there appears to be an inverse relationship between the dose and the time up to the occurrence of toxic symptoms.")
 * (this might be the first coasting paper)
 * Very high doses were also found to be well-tolerated as a treatment for Unsymmetrical dimethylhydrazine (UDMH) intoxication. in
 * (this might be the first coasting paper)
 * Very high doses were also found to be well-tolerated as a treatment for Unsymmetrical dimethylhydrazine (UDMH) intoxication. in
 * (this might be the first coasting paper)
 * Very high doses were also found to be well-tolerated as a treatment for Unsymmetrical dimethylhydrazine (UDMH) intoxication. in

Animal studies

 * (study on chicks showing effect of toxicity but only tangentially related)
 * (study on piglets)
 * (study on piglets)
 * (study on dogs)
 * (reduces the effects of alcohol in rats)
 * (maze performance of rats)
 * (falcons, this one is super sad)
 * (in rats, and mentioned in other sources)

Amount in foods

 * http://www.whfoods.com/genpage.php?tname=nutrient&dbid=108#foodchart
 * foods
 * more foods

Details on B6 metabolism not directly related

 * (excellent summary of b6 metabolism, but not directly on topic)
 * (mentions "b6 accumulates in the muscle "At pharmacological doses of vitamin b6, high amounts accumulate in the muscle, plasma, and erythrocytes with other tissues are saturated. Most of the body's vitamin b6 is found in the muscle; the muscle pool of the vitamin appears to very slowly turn over. Vitamin B6 is oxidized in the liver and then released and primarily excreted in the urine." but I don't see much direct relevance here)
 * (PLP increased following exercise for a 20-50 minutes, then returned to baseline after 30 minutes -- other very interesting tidbits about exercise and diet and b6. mentions b6 stored in the liver?)
 * (more on b6 and liver)
 * (mentions "b6 accumulates in the muscle "At pharmacological doses of vitamin b6, high amounts accumulate in the muscle, plasma, and erythrocytes with other tissues are saturated. Most of the body's vitamin b6 is found in the muscle; the muscle pool of the vitamin appears to very slowly turn over. Vitamin B6 is oxidized in the liver and then released and primarily excreted in the urine." but I don't see much direct relevance here)
 * (PLP increased following exercise for a 20-50 minutes, then returned to baseline after 30 minutes -- other very interesting tidbits about exercise and diet and b6. mentions b6 stored in the liver?)
 * (more on b6 and liver)

Other not directly related, or not most apt

 * https://neuropathycommons.org/neuropathy/neuropathy-overview
 * https://www.news-medical.net/health/Neuronopathy-and-neuropathy-Whats-the-difference.aspx
 * (super interesting, but not useful in the article)
 * (hypophosphatasia)
 * (hypophosphatasia)
 * (“ 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 [30]”)
 * (hypophosphatasia)
 * (hypophosphatasia)
 * (“ 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 [30]”)
 * (“ 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 [30]”)
 * (“ 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 [30]”)
 * (“ 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 [30]”)
 * (“ 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 [30]”)


 * https://radar.avrotros.nl/uitzendingen/gemist/item/uitzending-05-09-2016/ (video)
 * https://radar.avrotros.nl/uitzendingen/gemist/item/radar-checkt-verbod-op-schadelijke-vitamine-b6-doseringen/
 * https://radar.avrotros.nl/nieuws/item/nvwa-brengt-verbod-uit-voor-pillen-met-teveel-vitamine-b6/
 * https://web.archive.org/web/20191202202107/https://www.tga.gov.au/committee-meeting-info/cmec-meeting-66-18-april-2008
 * https://ods.od.nih.gov/Health_Information/ODS_Frequently_Asked_Questions.aspx#Brands
 * Office of Dietary Supplements - Vitamin B6 - Consumer
 * https://browser.ihtsdotools.org/?perspective=full&conceptId1=440741000124109&edition=MAIN&release=&languages=en
 * http://bioportal.bioontology.org/ontologies/SNOMEDCT/?p=classes&conceptid=http%3A%2F%2Fpurl.bioontology.org%2Fontology%2FSNOMEDCT%2F724558003
 * http://bioportal.bioontology.org/ontologies/SNOMEDCT?p=classes&conceptid=http%3A%2F%2Fpurl.bioontology.org%2Fontology%2FSNOMEDCT%2F238146000
 * https://patient.info/doctor/hypervitaminosis#nav-4
 * ("Differential diagnoses such as adrenal insufficiency were ruled out, but biochemical analysis demonstrated unusual high pyridoxine serum levels (vitamin B6). History revealed the intake of 300 mg of vitamin B6 per day over 6 months as described by her general practitioner. All symptoms disappeared after the discontinuation of vitamin B6 supplementation. Importantly, in contrast to many other vitamins and supplements, there is no evidence in the literature of the occurrence of vitamin B6 deficiency after bariatric surgery. Therefore, supplementation of vitamins and supplements in bariatric patients has to be carefully considered according to the existing clinical guidelines, as uncritical oversupplementation of micronutrients might result in intoxication and serious illness as presented here.")
 * (not directly related)
 * (was discussed in the Australian parliment, found the source referenced)
 * (not sure about the WP:MEDRS status here, but LPI strikes me as borderline)
 * (this was removed soon after it was posted, and only breifly mentioned vitamin b6 toxicity though commented that it's associated with energy drinks)
 * https://www.mayoclinic.org/drugs-supplements-vitamin-b6/art-20363468 (not detail enough, apparently there was an older version of this with more warnings about b6 toxicity).
 * https://www.ncbi.nlm.nih.gov/books/NBK3981/table/a20015f31ttt00182/?report=objectonly (shows supplement use by members of the miliary and discusses some correlates).
 * http://urologyjournal.org/index.php/uj/article/view/3808 (impact on semen quality, not directly relevant here)
 * Bernstein AL. Vitamin B6 in clinical neurology. Ann N Y Acad Sci 1990;585:250-260.
 * (interesting single case study, no significant review)
 * ("Patients with chronic renal failure receiving home parenteral nutrition, HPN, with multivitamins may develop elevated pyridoxine levels, which might result in neurologic sequelae." this is interesting, but I don't it could be included without running a foul of WP:SYN)
 * (there's a bit in here about Isoniazid, INH, isonicotinic hydrazide poisioning, but I don't think it's relevant).
 * (fantastic 2001 article on TUL and failure to recognize them, but I don't believe it's a good source for anything here).
 * (appears to be more about the testing method than anything else)
 * (very good discussion of megavitamin therapy)
 * very good discussion of all things b-vitamin, including tolerable upper limits (TULs) on folate, niacin and b6. Notes "The final B vitamin with an ascribed upper limit is vitamin B6 which has an upper limit set at 100 mg/day (approximately 75 × RDA) in the US on the basis of case reports of reversible sensory neuropathy following doses in excess of 1000 mg taken for extended periods. However, it is notable that multiple clinical trials entailing consuming up to 750 mg/day of vitamin B6 for a number of years have demonstrated a lack of neuropathic side effects [15]." ... don't know that it's relevant here.
 * ("On the basis of our prospective case–control study and review of the literature, an association between CIAP and vitamin B6 exposure or elevated vitamin B6 levels appears unlikely.")
 * (worst case 600mg/day 3-10 years, dozens of times the UL)
 * (PLP increases during exercise, is insignificant in sweat).
 * (fantastic 2001 article on TUL and failure to recognize them, but I don't believe it's a good source for anything here).
 * (appears to be more about the testing method than anything else)
 * (very good discussion of megavitamin therapy)
 * very good discussion of all things b-vitamin, including tolerable upper limits (TULs) on folate, niacin and b6. Notes "The final B vitamin with an ascribed upper limit is vitamin B6 which has an upper limit set at 100 mg/day (approximately 75 × RDA) in the US on the basis of case reports of reversible sensory neuropathy following doses in excess of 1000 mg taken for extended periods. However, it is notable that multiple clinical trials entailing consuming up to 750 mg/day of vitamin B6 for a number of years have demonstrated a lack of neuropathic side effects [15]." ... don't know that it's relevant here.
 * ("On the basis of our prospective case–control study and review of the literature, an association between CIAP and vitamin B6 exposure or elevated vitamin B6 levels appears unlikely.")
 * (worst case 600mg/day 3-10 years, dozens of times the UL)
 * (PLP increases during exercise, is insignificant in sweat).
 * (worst case 600mg/day 3-10 years, dozens of times the UL)
 * (PLP increases during exercise, is insignificant in sweat).

Unreliable by Wikipedia standards, but memorable

 * https://b6toxicity.blogspot.com/
 * https://wholefoodcatalog.info/nutrient/vitamin_b6(pyridoxine)/foods/low/
 * http://apjcn.nhri.org.tw/server/info/books-phds/books/foodfacts/html/data/data4d.html
 * https://www.medhelp.org/posts/Nutrition/B6-Toxicity/show/2642
 * https://www.medhelp.org/forums/Vitamin-B6-Toxicity/show/864
 * https://nutritiondata.self.com/
 * https://www.reddit.com/r/Nootropics/comments/anxznv/toxic_b6_levels/
 * https://gm.eatatsalt.com/4279-vitamin-b6.html (unreliable source. mentions hives)
 * https://www.neurotalk.org/vitamins-nutrients-herbs-and-supplements/30724-vitamin-b6-pyridoxine-5-information.html
 * https://www.reddit.com/r/DrSteve/comments/40nyg7/mutated_strain_of_e_coli_produces_extreme_amounts/
 * http://www.charlesbeaman.com/neurologyboardreview (classifies hypervitaminosis b6 as a Dorsal root ganglion disorder, but not sure about the WP:RSness of the source)
 * https://www.livestrong.com/article/522968-how-to-lower-b6/ (according to Memorial Sloan-Kettering Cancer Center. Typically, it takes the body between 15 and 25 days to eliminate unused pyridoxine.)
 * http://epilepsygenetics.net/2014/04/02/hidden-neurometabolic-disorders-the-expanding-spectrum-of-pnpo-deficiency/
 * https://lifewithb6.blogspot.com/

Alternative medicine journals

 * https://pdfs.semanticscholar.org/5416/9a335195f47e1d51108b80522a63f7d78b2d.pdf
 * http://www.orthomolecular.org/library/jom/2003/pdf/2003-v18n02-p065.pdf

May be used in the future

 * https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764703/ - 2020
 * https://pastebin.com/zy0nB9MH
 * https://cot.food.gov.uk/sites/default/files/cot/vitb6tox.pdf
 * https://www.sbrc.ca/2017/01/study-finds-drugs-that-can-reverse-nerve-damage/
 * https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086960/
 * https://www.fiercebiotech.com/research/peripheral-neuropathy-could-be-reversed-by-fda-approved-class-drugs
 * https://search.proquest.com/docview/1794010616?pq-origsite=gscholar
 * https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2758742 (b12 study)
 * https://performancerehabnj.com/services/neuropathy/
 * https://ltd.aruplab.com/Tests/Pub/0080111


 * https://patents.google.com/patent/US8017403B2/en

Hypovolemia

 * https://www.sciencedirect.com/science/article/abs/pii/S1567424X09704386
 * https://www.nejm.org/doi/full/10.1056/NEJM200010053431404

Cisplatin

 * https://scholar.google.com/scholar?start=20&q=pyridoxine+Cisplatin&hl=en&as_sdt=0,6



Image search

 * https://kcpain.com/dorsal-root-ganglion-stimulation/
 * http://www.neuronexperts.com/neuropharmacology/neuropathies-demyelinating-diseases/
 * https://www.researchgate.net/figure/Cresyl-violet-staining-of-the-dorsal-root-ganglion-DRG-in-the-control-a_fig6_289366812
 * NEW: https://bmcneurosci.biomedcentral.com/articles/10.1186/s12868-020-00559-3
 * NEW: https://www.researchsquare.com/article/rs-7796/v1 (CC)
 * https://www.sciencedirect.com/science/article/pii/S030645221500041X
 * NEW: https://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=1;spage=162;epage=168;aulast=Cho
 * https://www.nrronline.org/viewimage.asp?img=NeuralRegenRes_2020_15_1_162_264472_f5.jpg
 * https://www.researchgate.net/figure/A-Normal-dorsal-funiculus-in-L4-B-Dorsal-funiculus-in-L4-showing-disruption-and_fig2_5362446 (CC)
 * https://jps.biomedcentral.com/articles/10.1007/s12576-019-00659-8
 * https://www.researchgate.net/figure/Histopathological-evaluation-of-dorsal-Root-Ganglion-neurons-in-the-treatment-and-control_fig1_253649036 (CC)
 * https://www.nature.com/articles/s41467-019-13839-2
 * NEW: https://journals.sagepub.com/doi/pdf/10.1177/0192623319826068
 * https://www.jneurosci.org/content/17/1/372
 * https://zenodo.org/record/1258933/files/article.pdf


 * https://www.mdpi.com/1422-0067/22/14/7417/htm (bogus?)
 * https://www.medlink.com/articles/pyridoxine-deficiency-and-toxicity


 * https://n.neurology.org/content/39/8/1077


 * https://www.nejm.org/doi/full/10.1056/nejm198308253090801


 * NEW: https://practicalneurology.com/articles/2020-jan/neuromuscular-notes-neuronopathies


 * NEW: https://journals.physiology.org/doi/full/10.1152/jn.00739.2019


 * NEW: https://www.nature.com/articles/s41467-019-13839-2


 * NEW: https://www.hindawi.com/journals/prm/2020/3740162/


 * https://link.springer.com/chapter/10.1007/978-1-4614-6567-6_23


 * https://www.sciencedirect.com/topics/neuroscience/dorsal-root-ganglion


 * https://cp.neurology.org/content/5/6/509
 * https://pn.bmj.com/content/14/4/242
 * https://www.thelancet.com/journals/laneur/article/PIIS147444220570096X/fulltext
 * https://rapm.bmj.com/content/45/2/137 (sonic)
 * https://www.frontiersin.org/articles/10.3389/fncel.2019.00271/full


 * https://neuropathycommons.org/neuropathy/causes-neuropathy/management-nutritional-and-toxic-neuropathies


 * https://journals.physiology.org/doi/full/10.1152/jn.00739.2019
 * https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1533-2500.2002.02011.x
 * https://www.merckmanuals.com/professional/neurologic-disorders/peripheral-nervous-system-and-motor-unit-disorders/overview-of-peripheral-nervous-system-disorders

New

 * https://n.neurology.org/content/96/15_Supplement/5222?fbclid=IwAR3Mbma15lwFsE6JVh8wtDth85TSfdaKevdhHXSsQ9PhA6gwGKzM0Ey_MEQ
 * https://emerypharma.com/wp-content/uploads/2021/09/B6-Citizen-Petition-Final-.pdf?fbclid=IwAR3bUrRUTEm4ZpZxZWoXQa2oWxuxZ8SdgGwRcNrJ7B-80UInHancXTbtvWE
 * https://www.therapath.com/services/small-fiber-neuropathy-testing/small-fiber-neuropathy-overview/?fbclid=IwAR131xxXlBhV4C6KZdjoZmxse9UOzhgPehIHLY97QLd-c9ldKxZC26WTjdo
 * https://n.neurology.org/content/94/15_Supplement/4364

Missed?

 * http://hopefulgeranium.blogspot.com/2013/02/pyridoxine-toxicity-and-deficiency-and.html