Vitamin B6

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Pyridoxine deficiency
)
This article is about the group of
vitamers. For the dietary supplement, see Pyridoxine
.

Vitamin B6
A11H
Biological targetenzyme cofactor
Clinical data
Drugs.comInternational Drug Names
External links
MeSHD025101
Legal status
In Wikidata

Vitamin B6 is one of the

coenzyme in more than 140 enzyme reactions in amino acid, glucose, and lipid metabolism.[1][2][3]

Plants synthesize pyridoxine as a means of protection from the

vegan diet does not put consumers at risk for deficiency.[7]

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 and motor nerves in the hands and feet. In addition to dietary shortfall, deficiency can be the result of anti-vitamin drugs. There are also rare genetic defects that can trigger vitamin B6 deficiency-dependent epileptic seizures in infants. These are responsive to pyridoxal 5'-phosphate therapy.[8]

Definition

Pyridoxine (PN)
Pyridoxamine (PM)
Pyridoxal (PL)

Vitamin B6 is a water-soluble vitamin, one of the B vitamins. The vitamin actually comprises a group of six chemically related compounds, i.e., vitamers, that all contain a pyridine ring as their core. These are pyridoxine, pyridoxal, pyridoxamine, and their respective phosphorylated derivatives pyridoxine 5'-phosphate, pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate. Pyridoxal 5'-phosphate has the highest biological activity, but the others are convertible to that form.[9] Vitamin B6 serves as a 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.[1][2][3]

Forms

Because of its chemical stability, pyridoxine hydrochloride is the form most commonly given as vitamin B6 dietary supplement. Absorbed pyridoxine (PN) is converted to pyridoxamine 5'-phosphate (PMP) by the enzyme

pyridoxine 5'-phosphate oxidase, the latter of which also catalyzes the conversion of pyridoxine 5′-phosphate (PNP) to PLP.[3][9] Pyridoxine 5'-phosphate oxidase is dependent on flavin mononucleotide (FMN) as a cofactor produced from riboflavin (vitamin B2). For degradation, in a non-reversible reaction, PLP is catabolized to 4-pyridoxic acid, which is excreted in urine.[3]

Synthesis

Biosynthesis

Main article: 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[10] and Bacillus subtilis, respectively. Despite the disparity in the starting compounds and the different number of steps required, the two pathways possess many commonalities.[11] The DXP-dependent pathway:

Commercial synthesis

The starting material is either the amino acid

pyridoxine hydrochloride, the chemically stable hydrochloride salt of pyridoxine.[13] 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.[14] Fermentative bacterial biosynthesis methods are also being explored, but are not yet scaled up for commercial production.[13]

Functions

PLP is involved in many aspects of macronutrient metabolism,

replacement, and beta-group interconversion.[2][3][15]

Amino acid metabolism

  1. 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.[3]
  2. D-serine from its enantiomer
    is a PLP-dependent enzyme.
  3. PLP is a coenzyme needed for the proper function of the enzymes
    cystathionase) also produces cysteine
    .
  4. 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 selenoproteins.
  5. PLP is required for the conversion of
    niacin, so low vitamin B6 status impairs this conversion.[15]

Neurotransmitters

  1. PLP is a cofactor in the biosynthesis of five important
    gamma-aminobutyric acid.[6]

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.[6] PLP also catalyzes transamination reactions that are essential for providing amino acids as a substrate for gluconeogenesis, the biosynthesis of glucose.[15]

Lipid metabolism

PLP is an essential component of enzymes that facilitate the biosynthesis of

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.[6] It also binds to two sites on hemoglobin to enhance the oxygen binding of hemoglobin.[15]

Gene expression

PLP has been implicated in increasing or decreasing the expression of certain

mRNA. Also, PLP influences expression of glycoprotein IIb by interacting with various transcription factors; the result is inhibition of platelet aggregation.[15]

In plants

Plant synthesis of vitamin B6 contributes to protection from sunlight.

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 inducible, and as a consequence, ROS levels, lipid peroxidation, and cell proteins associated with tissue damage were all elevated.[5][16][17] 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.[6] In addition, plant mutants with severely limited capacity to synthesize vitamin B6 have stunted root growth, because synthesis of plant hormones such as auxin require the vitamin as an enzyme cofactor.[6]

Medical uses

Further information: Pyridoxine

Isoniazid is an antibiotic used for the treatment of tuberculosis. Common side effect include numbness in the hands and feet, also known as peripheral neuropathy.[18] Co-treatment with vitamin B6 alleviates the numbness.[19]

Overconsumption of seeds from Ginkgo biloba can deplete vitamin B6, because the ginkgotoxin is an anti-vitamin (vitamin antagonist). Symptoms include vomiting and generalized convulsions. Ginkgo seed poisoning can be treated with vitamin B6.[20][21]

Dietary recommendations

The US

Tolerable upper intake levels (ULs) for vitamins and minerals are identified when evidence is sufficient. In the case of vitamin B6 the adult UL is set at 100 mg/day.[4]

The European Food Safety Authority (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 mg/day, respectively; for pregnancy 1.8 mg/day, for lactation 1.7 mg/day. For children ages 1–14 years the PRIs increase with age from 0.6 to 1.4 mg/day.[22] The EFSA also reviewed the safety question and set its UL at 25 mg/day.[23][24]

The Japanese Ministry of Health, Labour and Welfare updated its vitamin and mineral recommendations in 2015. The adult RDAs are at 1.2 mg/day for women 1.4 mg/day for men. The RDA for pregnancy is 1.4 mg/day, for lactation is 1.5 mg/day. For children ages 1–17 years the RDA increases with age from 0.5 to 1.5 mg/day. The adult UL was set at 40–45 mg/day for women and 50–60 mg/day for men, with the lower values in those ranges for adults over 70 years of age.[25]

Safety

Main article: Megavitamin-B6 syndrome

Adverse effects have been documented from vitamin B6 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.

neuropathy typically develops at doses of pyridoxine in excess of 1,000 mg per day, but adverse effects can occur with much less, so intakes over 200 mg/day are not considered safe.[4] Trials with amounts equal to or less than 200 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 mg/day.[4]

Labeling

For US food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value. For vitamin B6 labeling purposes 100% of the Daily Value was 2.0 mg, but as of May 27, 2016, it was revised to 1.7 mg to bring it into agreement with the adult RDA.[26][27] 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 B6, but the amounts are not sufficient to meet host requirements, in part because the vitamins are competitively taken up by non-synthesizing bacteria.[28]

Vitamin B6 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).[29][30] Crustaceans and mollusks contain about 0.1 mg/100 grams. Fruit (apples, oranges, pears) contain less than 0.1 mg/100g.[30]

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 B6 because removal of the glucoside by intestinal cells is not 100% efficient.[4] 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 B6 deficiency.[7]

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.

dried.[15] The vitamin is found in the germ and aleurone layer of grains, so there is more in whole wheat bread compared to white bread wheat, and more in brown rice compared to white rice.[30]

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

Source[29][30] Amount
(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, ground, cooked 0.6
Banana 0.4
Source[29][30] Amount
(mg per 100 grams)
Mushroom, Shiitake, raw 0.3
Potato, baked, with skin 0.3
Sweet potato baked 0.3
Bell pepper, red 0.3
Peanuts 0.3
Avocado 0.25
Spinach 0.2
Chickpeas
 0.1
Tofu, firm 0.1
Source[30] Amount
(mg per 100 grams)
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
Beans, baked 0.1
Beans, green 0.1
Chicken egg
 0.1

Fortification

As of 2019, fourteen countries require food fortification of wheat flour, maize flour or rice with vitamin B6 as pyridoxine hydrochloride. Most of these are in southeast Africa or Central America. The amounts stipulated range from 3.0 to 6.5 mg/kg. An additional seven countries, including India, have a voluntary fortification program. India stipulates 2.0 mg/kg.[31]

Dietary supplements

In the US, multi-vitamin/mineral products typically contain 2 to 4 mg of vitamin B6 per daily serving as pyridoxine hydrochloride, but a few contain more than 25 mg. Many US dietary supplement companies also market a B6-only dietary supplement with 100 mg per daily serving.

US National Academy of Medicine sets an adult safety UL at 100 mg/day,[1][4] the European Food Safety Authority sets its UL at 25 mg/day.[23][24]

Health claims

The Japanese Ministry of Health, Labor, and Welfare (MHLW) set up the 'Foods for Specified Health Uses' (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' (保健機能食品; FHC), which consists of the existing FOSHU system and the newly established 'Foods with Nutrient Function Claims' (栄養機能表示食品; FNFC), under which claims were approved for any product containing a specified amount per

mucous membranes."[34][35]

In 2010, the European Food Safety Authority (EFSA) published a review of proposed health claims for vitamin B6, 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.[36]

The US Food and Drug Administration (FDA) has several processes for permitting health claims on food and dietary supplement labels.[37] There are no FDA-approved Health Claims or Qualified Health Claims for vitamin B6. Structure/Function Claims can be made without FDA review or approval as long as there is some credible supporting science.[37] Examples for this vitamin are "Helps support nervous system function" and "Supports healthy homocysteine metabolism."

Absorption, metabolism and excretion

Vitamin B6 is absorbed in the

passive diffusion.[1][4] Even extremely large amounts are well absorbed. Absorption of the phosphate forms involves their dephosphorylation catalyzed by the enzyme alkaline phosphatase.[15] 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.[4] 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 mg.[4]

Enzymatic processes utilize PLP as a phosphate-donating cofactor. PLP is restored via a

pyridoxine 5'-phosphate oxidase, and phosphatases.[6][8] 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.[8]

The half-life of vitamin B6 varies according to different sources: one source suggests that the half-life of pyridoxine is up to 20 days,[38] while another source indicates half-life of vitamin B6 is in range of 25 to 33 days.[39] After considering the different sources, it can be concluded that the half-life of vitamin B6 is typically measured in several weeks.[38][39]

The end-product of vitamin B6 catabolism is 4-pyridoxic acid, which makes up about half of the B6 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.[4][40] 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 B6 is also excreted in the feces. This may be a combination of unabsorbed vitamin and what was synthesized by large intestine microbiota.[4]

Deficiency

Signs and symptoms

The classic clinical syndrome for vitamin B6 deficiency is a

neuropathy (due to impaired sphingosine synthesis).[1]

In infants, a deficiency in vitamin B6 can lead to irritability, abnormally acute hearing, and convulsive seizures.[1]

Less severe cases present with metabolic disease associated with insufficient activity of the

glucose tolerance.[1][15]

Diagnosis

The assessment of vitamin B6 status is essential, as the clinical signs and symptoms in less severe cases are not specific.[41] 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 B6 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 nmol/L is indicative of vitamin B6 deficiency.[40] A PLP concentration greater than 20 nmol/L has been chosen as a level of adequacy for establishing Estimated Average Requirements and Recommended Daily Allowances in the USA.[4] Urinary PA is also an indicator of vitamin B6 deficiency; levels of less than 3.0 mmol/day is suggestive of vitamin B6 deficiency.[40] Other methods of measurement, including UV spectrometric, spectrofluorimetric, mass spectrometric, thin-layer and high-performance liquid chromatographic, electrophoretic, electrochemical, and enzymatic, have been developed.[40][42]

The classic clinical symptoms for vitamin B6 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.[43]

Causes

A deficiency of vitamin B6 alone is relatively uncommon and often occurs in association with other vitamins of the B complex. Evidence exists for decreased levels of vitamin B6 in women with

oral contraceptives and treatment with certain anticonvulsants, isoniazid, cycloserine, penicillamine, and hydrocortisone negatively impact vitamin B6 status.[1][46][47] Hemodialysis reduces vitamin B6 plasma levels.[48]

Genetic defects

Genetically confirmed diagnoses of diseases affecting vitamin B6 metabolism (

hyperprolinaemia type II and hypophosphatasia) can trigger vitamin B6 deficiency-dependent epileptic seizures in infants. These are responsive to pyridoxal 5'-phosphate therapy.[8][49]

History

Further information: Vitamin § History

An overview of the history was published in 2012.

formyl derivative of pyridoxine.[50] 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.[50]

Following a recommendation of IUPAC-IUB in 1973,[55] vitamin B6 is the official name for all 2-methyl,3-hydroxy,5-hydroxymethylpyridine derivatives exhibiting the biological activity of pyridoxine.[56] Because these related compounds have the same effect, the word "pyridoxine" should not be used as a synonym for vitamin B6.

Research

Observational studies suggested an

inverse correlation between a higher intake of vitamin B6 and all cancers, with the strongest evidence for gastrointestinal cancers. However, evidence from a review of randomized clinical trials did not support a protective effect. The authors noted that high B6 intake may be an indicator of higher consumption of other dietary protective micronutrients.[57] A review and two observational trials reporting lung cancer risk reported that serum vitamin B6 was lower in people with lung cancer compared to people without lung cancer, but did not incorporate any intervention or prevention trials.[58][59][60]

According to a prospective cohort study the long-term use of vitamin B6 from individual supplement sources at greater than 20 mg per day, which is more than ten times the adult male RDA of 1.7 mg/day, was associated with an increased risk for lung cancer among men. Smoking further elevated this risk.[61] However, a more recent review of this study suggested that a causal relationship between supplemental vitamin B6 and an increased lung cancer risk cannot be confirmed yet.[62]

For

autism spectrum disorder (ASD) treated with high dose vitamin B6 and magnesium did not result in treatment effect on the severity of symptoms of ASD.[68]

References

  1. ^ a b c d e f g h i j k "Facts about Vitamin B6 Fact Sheet for Health Professionals". Office of Dietary Supplements at National Institutes of Health. February 24, 2020. Archived from the original on April 18, 2011. Retrieved February 5, 2021.
  2. ^ a b c d "Vitamin B6". Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR. May 2014. Archived from the original on March 14, 2018. Retrieved March 7, 2017.
  3. ^
    ISBN 978-0-323-66162-1
    .
  4. ^
    PMID 23193625. Archived
    from the original on March 6, 2022. Retrieved April 20, 2018.
  5. ^
    PMID 19903353
    .
  6. ^
    PMID 30037155
    .
  7. ^
    PMID 34066199
    .
  8. ^
    S2CID 231437416
    .
  9. ^
    PMID 30142892
    .
  10. PMID 16157873
    .
  11. S2CID 28231094
    .
  12. PMID 23208776
    .
  13. ^
    PMID 34222212
    .
  14. doi:10.1021/op4001687. Archived
    from the original on May 22, 2022. Retrieved August 16, 2021.
  15. ^
    OCLC 150255807. Archived
    from the original on December 31, 2023. Retrieved April 20, 2018.
  16. PMID 21288732. Archived
    from the original on January 6, 2024. Retrieved March 20, 2024.
  17. PMID 30718682
    .
  18. ^ "Isoniazid". The American Society of Health-System Pharmacists. Archived from the original on December 20, 2016. Retrieved August 13, 2021.
  19. S2CID 39197646
    .
  20. PMID 28055331
    .
  21. PMID 30606915
    .
  22. ^ "Overview on Dietary Reference Values for the EU population as derived by the EFSA Panel on Dietetic Products, Nutrition and Allergies" (PDF). 2017. Archived (PDF) from the original on August 28, 2017.
  23. ^ a b "Tolerable Upper Intake Levels For Vitamins And Minerals" (PDF). European Food Safety Authority. 2006. Archived (PDF) from the original on September 19, 2017.
  24. ^
    PMID 37213840. Archived
    from the original on October 24, 2020. Retrieved September 22, 2019.
  25. ^ "Overview of Dietary Reference Intakes for Japanese" (PDF). Ministry of Health, Labour and Welfare (Japan). 2015. Archived (PDF) from the original on October 21, 2022. Retrieved August 19, 2021.
  26. ^ "Federal Register May 27, 2016 Food Labeling: Revision of the Nutrition and Supplement Facts Labels" (PDF). Archived (PDF) from the original on September 22, 2017.
  27. ^ "Daily Value Reference of the Dietary Supplement Label Database (DSLD)". Dietary Supplement Label Database (DSLD). Archived from the original on April 7, 2020. Retrieved May 16, 2020.
  28. PMID 33147768
    .
  29. ^ a b c Joseph M (January 10, 2021). "30 Foods High In Vitamin B6". Nutrition Advance. Archived from the original on July 19, 2022. Retrieved August 17, 2021. All nutritional values within this article have been sourced from the USDA's FoodData Central Database.
  30. ^ a b c d e f "USDA Food Data Central. Standard Reference, Legacy Foods". USDA Food Data Central. April 2018. Archived from the original on December 3, 2019. Retrieved August 18, 2021.
  31. ^ "Map: Count of Nutrients In Fortification Standards". Global Fortification Data Exchange. August 16, 2021. Archived from the original on April 11, 2019. Retrieved August 16, 2021.
  32. PMID 19087392
    .
  33. ISSN 0525-1931. Archived
    from the original on February 10, 2023. Retrieved September 23, 2021.
  34. ^ Shimizu T (2001). "新しい保健機能性食晶制度の概要" [Newly Established Regulation: Foods with Health Claims] (PDF). Journal of the International Life Sciences Institute of Japan (in Japanese). 66: 9–15. Archived (PDF) from the original on February 24, 2023. Retrieved September 23, 2021.
  35. Ministry of Health, Labor, and Welfare (in Japanese). Archived from the original
    on September 23, 2021. Retrieved September 23, 2021. ビタミンB6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.
  36. doi:10.2903/j.efsa.2010.1759
    .
  37. ^ a b "Label Claims for Conventional Foods and Dietary Supplements". U.S. Food and Drug Administration. June 19, 2018. Archived from the original on August 17, 2021. Retrieved August 17, 2021.
  38. ^
    ISBN 978-3-319-20790-2
    . The half-life of pyridoxine is up to 20 days.
  39. ^
    ISBN 978-82-8259-260-4. Archived from the original
    (PDF) on November 17, 2019. Retrieved December 7, 2019. 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.
  40. ^
    PMID 25974692
    .
  41. OCLC 884490740. Archived
    from the original on December 31, 2023. Retrieved April 20, 2018.
  42. PMID 24035968
    .
  43. OCLC 925196268. Archived
    from the original on December 31, 2023. Retrieved April 20, 2018.
  44. PMID 22288928
    .
  45. PMID 24808485
    .
  46. PMID 21967158
    .
  47. PMID 10080517
    .
  48. S2CID 22894817
    .
  49. S2CID 198496085
    .
  50. ^
    S2CID 37156675
    .
  51. S2CID 4118476
    .
  52. PMID 16747297
    .
  53. ^ "The Nobel Prize in Chemistry 1938". Nobelprize.org. Archived from the original on July 8, 2018. Retrieved July 5, 2018.
  54. PMID 17788439
    .
  55. PMID 4781383. Archived
    from the original on June 2, 2022. Retrieved August 30, 2021.
  56. ISSN 1831-4732
    .
  57. PMID 28376200
    .
  58. PMID 30430082
    .
  59. PMID 28922778
    .
  60. PMID 20551408. Archived
    (PDF) from the original on November 21, 2023. Retrieved March 20, 2024.
  61. PMID 28829668
    .
  62. PMID 33376337
    .
  63. S2CID 53430399
    .
  64. S2CID 221100310
    .
  65. S2CID 96435344
    .
  66. PMID 33912967
    .
  67. PMID 15964874
    .
  68. S2CID 3999214
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Vitamin_B6&oldid=1218705675#Deficiency"