Editing Vitamin B6

{{Short description|Class of chemically related vitamins}}
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{{About|the group of [[vitamers]]|the dietary supplement|Pyridoxine}}
{{Good article}}
{{DISPLAYTITLE:Vitamin B<sub>6</sub>}}
{{Use mdy dates|date=February 2024}}
{{Infobox drug class
| Name              = Vitamin B<sub>6</sub>
| Image             = Pyridoxal-phosphate.svg
| ImageClass        = skin-invert-image
| Alt               = The chemical structure of pyridoxal phosphate, a form of vitamin B<sub>6</sub>.
| Caption           = [[Pyridoxal phosphate|Pyridoxal 5'-phosphate]], the metabolically active form of vitamin B<sub>6</sub>
| Use               = Vitamin B<sub>6</sub> deficiency
| Biological_target = enzyme cofactor
| ATC_prefix        = A11H
| MeshID            = D025101
| Drugs.com         = {{Drugs.com|international|vitamin-b6}}
| Consumer_Reports  =
| medicinenet       =
| rxlist            =
<!-- not a parameter in Drug Class:
| CAS Number        = 8059-24-3 <ref>{{cite web|url=http://www.commonchemistry.org/ChemicalDetail.aspx?ref=8059-24-3|title=Vitamin B<sub>6</sub>; CAS Registry Number: 8059-24-3|publisher=CAS, American Chemical Society|date=May 2015|access-date=June 12, 2018}}</ref> -->
}}
'''Vitamin B<sub>6</sub>''' is one of the [[B vitamins]], and is an [[essential nutrient]] for humans.<ref name=ODS>{{cite web |url=http://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/ |title=Facts about Vitamin B<sub>6</sub> Fact Sheet for Health Professionals |date=February 24, 2020 |website=Office of Dietary Supplements at [[National Institutes of Health]] |access-date=February 5, 2021 |archive-date=April 18, 2011 |archive-url=https://web.archive.org/web/20110418121414/http://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/ |url-status=live }}</ref><ref name="lpi" /><ref name=PKIN2020B6 /><ref name="DRItext" /> The term essential nutrient refers to a group of six chemically similar compounds, i.e., "[[vitamer]]s", which can be interconverted in biological systems. Its active form, [[pyridoxal phosphate|pyridoxal 5′-phosphate]], serves as a [[coenzyme]] in more than 140 [[enzyme]] reactions in [[amino acid]], [[glucose]], and [[lipid]] metabolism.<ref name=ODS/><ref name="lpi">{{cite web|url=http://lpi.oregonstate.edu/mic/vitamins/vitamin-B6|title=Vitamin B<sub>6</sub> | date=May 2014|publisher=Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR|archive-url=https://web.archive.org/web/20180314160823/http://lpi.oregonstate.edu/mic/vitamins/vitamin-B6|archive-date=March 14, 2018|url-status=live|access-date=March 7, 2017}}</ref><ref name=PKIN2020B6 />

Plants synthesize pyridoxine as a means of protection from the [[UV-B|UV-B radiation]] found in sunlight<ref name="Havaux2009"/> and for the role it plays in the synthesis of [[chlorophyll]].<ref name="Parra2018"/> Animals cannot synthesize any of the various forms of the vitamin, and hence must obtain it via diet, either of plants, or of other animals. There is some absorption of the vitamin produced by [[intestinal bacteria]], but this is not sufficient to meet dietary needs. For adult humans, recommendations from various countries' food regulatory agencies are in the range of 1.0 to 2.0 [[milligram]]s (mg) per day. These same agencies also recognize ill effects from intakes that are too high, and so set safe upper limits, ranging from as low as 12&nbsp;mg/day to as high as 100&nbsp;mg/day depending on the country. Beef, pork, fowl and fish are generally good sources; dairy, eggs, mollusks and crustaceans also contain vitamin B<sub>6</sub>, but at lower levels. There is enough in a wide variety of plant foods so that a [[vegetarian]] or [[vegan]] diet does not put consumers at risk for [[Vitamin deficiency|deficiency]].<ref name="Schorgg2021"/>

Dietary deficiency is rare. Classic clinical symptoms include [[rash]] and [[inflammation]] around the mouth and eyes, plus neurological effects that include drowsiness and [[peripheral neuropathy]] affecting [[sensory nerve|sensory]] and [[motor nerve]]s in the hands and feet. In addition to dietary shortfall, deficiency can be the result of [[antinutrient|anti-vitamin]] drugs. There are also rare genetic defects that can trigger vitamin B<sub>6</sub> deficiency-dependent [[epilepsy|epileptic seizures]] in infants. These are responsive to pyridoxal 5'-phosphate therapy.<ref name="Ghatge2021"/>

==Definition==
[[File:Pyridoxin.svg|thumb|120px|class=skin-invert-image|Pyridoxine (PN)]]
[[File:Pyridoxamin.svg|thumb|120px|class=skin-invert-image|Pyridoxamine (PM)]]
[[File:Pyridoxal2.svg|thumb|120px|class=skin-invert-image|Pyridoxal (PL)]]
Vitamin B<sub>6</sub> is a water-soluble [[vitamin]], one of the B vitamins. The vitamin actually comprises a group of six chemically related compounds, i.e., [[vitamer]]s, that all contain a [[pyridine]] ring as their core. These are [[pyridoxine]], [[pyridoxal]], [[pyridoxamine]], and their respective [[phosphorylation|phosphorylated]] derivatives [[pyridoxine 5'-phosphate]], [[Pyridoxal phosphate|pyridoxal 5'-phosphate]] and [[pyridoxamine 5'-phosphate]]. Pyridoxal 5'-phosphate has the highest [[biological activity]], but the others are convertible to that form.<ref name="Bachman2018">{{cite journal |vauthors=Bachmann T, Rychlik M |title=Synthesis of [13C₃]-B6 Vitamers Labelled at Three Consecutive Positions Starting from [13C₃]-Propionic Acid |journal=Molecules |volume=23 |issue=9 |pages= |date=August 2018 |pmid=30142892 |pmc=6225105 |doi=10.3390/molecules23092117 |url=|doi-access=free }}</ref> Vitamin B<sub>6</sub> serves as a [[Cofactor (biochemistry)|co-factor]] in more than 140 cellular reactions, mostly related to [[amino acid]] biosynthesis and catabolism, but is also involved in [[fatty acid]] biosynthesis and other physiological functions.<ref name=ODS/><ref name="lpi"/><ref name=PKIN2020B6 />

===Forms===
Because of its chemical stability, pyridoxine hydrochloride is the form most commonly given as vitamin B<sub>6</sub> dietary supplement. Absorbed pyridoxine (PN) is converted to pyridoxamine 5'-phosphate (PMP) by the enzyme [[pyridoxal kinase]], with PMP further converted to pyridoxal 5'-phosphate (PLP), the metabolically active form, by the enzymes [[pyridoxamine-phosphate transaminase]] or [[pyridoxine 5'-phosphate oxidase]], the latter of which also catalyzes the conversion of pyridoxine 5′-phosphate (PNP) to PLP.<ref name=PKIN2020B6 /><ref name="Bachman2018"/> Pyridoxine 5'-phosphate oxidase is dependent on [[flavin mononucleotide]] (FMN) as a cofactor produced from [[riboflavin]] (vitamin B<sub>2</sub>). For degradation, in a non-reversible reaction, PLP is [[Catabolism|catabolized]] to 4-pyridoxic acid, which is excreted in urine.<ref name=PKIN2020B6 />

==Synthesis==
===Biosynthesis===
{{Main|Pyridoxal phosphate #Biosynthesis}}

Two pathways for PLP are currently known: one requires deoxyxylulose 5-phosphate (DXP), while the other does not, hence they are known as DXP-dependent and DXP-independent. These pathways have been studied extensively in ''[[Escherichia coli]]''<ref>{{cite journal |vauthors=Tambasco-Studart M, Titiz O, Raschle T, Forster G, Amrhein N, Fitzpatrick TB |title=Vitamin B<sub>6</sub> biosynthesis in higher plants |journal=Proc Natl Acad Sci U S A |volume=102 |issue=38 |pages=13687–92 |date=September 2005 |pmid=16157873 |pmc=1224648 |doi=10.1073/pnas.0506228102 |bibcode=2005PNAS..10213687T |url=|doi-access=free }}</ref> and ''[[Bacillus subtilis]]'', respectively. Despite the disparity in the starting compounds and the different number of steps required, the two pathways possess many commonalities.<ref>{{cite journal | vauthors = Fitzpatrick TB, Amrhein N, Kappes B, Macheroux P, Tews I, Raschle T | title = Two independent routes of de novo vitamin B<sub>6</sub> biosynthesis: not that different after all | journal = The Biochemical Journal | volume = 407 | issue = 1 | pages = 1–13 | date = October 2007 | pmid = 17822383 | pmc =2267407 | doi = 10.1042/BJ20070765 | s2cid = 28231094 }}</ref> The DXP-dependent pathway:
[[File:Metabolic pathway- pyridoxal 5'-phosphate biosynthesis I v 2.0.svg|700px|center|class=skin-invert-image]]

===Commercial synthesis===
The starting material is either the amino acid [[alanine]], or [[propionic acid]] converted into alanine via [[halogenation]] and [[amination]]. Then, the procedure accomplishes the conversion of the amino acid into pyridoxine through the formation of an [[oxazole]] intermediate followed by a [[Diels–Alder reaction]], with the entire process referred to as the "oxazole method".<ref name="Bachman2018"/><ref name=Anie>{{cite journal |doi=10.1002/anie.201205886 |title=One Hundred Years of Vitamins-A Success Story of the Natural Sciences |year=2012 |last1=Eggersdorfer |first1=Manfred |last2=Laudert |first2=Dietmar |last3=Létinois |first3=Ulla |last4=McClymont |first4=Tom |last5=Medlock |first5=Jonathan |last6=Netscher |first6=Thomas |last7=Bonrath |first7=Werner |journal=Angewandte Chemie International Edition |volume=51 |issue=52 |pages=12973–12974 |pmid=23208776 }}</ref> The product used in dietary supplements and [[food fortification]] is [[pyridoxine hydrochloride]], the chemically stable [[hydrochloride]] salt of pyridoxine.<ref name="Wang2021"/> Pyridoxine is converted in the liver into the metabolically active coenzyme form pyridoxal 5'-phosphate. At present, while the industry mainly utilizes the oxazole method, there is research exploring means of using less toxic and dangerous reagents in the process.<ref name="Zou2013">{{cite journal |vauthors=Zou E, Shi X, Zhang G, Li Z, Jin C, Su W |title=Improved "Oxazole" Method for the Practical and Efficient Preparation of Pyridoxine Hydrochloride (Vitamin B<sub>6</sub>) |journal=Org Process Res Dev |volume=17 |issue=12 |pages=1498–502 |doi=10.1021/op4001687 |date=November 2013 |url=https://pubs.acs.org/doi/10.1021/op4001687 |url-access=subscription |access-date=August 16, 2021 |archive-date=May 22, 2022 |archive-url=https://web.archive.org/web/20220522062107/https://pubs.acs.org/doi/10.1021/op4001687 |url-status=live }}</ref> Fermentative bacterial biosynthesis methods are also being explored, but are not yet scaled up for commercial production.<ref name="Wang2021">{{cite journal |vauthors=Wang Y, Liu L, Jin Z, Zhang D |title=Microbial Cell Factories for Green Production of Vitamins |journal=Front Bioeng Biotechnol |volume=9 |issue= |pages=661562 |date=2021 |pmid=34222212 |pmc=8247775 |doi=10.3389/fbioe.2021.661562 |url=|doi-access=free }}</ref>

==Functions==
PLP is involved in many aspects of macronutrient metabolism, [[neurotransmitter]] synthesis, [[histamine]] synthesis, [[hemoglobin]] synthesis and function, and [[gene expression]]. PLP generally serves as a [[coenzyme]] (cofactor) for many reactions including [[decarboxylation]], [[transamination]], [[racemization]], [[elimination reaction|elimination]], [[single-displacement reaction|replacement]], and beta-group interconversion.<ref name=lpi/><ref name=PKIN2020B6 /><ref name="Combs">{{cite book|url=https://books.google.com/books?id=1CMHiWum0Y4C|title=The Vitamins: Fundamental Aspects in Nutrition and Health|vauthors=Combs GF|publisher=Elsevier Academic Press|year=2007|isbn=978-0-8121-0661-9|edition=3rd|location=San Diego|pages=320–324|lccn=2007026776|oclc=150255807|access-date=April 20, 2018|archive-date=December 31, 2023|archive-url=https://web.archive.org/web/20231231072054/https://books.google.com/books?id=1CMHiWum0Y4C|url-status=live}}</ref>

===Amino acid metabolism===
# [[Transaminase]]s break down amino acids with PLP as a cofactor. The proper activity of these enzymes is crucial for the process of moving [[amine]] groups from one amino acid to another. To function as a transaminase coenzyme, PLP bound to a [[lysine]] of the enzyme then binds to a free amino acid via formation of a [[Schiff's base]]. The process then dissociates the amine group from the amino acid, releasing a [[keto acid]], then transfers the amine group to a different keto acid to create a new amino acid.<ref name=PKIN2020B6 />
# [[Serine racemase]] which synthesizes the neuromodulator [[D-serine]] from its [[enantiomer]] is a PLP-dependent enzyme.
# PLP is a coenzyme needed for the proper function of the enzymes [[cystathionine synthase]] and [[cystathionase]]. These enzymes catalyze reactions in the catabolism of [[methionine]]. Part of this pathway (the reaction catalyzed by [[cystathionase]]) also produces [[cysteine]].
# [[Selenomethionine]] is the primary dietary form of [[selenium]]. PLP is needed as a cofactor for the enzymes that allow selenium to be used from the dietary form. PLP also plays a cofactor role in releasing selenium from selenohomocysteine to produce [[hydrogen selenide]], which can then be used to incorporate selenium into [[selenoprotein]]s.
# PLP is required for the conversion of [[tryptophan]] to [[Niacin (substance)|niacin]], so low vitamin B<sub>6</sub> status impairs this conversion.<ref name="Combs"/>

===Neurotransmitters===
PLP is a cofactor in the biosynthesis of five important [[neurotransmitters]]: [[serotonin]], [[dopamine]], [[epinephrine]], [[norepinephrine]], and [[gamma-aminobutyric acid]].<ref name="Parra2018"/>

===Glucose metabolism===
PLP is a required coenzyme of [[glycogen phosphorylase]], the enzyme necessary for [[glycogenolysis]]. [[Glycogen]] serves as a carbohydrate storage molecule, primarily found in muscle, liver and brain. Its breakdown frees up glucose for energy.<ref name="Parra2018"/> PLP also catalyzes transamination reactions that are essential for providing amino acids as a substrate for [[gluconeogenesis]], the biosynthesis of glucose.<ref name="Combs"/>

===Lipid metabolism===
PLP is an essential component of enzymes that facilitate the biosynthesis of [[sphingolipid]]s.<ref name="Combs"/> Particularly, the synthesis of [[ceramide]] requires PLP. In this reaction, serine is decarboxylated and combined with [[palmitoyl-CoA]] to form [[sphinganine]], which is combined with a fatty [[acyl-CoA]] to form dihydroceramide. This compound is then [[Dihydroceramide desaturase|further desaturated]] to form ceramide. In addition, the breakdown of sphingolipids is also dependent on vitamin B<sub>6</sub> because [[sphingosine-1-phosphate lyase]], the enzyme responsible for breaking down [[sphingosine-1-phosphate]], is also PLP-dependent.

===Hemoglobin synthesis and function===
PLP aids in the synthesis of [[hemoglobin]], by serving as a coenzyme for the enzyme [[aminolevulinic acid synthase]].<ref name="Parra2018"/> It also binds to two sites on hemoglobin to enhance the oxygen binding of hemoglobin.<ref name="Combs"/>

===Gene expression===
PLP has been implicated in increasing or decreasing the expression of certain [[gene]]s. Increased intracellular levels of the vitamin lead to a decrease in the [[transcription (genetics)|transcription]] of [[glucocorticoid]]s. Vitamin B<sub>6</sub> deficiency leads to the increased [[gene expression]] of [[albumin]] [[mRNA]]. Also, PLP influences expression of [[glycoprotein]] IIb by interacting with various [[transcription factor]]s; the result is inhibition of [[platelet]] aggregation.<ref name="Combs"/>

===In plants===
Plant synthesis of vitamin B<sub>6</sub> contributes to protection from sunlight. [[Ultraviolet#Subtypes|Ultraviolet-B radiation]] (UV-B) from sunlight stimulates plant growth, but in high amounts can increase production of tissue-damaging [[reactive oxygen species]] (ROS), i.e., [[oxidants]]. Using ''[[Arabidopsis thaliana]]'' (common name: thale cress), researchers demonstrated that UV-B exposure increased pyridoxine biosynthesis, but in a mutant variety, pyridoxine biosynthesis capacity was not [[Enzyme induction and inhibition|inducible]], and as a consequence, ROS levels, [[lipid peroxidation]], and cell proteins associated with tissue damage were all elevated.<ref name="Havaux2009">{{cite journal |vauthors=Havaux M, Ksas B, Szewczyk A, Rumeau D, Franck F, Caffarri S, Triantaphylidès C |title=Vitamin B6 deficient plants display increased sensitivity to high light and photo-oxidative stress |journal=BMC Plant Biol |volume=9 |issue= 1|pages=130 |date=November 2009 |pmid=19903353 |pmc=2777905 |doi=10.1186/1471-2229-9-130 |url= |doi-access=free |bibcode=2009BMCPB...9..130H }}</ref><ref>{{cite journal |vauthors=Ristilä M, Strid H, Eriksson LA, Strid A, Sävenstrand H |title=The role of the pyridoxine (vitamin B6) biosynthesis enzyme PDX1 in ultraviolet-B radiation responses in plants |journal=Plant Physiol Biochem |volume=49 |issue=3 |pages=284–92 |date=March 2011 |pmid=21288732 |doi=10.1016/j.plaphy.2011.01.003 |url=https://oru.diva-portal.org/smash/get/diva2:137027/FULLTEXT01 |access-date=March 20, 2024 |archive-date=January 6, 2024 |archive-url=https://web.archive.org/web/20240106034824/http://oru.diva-portal.org/smash/get/diva2:137027/FULLTEXT01 |url-status=live }}</ref><ref>{{cite journal |vauthors=Czégény G, Kőrösi L, Strid A, Hideg E |title=Multiple roles for Vitamin B<sub>6</sub> in plant acclimation to UV-B |journal=Scientific Reports |volume=9 |issue= 1|pages=1259 |date=February 2019 |pmid= 30718682|doi=10.1038/s41598-018-38053-w |url=|pmc=6361899 |bibcode=2019NatSR...9.1259C }}</ref> Biosynthesis of [[chlorophyll]] depends on aminolevulinic acid synthase, a PLP-dependent enzyme that uses [[succinyl-CoA]] and [[glycine]] to generate [[aminolevulinic acid]], a chlorophyll precursor.<ref name="Parra2018"/> In addition, plant mutants with severely limited capacity to synthesize vitamin B<sub>6</sub> have stunted root growth, because synthesis of [[plant hormone]]s such as [[auxin]] require the vitamin as an enzyme cofactor.<ref name="Parra2018"/>

==Medical uses==
{{see|Pyridoxine}}
[[Isoniazid]] is an [[antibiotic]] used for the treatment of [[tuberculosis]]. A common side effect is numbness in the hands and feet, also known as [[peripheral neuropathy]].<ref name=AHFS2016>{{cite web|title=Isoniazid|url=https://www.drugs.com/monograph/isoniazid.html|publisher=The American Society of Health-System Pharmacists|access-date=August 13, 2021|archive-date=December 20, 2016|archive-url=https://web.archive.org/web/20161220231039/https://www.drugs.com/monograph/isoniazid.html|url-status=live}}</ref> Co-treatment with vitamin B<sub>6</sub> alleviates the numbness.<ref name="Lheureux2005">{{cite journal |vauthors=Lheureux P, Penaloza A, Gris M |title=Pyridoxine in clinical toxicology: a review |journal=Eur J Emerg Med |volume=12 |issue=2 |pages=78–85 |date=April 2005 |pmid=15756083 |doi=10.1097/00063110-200504000-00007 |s2cid=39197646 |url=}}</ref>

Overconsumption of seeds from ''[[Ginkgo biloba]]'' can deplete vitamin B<sub>6</sub>, because the [[ginkgotoxin]] is an anti-vitamin (vitamin antagonist). Symptoms include vomiting and generalized convulsions. Ginkgo seed poisoning can be treated with vitamin B<sub>6</sub>.<ref>{{cite journal |vauthors=Mei N, Guo X, Ern Z, Kobayashi D, Wada K, Guo L |title=Review of ''Ginkgo biloba''-induced toxicity, from experimental studies to human case reports |journal=J Environ Sci Health C Environ Carcinog Ecotoxicol Rev |volume=35 |issue=1 |pages=1–28 |date=January 2017 |pmid=28055331 |pmc=6373469 |doi=10.1080/10590501.2016.1278298 |bibcode=2017JESHC..35....1M |url=}}</ref><ref>{{cite journal |vauthors=Kobayashi D |title=[Food Poisoning by Ginkgo Seeds through Vitamin B6 Depletion] |language=Japanese |journal=Yakugaku Zasshi |volume=139 |issue=1 |pages=1–6 |date=2019 |pmid=30606915 |doi=10.1248/yakushi.18-00136 |url=|doi-access=free }}</ref>

==Dietary recommendations==
From regulatory agency to regulatory agency there is a wide range between what is considered [[Tolerable upper intake level]]s (ULs). The [[European Food Safety Authority]] (EFSA) adult UL for vitamin B<sub>6</sub> is set at 12&nbsp;mg/day<ref name="EFSA2023"/> versus 100&nbsp;mg/day for the United States.<ref name="DRItext"/> 

The US [[National Academy of Medicine]] updated [[Dietary Reference Intake]]s for many vitamins in 1998. Recommended Dietary Allowances (RDAs), expressed as milligrams per day, increase with age from 1.2 to 1.5&nbsp;mg/day for women and from 1.3 to 1.7&nbsp;mg/day for men. The RDA for pregnancy is 1.9&nbsp;mg/day, for [[lactation]], 2.0&nbsp;mg/day. For children ages 1–13 years the RDA increases with age from 0.5 to 1.0&nbsp;mg/day. As for safety, ULs for vitamins and minerals are identified when evidence is sufficient. In the case of vitamin B<sub>6</sub> the US-established adult UL was set at 100&nbsp;mg/day.<ref name="DRItext">{{cite book|chapter-url=https://www.nap.edu/read/6015/chapter/9#150|title=Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline|last1=Institute of Medicine|author-link=Institute of Medicine|publisher=The National Academies Press|year=1998|isbn=978-0-309-06554-2|location=Washington, DC|pages=150–195|chapter=Vitamin B<sub>6</sub>|doi=10.17226/6015|pmid=23193625|lccn=00028380|oclc=475527045|access-date=April 20, 2018|archive-date=March 6, 2022|archive-url=https://web.archive.org/web/20220306133707/https://www.nap.edu/read/6015/chapter/9#150|url-status=live}}</ref>

The EFSA refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA. For women and men ages 15 and older the PRI is set at 1.6 and 1.7&nbsp;mg/day, respectively; for pregnancy 1.8&nbsp;mg/day, for lactation 1.7&nbsp;mg/day. For children ages 1–14 years the PRIs increase with age from 0.6 to 1.4&nbsp;mg/day.<ref>{{cite web|url=https://www.efsa.europa.eu/sites/default/files/assets/DRV_Summary_tables_jan_17.pdf |title=Overview on Dietary Reference Values for the EU population as derived by the EFSA Panel on Dietetic Products, Nutrition and Allergies | year=2017|archive-url=https://web.archive.org/web/20170828082247/https://www.efsa.europa.eu/sites/default/files/assets/DRV_Summary_tables_jan_17.pdf|archive-date=August 28, 2017|url-status=live}}</ref> The EFSA also reviewed the safety question and in 2023 set an upper limit for vitamin B<sub>6</sub> of 12&nbsp;mg/day for adults, with lower amounts ranging from 2.2 to 10.7 mg/day for infants and children, depending on age.<ref name="EFSA2023">{{cite journal |vauthors=Turck D, Bohn T, Castenmiller J, de Henauw S, Hirsch-Ernst KI, Knutsen HK, Maciuk A, Mangelsdorf I, McArdle HJ, Pelaez C, Pentieva K, Siani A, Thies F, Tsabouri S, Vinceti M, Fairweather-Tait S, Vrolijk M, Fabiani L, Titz A, Naska A |display-authors=5 |title=Scientific opinion on the tolerable upper intake level for vitamin B6 |journal=EFSA J |volume=21 |issue=5 |pages=e08006 |date=May 2023 |pmid=37207271 |pmc=10189633 |doi=10.2903/j.efsa.2023.8006 |url=}}</ref> This replaced the adult UL set in 2008 at 25&nbsp;mg/day.<ref name="EFSA2008">{{cite journal |publisher=Scientific Panel on Food Additives, Flavorings, Processing Aids and Materials in Contact with Food |date=2008 |title=Opinion on Pyridoxal 5′-phosphate as a source for vitamin B<sub>6</sub> added for nutritional purposes in food supplements |url=https://www.efsa.europa.eu/en/efsajournal/pub/760 |journal=The EFSA Journal |volume=760 |issue=7 |page=760 |doi=10.2903/j.efsa.2008.760 |pmid=37213840 |doi-access=free |pmc=10193624 |author1=European Food Safety Authority (EFSA) |access-date=September 22, 2019 |archive-date=October 24, 2020 |archive-url=https://web.archive.org/web/20201024062140/https://www.efsa.europa.eu/en/efsajournal/pub/760 |url-status=live }}</ref>

The Japanese [[Ministry of Health, Labour and Welfare]] updated its vitamin and mineral recommendations in 2015. The adult RDAs are at 1.2&nbsp;mg/day for women 1.4&nbsp;mg/day for men. The RDA for pregnancy is 1.4&nbsp;mg/day, for lactation is 1.5&nbsp;mg/day. For children ages 1–17 years the RDA increases with age from 0.5 to 1.5&nbsp;mg/day. The adult UL was set at 40–45&nbsp;mg/day for women and 50–60&nbsp;mg/day for men, with the lower values in those ranges for adults over 70 years of age.<ref name="JapanDRI2015">{{cite web |url=https://www.mhlw.go.jp/file/06-Seisakujouhou-10900000-Kenkoukyoku/Overview.pdf |title=Overview of Dietary Reference Intakes for Japanese |website=Ministry of Health, Labour and Welfare (Japan) |date=2015 |access-date=August 19, 2021 |archive-date=October 21, 2022 |archive-url=https://web.archive.org/web/20221021004240/https://www.mhlw.go.jp/file/06-Seisakujouhou-10900000-Kenkoukyoku/Overview.pdf |url-status=live }}</ref>

===Safety===
{{Main|Megavitamin-B6 syndrome}}
Adverse effects have been documented from vitamin B<sub>6</sub> dietary supplements, but never from food sources. Even though it is a water-soluble vitamin and is excreted in the urine, doses of pyridoxine in excess of the dietary upper limit (UL) over long periods cause painful and ultimately irreversible neurological problems.<ref name="DRItext" /> The primary symptoms are pain and numbness of the extremities. In severe cases, motor neuropathy may occur with "slowing of motor conduction velocities, prolonged [[F wave]] latencies, and prolonged sensory latencies in both lower extremities", causing difficulty in walking. Sensory [[neuropathy]] typically develops at doses of pyridoxine in excess of 1,000&nbsp;mg per day, but adverse effects can occur with much less, so intakes over 200&nbsp;mg/day are not considered safe.<ref name="DRItext" /> Trials with amounts equal to or less than 200&nbsp;mg/day established that as a "[[No-observed-adverse-effect level]]", meaning the highest amount at which no adverse effects were observed. This was divided by two to allow for people who might be extra sensitive to the vitamin, referred to as an "uncertainty factor", resulting in the aforementioned adult UL of 100&nbsp;mg/day set for the United States.<ref name="DRItext" /> As noted above, in 2023 the European Food Safety Commission set an adult UL at 12&nbsp;mg/day.<ref name="EFSA2023"/> While Australia has set an upper limit of 50&nbsp;mg/day, the [[Therapeutic Goods Administration]] requires a label warning about peripheral neuropathy if the daily dose is predicted to exceed 10&nbsp;mg/day.<ref name="NHMRC2019">{{cite web |title=Vitamin B<sub>6</sub> |website=Nutrient Reference Values for Australia and New Zealand |publisher=National Health and Medication Research Council (NHMRC) |url=https://www.nrv.gov.au/nutrients/vitamin-b6 |access-date=2019-12-02 |archive-date=2019-03-04 |archive-url=https://web.archive.org/web/20190304153020/https://www.nrv.gov.au/nutrients/vitamin-b6|date=2014-03-17 }}</ref><ref>{{cite web |title=Peripheral neuropathy with supplementary vitamin B6 (pyridoxine) |url=https://www.tga.gov.au/news/safety-updates/peripheral-neuropathy-supplementary-vitamin-b6-pyridoxine |website=[[Therapeutic Goods Administration]] |publisher=[[Australian Government]] |access-date=5 January 2025}}</ref>

===Labeling===
For US food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value. For vitamin B<sub>6</sub> labeling purposes 100% of the Daily Value was 2.0&nbsp;mg, but as of May 27, 2016, it was revised to 1.7&nbsp;mg to bring it into agreement with the adult RDA.<ref name="FedReg">{{cite web|url=https://www.gpo.gov/fdsys/pkg/FR-2016-05-27/pdf/2016-11867.pdf|title=Federal Register May 27, 2016 Food Labeling: Revision of the Nutrition and Supplement Facts Labels |archive-url=https://web.archive.org/web/20170922104400/https://www.gpo.gov/fdsys/pkg/FR-2016-05-27/pdf/2016-11867.pdf|archive-date=September 22, 2017|url-status=live}}</ref><ref>{{cite web | title=Daily Value Reference of the Dietary Supplement Label Database (DSLD) | website=Dietary Supplement Label Database (DSLD) | url=https://www.dsld.nlm.nih.gov/dsld/dailyvalue.jsp | access-date=May 16, 2020 | archive-date=April 7, 2020 | archive-url=https://web.archive.org/web/20200407073956/https://dsld.nlm.nih.gov/dsld/dailyvalue.jsp | url-status=dead }}</ref> A table of the old and new adult daily values is provided at [[Reference Daily Intake]].

==Sources==
Bacteria residing in the [[large intestine]] are known to synthesize B-vitamins, including B<sub>6</sub>, but the amounts are not sufficient to meet host requirements, in part because the vitamins are competitively taken up by non-synthesizing bacteria.<ref>{{cite journal |vauthors=Mayengbam S, Chleilat F, Reimer RA |title=Dietary Vitamin B6 Deficiency Impairs Gut Microbiota and Host and Microbial Metabolites in Rats |journal=Biomedicines |volume=8 |issue=11 |date=November 2020 |page=469 |pmid=33147768 |pmc=7693528 |doi=10.3390/biomedicines8110469 |url=|doi-access=free }}</ref>

Vitamin B<sub>6</sub> is found in a wide variety of foods. In general, meat, fish and fowl are good sources, but dairy foods and eggs are not (table).<ref name="FoodsHigh">{{cite news |url=https://www.nutritionadvance.com/foods-high-in-vitamin-b6/ |title=30 Foods High In Vitamin B6 |last=Joseph |first=Michael |date=January 10, 2021 |website=Nutrition Advance |access-date=August 17, 2021 |quote=All nutritional values within this article have been sourced from the USDA's FoodData Central Database. |archive-date=July 19, 2022 |archive-url=https://web.archive.org/web/20220719165534/https://www.nutritionadvance.com/foods-high-in-vitamin-b6/ |url-status=live }}</ref><ref name="FoodsDataCentral">{{cite web |url=https://fdc.nal.usda.gov/index.html |title=USDA Food Data Central. Standard Reference, Legacy Foods |date=April 2018 |website=USDA Food Data Central |access-date=August 18, 2021 |archive-date=December 3, 2019 |archive-url=https://web.archive.org/web/20191203185131/https://fdc.nal.usda.gov/index.html |url-status=live }}</ref> Crustaceans and mollusks contain about 0.1&nbsp;mg/100 grams. Fruit (apples, oranges, pears) contain less than 0.1&nbsp;mg/100g.<ref name="FoodsDataCentral"/>

[[Bioavailability]] from a mixed diet (containing animal- and plant-sourced foods) is estimated at being 75% – higher for PLP from meat, fish and fowl, lower from plants, as those are mostly in the form of pyridoxine [[glucoside]], which has approximately half the bioavailability of animal-sourced B<sub>6</sub> because removal of the glucoside by intestinal cells is not 100% efficient.<ref name="DRItext" /> Given lower amounts and lower bioavailability of the vitamin from plants there was a concern that a vegetarian or vegan diet could cause a vitamin deficiency state. However, the results from a population-based survey conducted in the U.S. demonstrated that despite a lower vitamin intake, serum PLP was not significantly different between meat-eaters and vegetarians, suggesting that a vegetarian diet does not pose a risk for vitamin B<sub>6</sub> deficiency.<ref name="Schorgg2021">{{cite journal |vauthors=Schorgg P, Bärnighausen T, Rohrmann S, Cassidy A, Karavasiloglou N, Kühn T |title=Vitamin B6 Status among Vegetarians: Findings from a Population-Based Survey |journal=Nutrients |volume=13 |issue=5 |date=May 2021 |page=1627 |pmid=34066199 |pmc=8150266 |doi=10.3390/nu13051627 |url=|doi-access=free }}</ref>

Cooking, storage, and processing losses vary, and in some foods may be more than 50% depending on the form of vitamin present in the food.<ref name=PKIN2020B6>{{cite book |vauthors=Da Silva VR, Gregory III JF |title = Present Knowledge in Nutrition, Eleventh Edition |chapter = Vitamin B6 |editor=BP Marriott |editor2=DF Birt |editor3=VA Stallings|editor4=AA Yates |publisher = Academic Press (Elsevier) |year=2020 |location = London, United Kingdom |pages = 225–38 |isbn=978-0-323-66162-1}}</ref> Plant foods lose less during processing, as they contain pyridoxine, which is more stable than the pyridoxal or pyridoxamine forms found in animal-sourced foods. For example, milk can lose 30–70% of its vitamin B<sub>6</sub> content when [[dried milk|dried]].<ref name="Combs"/> The vitamin is found in the [[Cereal germ|germ]] and [[aleurone]] layer of grains, so there is more in grains from which these layers have not been removed, for example more in [[whole wheat bread]] than in [[White bread|white wheat bread]], and more in [[brown rice]] than in [[white rice]].<ref name="FoodsDataCentral"/>

Most values shown in the table are rounded to nearest tenth of a milligram:

<div style="float:left; padding: 1em;">
{|class="wikitable"
|-
!Source<ref name="FoodsHigh"/><ref name="FoodsDataCentral"/>

!Amount<br /> (mg per 100 grams)
|-
|[[Whey]] protein concentrate || 1.2
|-
|[[Beef]] liver, pan-fried || 1.0
|-
|[[Tuna]], skipjack, cooked || 1.0
|-
|[[Beef]] steak, grilled || 0.9
|-
|[[Salmon]], Atlantic, cooked || 0.9
|-
|[[Chicken]] breast, grilled || 0.7
|-
|[[Pork]] chop, cooked || 0.6
|-
|[[Turkey (bird)|Turkey]], ground, cooked || 0.6
|}
</div>
<div style="float:left; padding: 1em;">
{|class="wikitable"
|-
!Source<ref name="FoodsHigh"/><ref name="FoodsDataCentral"/>
!Amount<br /> (mg per 100 grams)
|-
|[[Pistachio]]
|1.7
|-
|[[Mushroom]], [[Shiitake]], raw || 0.3
|-
|[[Potato]], baked, with skin || 0.3
|-
|[[Sweet potato]] baked || 0.3
|-
|[[Bell pepper]], red || 0.3
|-
|[[Peanut]]s || 0.3
|-
|[[Avocado]] || 0.25
|-
|[[Spinach]] || 0.2
|-
|[[Tofu]], firm || 0.1
|}
</div>
<div style="float:left; padding: 1em;">
{|class="wikitable"
|-
!Source<ref name="FoodsDataCentral"/>
!Amount<br /> (mg per 100 grams)
|-
|[[Grits|Corn grits]] || 0.1
|-
|[[Milk]], whole || 0.1 (one cup)
|-
|[[Yogurt]] || 0.1 (one cup)
|-
|[[Almonds]] || 0.1
|-
|[[Bread]], whole wheat/white || 0.2/0.1
|-
|[[Rice]], cooked, brown/white || 0.15/0.02
|-
|[[Bean]]s, baked || 0.1
|-
|[[Bean]]s, green || 0.1
|-
|[[Egg as food|Chicken egg]] || 0.1
|}
</div>{{Clear}}

===Fortification===
As of 2024, eighteen countries require food fortification of wheat flour, [[maize]] flour or rice with vitamin B<sub>6</sub> as pyridoxine hydrochloride. Most of these are in southeast Africa or Central America. The amounts stipulated range from 3.0 to 6.5&nbsp;mg/kg. An additional six countries, including India, have a voluntary fortification program. India stipulates 2.0&nbsp;mg/kg.<ref name="Map">{{cite web |url=https://fortificationdata.org/map-number-of-nutrients/ |title=Map: Count of Nutrients In Fortification Standards |website=Global Fortification Data Exchange |date=November 29, 2024 |access-date=November 29, 2024 }}</ref>

===Dietary supplements===
In the US, multi-vitamin/mineral products typically contain 2 to 4&nbsp;mg of vitamin B<sub>6</sub> per daily serving as pyridoxine hydrochloride. However, many US dietary supplement companies also market a B<sub>6</sub>-only dietary supplement with 100&nbsp;mg per daily serving.<ref name=ODS/> While the [[US National Academy of Medicine]] set an adult safety UL at 100&nbsp;mg/day in 1998,<ref name=ODS/><ref name="DRItext"/> in 2023 the European Food Safety Authority set its UL at 12&nbsp;mg/day.<ref name="EFSA2023"/>

====Health claims====
The Japanese Ministry of Health, Labor, and Welfare (MHLW) set up the 'Foods for Specified Health Uses' ({{Nihongo2|特定保健用食品}}; FOSHU) regulatory system in 1991 to individually approve the statements made on food labels concerning the effects of foods on the human body. The regulatory range of FOSHU was later broadened to allow for the certification of capsules and tablets. In 2001, MHLW enacted a new regulatory system, 'Foods with Health Claims' ({{Nihongo2|保健機能食品}}; FHC), which consists of the existing FOSHU system and the newly established 'Foods with Nutrient Function Claims' ({{Nihongo2|栄養機能表示食品}}; FNFC), under which claims were approved for any product containing a specified amount per [[Serving size|serving]] of 12 vitamins, including vitamin B<sub>6</sub>, and two minerals.<ref>{{cite journal |vauthors=Shimizu T |title=Health claims on functional foods: the Japanese regulations and an international comparison |journal=Nutr Res Rev |volume=16 |issue=2 |pages=241–52 |date=December 2003 |pmid=19087392 |doi=10.1079/NRR200363 |url=|doi-access=free }}</ref><ref>{{cite journal|vauthors=Harada K|date=2016|title=食品中の機能性成分解析|trans-title=Analysis of Functional Ingredients in Foods|url=https://www.jstage.jst.go.jp/article/bunsekikagaku/65/6/65_309/_article/-char/ja/|journal=Bunseki Kagaku|language=ja|publisher=The Japan Society for Analytical Chemistry|volume=65|issue=6|pages=309–319|doi=10.2116/bunsekikagaku.65.309|issn=0525-1931|doi-access=free|access-date=September 23, 2021|archive-date=February 10, 2023|archive-url=https://web.archive.org/web/20230210210435/https://www.jstage.jst.go.jp/article/bunsekikagaku/65/6/65_309/_article/-char/ja/|url-status=live}}</ref> To make a health claim based on a food's vitamin B<sub>6</sub> content, the amount per serving must be in the range of 0.3–25&nbsp;mg. The allowed claim is: "Vitamin B<sub>6</sub> is a nutrient that helps produce energy from protein and helps maintain healthy skin and [[mucous membranes]]."<ref>{{cite journal|vauthors=Shimizu T|date=2001|title=新しい保健機能性食晶制度の概要|trans-title=Newly Established Regulation: Foods with Health Claims|url=http://www.ilsijapan.org/ILSIJapan/BOOK/Ilsi/PDF/ILSI066.pdf|journal=Journal of the [[International Life Sciences Institute]] of Japan|language=ja|volume=66|pages=9–15|quote=|access-date=September 23, 2021|archive-date=February 24, 2023|archive-url=https://web.archive.org/web/20230224004852/http://www.ilsijapan.org/ILSIJapan/BOOK/Ilsi/PDF/ILSI066.pdf|url-status=live}}</ref><ref>{{cite web|title=(問14) 栄養機能食品の規格基準及び表示の基準とは、どのようなものか|trans-title=Question 14—What are the standards and labeling criteria for Foods with Nutrient Function Claims?|url=https://www.mhlw.go.jp/topics/2002/03/tp0313-2c.html|access-date=September 23, 2021|website=[[Ministry of Health, Labor, and Welfare]]|language=ja|quote=ビタミンB<sub>6</sub>は、たんぱく質からのエネルギー産生と皮膚や粘膜の健康維持を助ける栄養素です.|archive-date=September 23, 2021|archive-url=https://web.archive.org/web/20210923220429/https://www.mhlw.go.jp/topics/2002/03/tp0313-2c.html|url-status=dead}}</ref>

In 2010, the European Food Safety Authority (EFSA) published a review of proposed health claims for vitamin B<sub>6</sub>, disallowing claims for bone, teeth, hair skin and nails, and allowing claims that the vitamin provided for normal [[homocysteine]] metabolism, normal energy-yielding metabolism, normal psychological function, reduced tiredness and fatigue, and provided for normal cysteine synthesis.<ref>{{cite journal |vauthors= |title=Scientific Opinion on the substantiation of health claims related to vitamin B6 |journal=EFSA Journal |volume=8 |issue=10 |pages=1759 |date=2010 |pmid= |doi=10.2903/j.efsa.2010.1759 |doi-access= }}</ref>

The US [[Food and Drug Administration]] (FDA) has several processes for permitting health claims on food and dietary supplement labels.<ref name="HealthClaims">{{cite web |url=https://www.fda.gov/food/food-labeling-nutrition/label-claims-conventional-foods-and-dietary-supplements |title=Label Claims for Conventional Foods and Dietary Supplements |date=June 19, 2018 |website=U.S. Food and Drug Administration |access-date=August 17, 2021 |archive-date=August 17, 2021 |archive-url=https://web.archive.org/web/20210817214246/https://www.fda.gov/food/food-labeling-nutrition/label-claims-conventional-foods-and-dietary-supplements |url-status=live }}</ref> There are no FDA-approved Health Claims or Qualified Health Claims for vitamin B<sub>6</sub>. Structure/Function Claims can be made without FDA review or approval as long as there is some credible supporting science.<ref name="HealthClaims"/> Examples for this vitamin are "Helps support nervous system function" and "Supports healthy homocysteine metabolism."

==Absorption, metabolism and excretion==
Vitamin B<sub>6</sub> is absorbed in the [[jejunum]] of the small intestine by [[passive diffusion]].<ref name=ODS/><ref name="DRItext"/> Even extremely large amounts are well absorbed. Absorption of the phosphate forms involves their dephosphorylation catalyzed by the enzyme [[alkaline phosphatase]].<ref name="Combs"/> Most of the vitamin is taken up by the liver. There, the dephosphorylated vitamins are converted to the phosphorylated PLP, PNP and PMP, with the two latter converted to PLP. In the liver, PLP is bound to proteins, primarily albumin. The PLP-albumin complex is what is released by the liver to circulate in plasma.<ref name="DRItext"/> Protein-binding capacity is the limiting factor for vitamin storage. Total body stores, the majority in muscle, with a lesser amount in liver, have been estimated to be in the range of 61 to 167&nbsp;mg.<ref name="DRItext"/>

Enzymatic processes utilize PLP as a phosphate-donating cofactor. PLP is restored via a [[salvage pathway]] that requires three key enzymes, [[pyridoxal kinase]], [[pyridoxine 5'-phosphate oxidase]], and [[phosphatase]]s.<ref name="Parra2018">{{cite journal |vauthors=Parra M, Stahl S, Hellmann H |title=Vitamin B<sub>6</sub> and Its Role in Cell Metabolism and Physiology |journal=Cells |volume=7 |issue=7 |date=July 2018 |page=84 |pmid=30037155 |pmc=6071262 |doi=10.3390/cells7070084 |url=|doi-access=free }}</ref><ref name="Ghatge2021"/> Inborn errors in the salvage enzymes are known to cause inadequate levels of PLP in the cell, particularly in neuronal cells. The resulting PLP deficiency is known to cause or implicated in several pathologies, most notably infant epileptic seizures.<ref name="Ghatge2021"/>

The half-life of vitamin B<sub>6</sub> varies according to different sources: one source suggests that the half-life of ''pyridoxine'' is up to 20 days,<ref name="days20">{{cite book|doi=10.1007/978-3-319-20790-2_174-1|quote=The half-life of pyridoxine is up to 20 days. |chapter=Pyridoxine |title=Critical Care Toxicology |date=2016 |last1=Kennedy |first1=Ashleigh |last2=Schaeffer |first2=Tammi |pages=1–4 |isbn=978-3-319-20790-2 }}</ref> while another source indicates half-life of ''vitamin B<sub>6</sub>'' is in range of 25 to 33 days.<ref name="VKM2017">{{cite book |title=Assessment of vitamin B<sub>6</sub> intake in relation to tolerable upper intake levels. Opinion of the Panel on Nutrition, Dietetic Products, Novel Food and Allergy of the Norwegian Scientific Committee for Food Safety |isbn=978-82-8259-260-4 |location=Oslo, Norway |url=https://vkm.no/download/18.645b840415d03a2fe8f2653d/1499330353450/087ba2170f.pdf |access-date=7 December 2019 |archive-url=https://web.archive.org/web/20191117011203/https://vkm.no/download/18.645b840415d03a2fe8f2653d/1499330353450/087ba2170f.pdf |archive-date=17 November 2019 | quote=Eighty to ninety percent of vitamin B6 in the body is found in muscles and estimated body stores in adults amount to about 170 mg with a half-life of 25-33 days.}}</ref> After considering the different sources, it can be concluded that the half-life of vitamin B<sub>6</sub> is typically measured in several weeks.<ref name="days20"/><ref name="VKM2017"/>

The end-product of vitamin B<sub>6</sub> catabolism is 4-pyridoxic acid, which makes up about half of the B<sub>6</sub> compounds in urine. 4-Pyridoxic acid is formed by the action of [[aldehyde oxidase]] in the liver. Amounts excreted increase within 1–2 weeks with vitamin supplementation and decrease as rapidly after supplementation ceases.<ref name="DRItext"/><ref name=Ueland2015 /> Other vitamin forms excreted in the urine include pyridoxal, pyridoxamine and pyridoxine, and their phosphates. When large doses of pyridoxine are given orally, the proportion of these other forms increases. A small amount of vitamin B<sub>6</sub> is also excreted in the feces. This may be a combination of unabsorbed vitamin and what was synthesized by large intestine microbiota.<ref name="DRItext"/>

==Deficiency==
===Signs and symptoms===
The classic clinical syndrome for vitamin B<sub>6</sub> deficiency is a [[seborrheic dermatitis]]-like eruption, [[atrophic glossitis]] with [[mouth ulcer|ulceration]], [[angular cheilitis]], [[conjunctivitis]], [[intertrigo]], abnormal [[electroencephalograms]], [[microcytic anemia]] (due to impaired [[heme]] synthesis), and neurological symptoms of [[somnolence]], confusion, depression, and [[neuropathy]] (due to impaired [[sphingosine]] synthesis).<ref name=ODS/>

In infants, a deficiency in vitamin B<sub>6</sub> can lead to irritability, abnormally acute hearing, and convulsive seizures.<ref name=ODS/>

Less severe cases present with metabolic disease associated with insufficient activity of the [[coenzyme]] [[Pyridoxal phosphate|pyridoxal 5' phosphate]] (PLP).<ref name=ODS/> The most prominent of the lesions is due to impaired [[tryptophan]]–[[Niacin (substance)|niacin]] conversion. This can be detected based on urinary excretion of [[xanthurenic acid]] after an oral tryptophan load. Vitamin B<sub>6</sub> deficiency can also result in impaired [[transsulfuration]] of [[methionine]] to [[cysteine]]. The PLP-dependent transaminases and glycogen phosphorylase provide the vitamin with its role in [[gluconeogenesis]], so deprivation of vitamin B<sub>6</sub> results in impaired [[glucose tolerance]].<ref name=ODS/><ref name="Combs"/>

===Diagnosis===
The assessment of vitamin B<sub>6</sub> status is essential, as the clinical signs and symptoms in less severe cases are not specific.<ref>{{cite book|chapter-url=https://books.google.com/books?id=lBlu7UKI3aQC|title=Principles of Nutritional Assessment|vauthors=Gibson RS|publisher=Oxford University Press|year=2005|isbn=978-0-19-517169-3|edition=2nd|location=New York|pages=575–594|chapter=Assessment of vitamin B<sub>6</sub> status|lccn=2004054778|oclc=884490740|access-date=April 20, 2018|archive-date=December 31, 2023|archive-url=https://web.archive.org/web/20231231072056/https://books.google.com/books?id=lBlu7UKI3aQC|url-status=live}}</ref> The three biochemical tests most widely used are plasma PLP concentrations, the activation coefficient for the erythrocyte enzyme aspartate aminotransferase, and the urinary excretion of vitamin B<sub>6</sub> degradation products, specifically urinary PA. Of these, plasma PLP is probably the best single measure, because it reflects tissue stores. Plasma PLP of less than 10&nbsp;nmol/L is indicative of vitamin B<sub>6</sub> deficiency.<ref name=Ueland2015>{{cite journal |vauthors=Ueland PM, Ulvik A, Rios-Avila L, Midttun Ø, Gregory JF |title=Direct and Functional Biomarkers of Vitamin B6 Status |journal=Annu Rev Nutr |volume=35 |issue= |pages=33–70 |date=2015 |pmid=25974692 |pmc=5988249 |doi=10.1146/annurev-nutr-071714-034330 |url=}}</ref> A PLP concentration greater than 20&nbsp;nmol/L has been chosen as a level of adequacy for establishing Estimated Average Requirements and Recommended Daily Allowances in the USA.<ref name="DRItext" /> Urinary PA is also an indicator of vitamin B<sub>6</sub> deficiency; levels of less than 3.0&nbsp;mmol/day is suggestive of vitamin B<sub>6</sub> deficiency.<ref name=Ueland2015 /> Other methods of measurement, including [[Ultraviolet–visible spectroscopy|UV spectrometric]], [[Fluorescence spectroscopy|spectrofluorimetric]], [[Mass spectrometry|mass spectrometric]], [[thin-layer chromatography|thin-layer]] and [[High-performance liquid chromatography|high-performance liquid chromatographic]], [[Electrophoresis|electrophoretic]], [[electrochemistry|electrochemical]], and enzymatic, have been developed.<ref name=Ueland2015 /><ref>{{cite journal |vauthors=Ahmad I, Mirza T, Qadeer K, Nazim U, Vaid FH |title=Vitamin B6: deficiency diseases and methods of analysis |journal=Pak J Pharm Sci |volume=26 |issue=5 |pages=1057–69 |date=September 2013 |pmid=24035968 |doi= |url=}}</ref>

The classic clinical symptoms for vitamin B<sub>6</sub> deficiency are rare, even in developing countries. A handful of cases were seen between 1952 and 1953, particularly in the United States, having occurred in a small percentage of infants who were fed a formula lacking in pyridoxine.<ref name="TCN">{{cite book |url=https://books.google.com/books?id=og-0AAAAIAAJ |title=Textbook of Child Neurology |last=Menkes |first=John H. |publisher=Henry Kimpton Publishers |year=1980 |isbn=978-0-8121-0661-9 |edition=2nd |location=Philadelphia |page=486 |lccn=79010975 |oclc=925196268 |access-date=April 20, 2018 |archive-date=December 31, 2023 |archive-url=https://web.archive.org/web/20231231072058/https://books.google.com/books?id=og-0AAAAIAAJ |url-status=live }}</ref>

===Causes===
A deficiency of vitamin B<sub>6</sub> alone is relatively uncommon and often occurs in association with other vitamins of the B complex. Evidence exists for decreased levels of vitamin B<sub>6</sub> in women with [[type 1 diabetes]] and in patients with [[systemic inflammation]], liver disease, [[rheumatoid arthritis]], and those infected with [[HIV]].<ref>{{cite journal | vauthors = Massé PG, Boudreau J, Tranchant CC, Ouellette R, Ericson KL | title = Type 1 diabetes impairs vitamin B(6) metabolism at an early stage of women's adulthood | journal = Applied Physiology, Nutrition, and Metabolism| volume = 37 | issue = 1 | pages = 167–75 | date = February 2012 | pmid = 22288928 | doi = 10.1139/h11-146 }}</ref><ref>{{cite journal | vauthors = Ulvik A, Midttun Ø, Pedersen ER, Eussen SJ, Nygård O, Ueland PM | title = Evidence for increased catabolism of vitamin B-6 during systemic inflammation | journal = The American Journal of Clinical Nutrition | volume = 100 | issue = 1 | pages = 250–5 | date = July 2014 | pmid = 24808485 | doi = 10.3945/ajcn.114.083196 | doi-access = free }}</ref> Use of [[oral contraceptive]]s and treatment with certain [[anticonvulsant]]s, [[isoniazid]], [[cycloserine]], [[penicillamine]], and [[hydrocortisone]] negatively impact vitamin B<sub>6</sub> status.<ref name=ODS/><ref>{{cite journal | vauthors = Wilson SM, Bivins BN, Russell KA, Bailey LB | title = Oral contraceptive use: impact on folate, vitamin B<sub>6</sub>, and vitamin B<sub>12</sub> status | journal = Nutrition Reviews | volume = 69 | issue = 10 | pages = 572–83 | date = October 2011 | pmid = 21967158 | doi = 10.1111/j.1753-4887.2011.00419.x | doi-access = free }}</ref><ref>{{cite journal | vauthors = Schwaninger M, Ringleb P, Winter R, Kohl B, Fiehn W, Rieser PA, Walter-Sack I | title = Elevated plasma concentrations of homocysteine in antiepileptic drug treatment | journal = Epilepsia | volume = 40 | issue = 3 | pages = 345–50 | date = March 1999 | pmid = 10080517 | doi = 10.1111/j.1528-1157.1999.tb00716.x | doi-access = free }}</ref> [[Hemodialysis]] reduces vitamin B<sub>6</sub> plasma levels.<ref>{{cite journal | vauthors = Corken M, Porter J | title = Is vitamin B(6) deficiency an under-recognized risk in patients receiving haemodialysis? A systematic review: 2000-2010 | journal = Nephrology | volume = 16 | issue = 7 | pages = 619–25 | date = September 2011 | pmid = 21609363 | doi = 10.1111/j.1440-1797.2011.01479.x | s2cid = 22894817 | doi-access = free }}</ref> Overconsumption of ''[[Ginkgo biloba]]'' seeds can also deplete vitamin B<sub>6</sub>.<ref name="Kobayashi2019">{{cite journal |last1=Kobayashi |first1=Daisuke |title=Food poisoning by Ginkgo seeds through vitamin B<sub>6</sub> depletion (article in Japanese) |journal=Yakugaku Zasshi |volume=139 |issue=1 |year=2019 |pages=1–6 |issn=0031-6903 |doi=10.1248/yakushi.18-00136 |pmid=30606915 |doi-access=free}}</ref><ref name="WadaIshigaki1985">{{cite journal |last1=Wada |first1=Keiji |last2=Ishigaki |first2=Seikou |last3=Ueda |first3=Kaori |last4=Sakata |first4=Masakatsu |last5=Haga |first5=Masanobu |title=An antivitamin B6, 4'-methoxypyridoxine, from the seed of Ginkgo biloba L. |journal=Chemical & Pharmaceutical Bulletin |volume=33 |issue=8 |year=1985 |pages=3555–3557 |issn=0009-2363 |doi=10.1248/cpb.33.3555 |pmid=4085085 |doi-access=free}}</ref>

====Genetic defects====
Genetically confirmed diagnoses of diseases affecting vitamin B<sub>6</sub> metabolism ([[ALDH7A1]] deficiency, [[PNPO|pyridoxine-5'-phosphate oxidase deficiency]], [[Pyridoxal phosphate|PLP binding protein deficiency]], [[hyperprolinaemia type II]] and [[hypophosphatasia]]) can trigger vitamin B<sub>6</sub> deficiency-dependent [[epilepsy|epileptic seizures]] in infants. These are responsive to pyridoxal 5'-phosphate therapy.<ref name="Ghatge2021">{{cite journal |vauthors=Ghatge MS, Al Mughram M, Omar AM, Safo MK |title=Inborn errors in the vitamin B6 salvage enzymes associated with neonatal epileptic encephalopathy and other pathologies |journal=Biochimie |volume=183 |issue= |pages=18–29 |date=April 2021 |pmid=33421502 |doi=10.1016/j.biochi.2020.12.025 |s2cid=231437416 |url=|pmc=11273822 }}</ref><ref name="Mastrangelo2019">{{cite journal |vauthors=Mastrangelo M, Cesario S |title=Update on the treatment of vitamin B6 dependent epilepsies |journal=Expert Rev Neurother |volume=19 |issue=11 |pages=1135–47 |date=November 2019 |pmid=31340680 |doi=10.1080/14737175.2019.1648212 |s2cid=198496085 |url=}}</ref>

==History==
{{Further|Vitamin#History}}
An overview of the history was published in 2012.<ref name=Rosenberg2012/> In 1934, the Hungarian physician [[Paul Gyorgy|Paul György]] discovered a substance that was able to cure a skin disease in rats (dermatitis acrodynia). He named this substance vitamin B<sub>6</sub>, as numbering of the B vitamins was chronological, and [[pantothenic acid]] had been assigned vitamin B<sub>5</sub> in 1931.<ref>{{cite journal |doi=10.1038/133498a0 |title=Vitamin B2 and the Pellagra-like Dermatitis in Rats |journal=Nature |volume=133 |issue=3361 |pages=498–9 |year=1934 |last1=György |first1=Paul |bibcode=1934Natur.133..498G |s2cid=4118476 }}</ref><ref>{{cite journal | vauthors = György P, Eckardt RE | title = Further investigations on vitamin B(6) and related factors of the vitamin B(2) complex in rats. Parts I and II | journal = The Biochemical Journal | volume = 34 | issue = 8–9 | pages = 1143–54 | date = September 1940 | pmid = 16747297 | pmc = 1265394 | doi = 10.1042/bj0341143 }}</ref> In 1938, [[Richard Kuhn]] was awarded the [[Nobel Prize in Chemistry]] for his work on carotenoids and vitamins, specifically B<sub>2</sub> and B<sub>6</sub>.<ref name="Kuhn">{{cite web|url=https://www.nobelprize.org/nobel_prizes/chemistry/laureates/1938/index.html|title=The Nobel Prize in Chemistry 1938|access-date=July 5, 2018|website=Nobelprize.org|archive-date=July 8, 2018|archive-url=https://web.archive.org/web/20180708045113/https://www.nobelprize.org/nobel_prizes/chemistry/laureates/1938/index.html|url-status=live}}</ref> Also in 1938, Samuel Lepkovsky isolated vitamin B<sub>6</sub> from rice bran.<ref name=Rosenberg2012>{{cite journal |vauthors=Rosenberg IH |title=A history of the isolation and identification of vitamin B(6) |journal=Ann Nutr Metab |volume=61 |issue=3 |pages=236–8 |date=2012 |pmid=23183295 |doi=10.1159/000343113 |s2cid=37156675 |url=}}</ref> A year later, Stanton A. Harris and [[Karl August Folkers]] determined the structure of pyridoxine and reported success in [[chemical synthesis]],<ref>{{cite journal |vauthors=Harris SA, Folkers K |title=Synthetic vitamin B6 |journal=Science |volume=89 |issue=2311 |page=347 |date=April 1939 |pmid=17788439 |doi=10.1126/science.89.2311.347 |bibcode=1939Sci....89..347H |url=}}</ref> and then in 1942 [[Esmond Emerson Snell]] developed a microbiological growth [[assay]] that led to the characterization of pyridoxamine, the aminated product of pyridoxine, and pyridoxal, the [[formyl]] derivative of pyridoxine.<ref name=Rosenberg2012/> Further studies showed that pyridoxal, pyridoxamine, and pyridoxine have largely equal activity in animals and owe their vitamin activity to the ability of the organism to convert them into the enzymatically active form pyridoxal-5-phosphate.<ref name=Rosenberg2012 />

Following a recommendation of [[International Union of Pure and Applied Chemistry|IUPAC]]-IUB in 1973,<ref>{{cite journal|date=December 17, 1973|title=IUPAC-IUB commission on biochemical nomenclature (CBN). Nomenclature for vitamins B-6 and related compounds. Recommendations 1973|url=https://pubmed.ncbi.nlm.nih.gov/4781383/|journal=European Journal of Biochemistry|volume=40|issue=2|pages=325–327|issn=0014-2956|pmid=4781383|access-date=August 30, 2021|archive-date=June 2, 2022|archive-url=https://web.archive.org/web/20220602215236/https://pubmed.ncbi.nlm.nih.gov/4781383/|url-status=live}}</ref> vitamin B<sub>6</sub> is the official name for all 2-methyl,3-hydroxy,5-hydroxymethylpyridine derivatives exhibiting the biological activity of pyridoxine.<ref>{{cite journal|date=2016|title=Dietary Reference Values for vitamin B6|journal=EFSA Journal|language=en|volume=14|issue=6|pages=e04485|doi=10.2903/j.efsa.2016.4485|issn=1831-4732|doi-access=free|pmc=11847984 |pmid=40007837 | vauthors = Efsa Panel On Dietetic Products NA }}</ref> Because these related compounds have the same effect, the word "pyridoxine" should not be used as a synonym for vitamin B<sub>6</sub>.

==Research==
Observational studies suggested an [[inverse correlation]] between a higher intake of vitamin B<sub>6</sub> and all [[cancer]]s, with the strongest evidence for gastrointestinal cancers. However, evidence from a review of [[randomized controlled trial|randomized clinical trials]] did not support a protective effect. The authors noted that high B<sub>6</sub> intake may be an indicator of higher consumption of other dietary protective micronutrients.<ref>{{cite journal |vauthors=Mocellin S, Briarava M, Pilati P |title=Vitamin B6 and Cancer Risk: A Field Synopsis and Meta-Analysis |journal=J Natl Cancer Inst |volume=109 |issue=3 |pages=djw230 |date=March 2017 |pmid=28376200 |doi=10.1093/jnci/djw230 |url=|doi-access=free }}</ref> A review and two observational trials reporting lung cancer risk reported that serum vitamin B<sub>6</sub> was lower in people with lung cancer compared to people without lung cancer, but did not incorporate any intervention or prevention trials.<ref name=":1">{{cite journal |vauthors=Yang J, Li H, Deng H, Wang Z |title=Association of One-Carbon Metabolism-Related Vitamins (Folate, B6, B12), Homocysteine and Methionine With the Risk of Lung Cancer: Systematic Review and Meta-Analysis |journal=Front Oncol |volume=8 |issue= |pages=493 |date=2018 |pmid=30430082 |pmc=6220054 |doi=10.3389/fonc.2018.00493 |url=|doi-access=free }}</ref><ref>{{cite journal |last1=Fanidi |first1=A |last2=Muller |first2=DC |last3=Yuan |first3=J |last4=Stevens |first4=VL |last5=Weinstein |first5=SJ |date=January 2018 |title=Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3) |journal=Journal of the National Cancer Institute |volume=110 |issue=1 |pages=57–67 |doi=10.1093/jnci/djx119 |issn=1460-2105 |pmc=5989622 |pmid=28922778}}</ref><ref>{{cite journal |last1=Johansson |first1=M |last2=Relton |first2=C |last3=Ueland |first3=PM |last4=Vollset |first4=SE |last5=Midttun |first5=Ø |date=June 2010 |title=Serum B Vitamin Levels and Risk of Lung Cancer |journal=JAMA |volume=303 |issue=23 |pages=2377–85 |doi=10.1001/jama.2010.808 |pmid=20551408 |issn=0098-7484 |doi-access=free |url=https://researchonline.lshtm.ac.uk/id/eprint/2587/1/Serum%20B%20Vitamin%20Levels%20and%20Risk%20of%20Lung%20Cancer.pdf |access-date=March 20, 2024 |archive-date=November 21, 2023 |archive-url=https://web.archive.org/web/20231121064850/https://researchonline.lshtm.ac.uk/id/eprint/2587/1/Serum%20B%20Vitamin%20Levels%20and%20Risk%20of%20Lung%20Cancer.pdf |url-status=live }}</ref>

According to a prospective [[cohort study]] the long-term use of vitamin B<sub>6</sub> from individual supplement sources at greater than 20&nbsp;mg per day, which is more than ten times the adult male RDA of 1.7&nbsp;mg/day, was associated with an increased risk for lung cancer among men. Smoking further elevated this risk.<ref>{{cite journal|vauthors=Brasky TM, White E, Chen CL |date=October 2017|title=Long-Term, Supplemental, One-Carbon Metabolism-Related Vitamin B Use in Relation to Lung Cancer Risk in the Vitamins and Lifestyle (VITAL) Cohort|journal=Journal of Clinical Oncology |volume=35|issue=30|pages=3440–3448|doi=10.1200/JCO.2017.72.7735|issn=1527-7755|pmc=5648175|pmid=28829668}}</ref> However, a more recent review of this study suggested that a causal relationship between supplemental vitamin B<sub>6</sub> and an increased lung cancer risk cannot be confirmed yet.<ref>{{cite journal |last1=Calderon-Ospina |first1=CA |last2=Nava-Mesa |first2=MO |last3=Paez-Hurtado |first3=AM |date=2020 |title=Update on Safety Profiles of Vitamins B1, B6, and B12: A Narrative Review |journal=Therapeutics and Clinical Risk Management |volume=16 |pages=1275–88 |doi=10.2147/TCRM.S274122 |issn=1176-6336 |pmc=7764703 |pmid=33376337 |doi-access=free }}</ref>

For [[coronary heart disease]], a [[meta-analysis]] reported lower relative risk for a 0.5&nbsp;mg/day increment in dietary vitamin B<sub>6</sub> intake.<ref>{{cite journal |vauthors=Jayedi A, Zargar MS |title=Intake of vitamin B6, folate, and vitamin B12 and risk of coronary heart disease: a systematic review and dose-response meta-analysis of prospective cohort studies |journal=Crit Rev Food Sci Nutr |volume=59 |issue=16 |pages=2697–707 |date=2019 |pmid=30431328 |doi=10.1080/10408398.2018.1511967 |s2cid=53430399 |url=}}</ref> As of 2021, there were no published reviews of randomized clinical trials for coronary heart disease or cardiovascular disease. In reviews of observational and intervention trials, neither higher vitamin B<sub>6</sub> concentrations<ref>{{cite journal |vauthors=Zhang C, Luo J, Yuan C, Ding D |title=Vitamin B12, B6, or Folate and Cognitive Function in Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis |journal=J Alzheimers Dis |volume=77 |issue=2 |pages=781–94 |date=2020 |pmid=32773392 |doi=10.3233/JAD-200534 |s2cid=221100310 |url=}}</ref> nor treatment<ref>{{cite journal |vauthors=Ford AH, Almeida OP |title=Effect of Vitamin B Supplementation on Cognitive Function in the Elderly: A Systematic Review and Meta-Analysis |journal=Drugs Aging |volume=36 |issue=5 |pages=419–34 |date=May 2019 |pmid=30949983 |doi=10.1007/s40266-019-00649-w |s2cid=96435344 |url=}}</ref> showed any significant benefit on [[cognition]] and [[dementia]] risk. Low dietary vitamin B<sub>6</sub> correlated with a higher risk of [[depression (mood)|depression]] in women but not in men.<ref>{{cite journal |vauthors=Wu Y, Zhang L, Li S, Zhang D |title=Associations of dietary vitamin B1, vitamin B2, vitamin B6, and vitamin B12 with the risk of depression: a systematic review and meta-analysis |journal=Nutr Rev |volume= 80|issue= 3|pages= 351–366|date=April 2021 |pmid=33912967 |doi=10.1093/nutrit/nuab014 |url=}}</ref> When treatment trials were reviewed, no meaningful treatment effect for depression was reported, but a subset of trials in [[pre-menopausal]] women suggested a benefit, with a recommendation that more research was needed.<ref>{{cite journal |vauthors=Williams AL, Cotter A, Sabina A, Girard C, Goodman J, Katz DL |title=The role for vitamin B-6 as treatment for depression: a systematic review |journal=Fam Pract |volume=22 |issue=5 |pages=532–7 |date=October 2005 |pmid=15964874 |doi=10.1093/fampra/cmi040 |url=|doi-access= }}</ref> The results of several trials with children diagnosed as having [[autism spectrum disorder]] (ASD) treated with high dose vitamin B<sub>6</sub> and [[magnesium]] did not result in treatment effect on the severity of symptoms of ASD.<ref>{{cite journal |vauthors=Li YJ, Li YM, Xiang DX |title=Supplement intervention associated with nutritional deficiencies in autism spectrum disorders: a systematic review |journal=Eur J Nutr |volume=57 |issue=7 |pages=2571–82 |date=October 2018 |pmid=28884333 |doi=10.1007/s00394-017-1528-6 |s2cid=3999214 |url=}}</ref>

== References ==
{{Reflist|30em}}

== External links ==
* [http://bioinformatics.unipr.it/cgi-bin/bioinformatics/B6db/home.pl The B<sub>6</sub> database] {{Webarchive|url=https://web.archive.org/web/20060327224058/http://bioinformatics.unipr.it/cgi-bin/bioinformatics/B6db/home.pl |date=March 27, 2006 }} A database of B<sub>6</sub>-dependent enzymes at [[University of Parma]]
* {{MeSH name|Vitamin+B6}}

{{Vitamins}}
{{Authority control}}

[[Category:B vitamins|Vitamin B06]]
[[Category:Cofactors]]