Vitamin B6

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Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate (PLP) is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation. PLP also is necessary for the enzymatic reaction governing the release of glucose from glycogen.

History[edit]

In 1934, the Hungarian physician Paul Gyorgy discovered a substance that was able to cure a skin disease in rats (dermititis acrodynia). He named this substance vitamin B6.[1][2] In 1938, Samuel Lepkovsky isolated vitamin B6 from rice bran. Harris and Folkers in 1939 determined the structure of pyridoxine, and, in 1945, Snell was able to show the two forms of vitamin B6, pyridoxal and pyridoxamine. Vitamin B6 was named pyridoxine to indicate its structural homology to pyridine. All three forms of vitamin B6 are precursors of an activated compound known as pyridoxal 5'-phosphate (PLP), which plays a vital role as the cofactor of a large number of essential enzymes in the human body.

Enzymes dependent on PLP focus a wide variety of chemical reactions mainly involving amino acids. The reactions carried out by the PLP-dependent enzymes that act on amino acids include transfer of the amino group, decarboxylation, racemization, and beta- or gamma-elimination or replacement. Such versatility arises from the ability of PLP to covalently bind the substrate, and then to act as an electrophilic catalyst, thereby stabilizing different types of carbanionic reaction intermediates.

Overall, the Enzyme Commission has catalogued more than 140 PLP-dependent activities, corresponding to ~4% of all classified activities.[3]

Forms[edit]

Seven forms of this vitamin are known:

  • Pyridoxine (PN), the form that is most commonly given as vitamin B6 supplement
  • Pyridoxine 5'-phosphate (PNP)
  • Pyridoxal (PL)
  • Pyridoxal 5'-phosphate (PLP), the metabolically active form (sold as 'P-5-P' vitamin supplement)
  • Pyridoxamine (PM)
  • Pyridoxamine 5'-phosphate (PMP)
  • 4-Pyridoxic acid (PA), the catabolite which is excreted in the urine

All forms except PA can be interconverted.

Functions[edit]

Pyridoxal phosphate, the metabolically active form of vitamin B6, is involved in many aspects of macronutrient metabolism, neurotransmitter synthesis, histamine synthesis, hemoglobin synthesis and function and gene expression. Pyridoxal phosphate generally serves as a coenzyme for many reactions and can help facilitate decarboxylation, transamination, racemization, elimination, replacement and beta-group interconversion reactions.[4] The liver is the site for vitamin B6 metabolism.

Amino acid metabolism[edit]

Pyridoxal phosphate (PLP) is a cofactor in transaminases that can catabolize amino acids. PLP is also an essential component of two enzymes that convert methionine to cysteine via two reactions. Low vitamin B6 status will result in decreased activity of these enzymes. PLP is also an essential cofactor for enzymes involved in the metabolism of selenomethionine to selenohomocysteine and then from selenohomocysteine to hydrogen selenide. Vitamin B6 is also required for the conversion of tryptophan to niacin and low vitamin B6 status will impair this conversion.[4] PLP is also used to create physiologically active amines by decarboxylation of amino acids. Some notable examples of this include: histidine to histamine, tryptophan to serotonin, glutamate to gamma-aminobutyric acid (GABA), and dihydroxyphenylalanine to dopamine.

Gluconeogenesis[edit]

Vitamin B6 also plays a role in gluconeogenesis. Pyridoxal phosphate can catalyze transamination reactions that are essential for the providing amino acids as a substrate for gluconeogenesis. Also, vitamin B6 is a required coenzyme of glycogen phosphorylase,[4] the enzyme necessary for glycogenolysis to occur.

Lipid metabolism[edit]

Vitamin B6 is an essential component of enzymes that facilitate the biosynthesis of sphingolipids.[4] 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. Dihydroceramide is then further desaturated to form ceramide. In addition, the breakdown of sphingolipids is also dependent on vitamin B6 because S1P lyase, the enzyme responsible for breaking down sphingosine-1-phosphate, is also PLP-dependent.

Metabolic functions[edit]

The primary role of vitamin B6 is to act as a coenzyme to many other enzymes in the body that are involved predominantly in metabolism. This role is performed by the active form, pyridoxal phosphate. This active form is converted from the other natural forms found in food: pyridoxal, pyridoxine and pyridoxamine.[5]

Vitamin B6 is involved in the following metabolic processes:

  • amino acid, glucose and lipid metabolism
  • neurotransmitter synthesis
  • histamine synthesis
  • hemoglobin synthesis and function
  • gene expression

Amino acid metabolism[edit]

Pyridoxal phosphate is involved in almost all amino acid metabolism, from synthesis to breakdown.

  1. Transamination: Transaminase enzymes needed to break down amino acids are dependent on the presence of pyridoxal phosphate. The proper activity of these enzymes is crucial for the process of moving amine groups from one amino acid to another.
  2. Trans-sulfuration: Pyridoxal phosphate is a coenzyme needed for the proper function of the enzymes cystathionine synthase and cystathionase. These enzymes work to transform methionine into cysteine.
  3. Selenoamino acid metabolism: Selenomethionine is the primary dietary form of selenium. Pyridoxal phosphate is needed as a cofactor for the enzymes that allow selenium to be used from the dietary form. Pyridoxal phosphate also plays a cofactor role in releasing selenium from selenohomocysteine to produce hydrogen selenide, which can then be used to incorporate selenium into selenoproteins.[4]
  4. Vitamin B6 is also required for the conversion of tryptophan to niacin, so low vitamin B6 status will impair this conversion.[4]

Neurotransmitter synthesis[edit]

Pyridoxal phosphate-dependent enzymes play a role in the biosynthesis of five important neurotransmitters: serotonin, dopamine, epinephrine, norepinephrine and gamma-aminobutyric acid (GABA).[4] Serine racemase, which synthesizes the neuromodulator D-serine, is also a pyridoxal phosphate-dependent enzyme.

Histamine synthesis[edit]

Pyridoxal phosphate is involved in the metabolism of histamine.[4]

Hemoglobin synthesis and function[edit]

Pyridoxal phosphate aids in the synthesis of hemoglobin, by serving as a coenzyme for the enzyme ALA synthase.[6] It also binds to two sites on hemoglobin to enhance the oxygen binding of hemoglobin.[4]

Gene expression[edit]

It transforms homocysteine into cystathionine then into cysteine. Pyridoxal phosphate has been implicated in increasing or decreasing the expression of certain genes. Increased intracellular levels of the vitamin will lead to a decrease in the transcription of glucocorticoid hormones. Also, vitamin B6 deficiency will lead to the increased expression of albumin mRNA. Also, pyridoxal phosphate will influence gene expression of glycoprotein IIb by interacting with various transcription factors. The result is inhibition of platelet aggregation.[4]

Dietary reference intakes[edit]

The Institute of Medicine notes, "No adverse effects associated with vitamin B6 from food have been reported. This does not mean that there is no potential for adverse effects resulting from high intakes. Because data on the adverse effects of vitamin B6 are limited, caution may be warranted. Sensory neuropathy has occurred from high intakes of supplemental forms."[7] See the full Dietary Reference Intake Table [8] from the Institute of Medicine.

Food sources[edit]

Vitamin B6 is widely distributed in foods in both its free and bound forms. Good sources include meats, whole grain products, vegetables, nuts and bananas. Cooking, storage, and processing losses of vitamin B6 vary and in some foods may be more than 50%,[9] depending on the form of vitamin present in the food. Plant foods lose the least during processing, as they contain mostly pyridoxine, which is far more stable than the pyridoxal or pyridoxamine found in animal foods. For example, milk can lose 30 to 70% of its vitamin B6 content when dried.[4] Vitamin B6 is found in the germ and aleurone layer of grains, and milling results in the reduction of this vitamin in white flour. Freezing and canning are other food processing methods that result in the loss of vitamin B6 in foods.[10]

The best natural sources include avocados, brewer's yeast, wheat bran, wheat germ, liver, kidney, heart, blackstrap molasses, milk, eggs, beef.[11][12]

Absorption and excretion[edit]

Vitamin B6 is absorbed in the jejunum and ileum via passive diffusion. With the capacity for absorption being so great, animals are able to absorb quantities much greater than necessary for physiological demands. The absorption of pyridoxal phosphate and pyridoxamine phosphate involves their dephosphorylation catalyzed by a membrane-bound alkaline phosphatase. Those products and non-phosphorylated vitamers in the digestive tract are absorbed by diffusion, which is driven by trapping of the vitamin as 5'-phosphates through the action of phosphorylation (by a pyridoxal kinase) in the jejunal mucosa. The trapped pyridoxine and pyridoxamine are oxidized to pyridoxal phosphate in the tissue.[4]

The products of vitamin B6 metabolism are excreted in the urine, the major product of which is 4-pyridoxic acid. It has been estimated that 40–60% of ingested vitamin B6 is oxidized to 4-pyridoxic acid. Several studies have shown that 4-pyridoxic acid is undetectable in the urine of vitamin B6 deficient subjects, making it a useful clinical marker to assess the vitamin B6 status of an individual.[4] Other products of vitamin B6 metabolism that are excreted in the urine when high doses of the vitamin have been given include pyridoxal, pyridoxamine, and pyridoxine and their phosphates. A small amount of vitamin B6 is also excreted in the feces.

Deficiencies[edit]

The classic clinical syndrome for B6 deficiency is a seborrhoeic dermatitis-like eruption, atrophic glossitis with ulceration, angular cheilitis, conjunctivitis, intertrigo, and neurologic symptoms of somnolence, confusion, and neuropathy.[13]

While severe vitamin B6 deficiency results in dermatologic and neurologic changes, less severe cases present with metabolic lesions associated with insufficient activities of the coenzyme pyridoxal phosphate. The most prominent of the lesions is due to impaired tryptophan-niacin conversion. This can be detected based on urinary excretion of xanthurenic acid after an oral tryptophan load. Vitamin B6 deficiency can also result in impaired transsulfuration of methionine to cysteine. The pyridoxal phosphate-dependent transaminases and glycogen phosphorylase provide the vitamin with its role in gluconeogenesis, so deprivation of vitamin B6 results in impaired glucose tolerance.[4]

A deficiency of vitamin B6 alone is relatively uncommon and often occurs in association with other vitamins of the B complex. The elderly and alcoholics have an increased risk of vitamin B6 deficiency, as well as other micronutrient deficiencies.[14] Renal patients undergoing dialysis may experience vitamin B6 deficiency. Also, patients with liver disease, rheumatoid arthritis, women with type 1 diabetes, and those infected with HIV also appear to be at risk, despite adequate dietary intakes.[15][16] The availability of vitamin B6 to the body can be affected by certain drugs such as anticonvulsants and corticosteroids.[10] The drug isoniazid (used in the treatment of tuberculosis), and cycloserine, penicillamine, and hydrocortisone all interfere with vitamin B6 metabolism. These drugs may form a complex with vitamin B6 that is inhibitory for pyridoxal kinase, or they may positively displace PLP from binding sites.[17]

Clinical assessment of vitamin B6[edit]

The biochemical assessment of vitamin B6 status is essential, as the clinical signs and symptoms of its deficiency are very nonspecific.[18] The three biochemical tests most widely used are the activation coefficient for the erythrocyte enzyme aspartate aminotransferase, plasma pyridoxal phosphate (PLP) concentrations, and the urinary excretion of vitamin B6 degradation products, specifically urinary pyridoxic acid. Of these, plasma PLP is probably the best single measure, because it reflects tissue stores.[19] When plasma pyridoxal phosphate is less than 10nmol/L, it is indicative of vitamin B6 deficiency.[19] A PLP concentration greater than 20nmol/L has been chosen as a level of adequacy for establishing Estimated Average Requirements and Recommended Daily Allowances in the USA.[20] Urinary 4-pyridoxic acid is also an indicator of vitamin B6 deficiency; levels of less than 3.0 mmol/day is suggestive of vitamin B6 deficiency.[21]

Toxicity[edit]

Adverse effects have been documented from vitamin B6 supplements but never from food sources. This article discusses only the safety of the common supplemental form of vitamin B6, pyridoxine (for a full discussion please see pyridoxine). Toxicologic animal studies identify specific destruction of the dorsal root ganglia[22] which is documented in human cases of overdosage of pyridoxine.[23] Although it is a water-soluble vitamin and is excreted in the urine, doses of pyridoxine in excess of the RDI over long periods of time result in painful and ultimately irreversible neurological problems.

The primary symptoms are pain and numbness of the extremities. In severe cases, there may also be motor neuropathy with "slowing of motor conduction velocities, prolonged F wave latencies, and prolonged sensory latencies in both lower extremities" causing difficulty in walking.[24] Sensory neuropathy typically develops at doses of pyridoxine in excess of 1,000 mg per day but adverse effects can occur with much less and, therefore, doses over 200 mg are not considered safe.[25] Symptoms among women taking lower doses have been reported.[26] Two reported cases of neuropathy with pyridoxine treatment of 24 and 40 mg/day may have been coincidental.[25] This condition is usually reversible when supplementation is stopped.[27]

Existing authorisations and valuations vary considerably worldwide. In 1993, the European Community Scientific Committee on Food defined intakes of 50 mg of vitamin B6 per day as harmful and established a tolerable upper intake level of 25 mg/day for adults in 2000.

The Expert Group on Vitamins and Minerals of the Food Standard Agency UK (UK EVM) derived a safe upper level (SUL) of 10 mg/day for a 60-kg adult in 2003.

The tolerable upper limit has been set by the US FDA at 100 mg/day in 2000.[28] The nutrient reference values in Australia and New Zealand recommend an upper limit of 50 mg a day in adults. "The same figure was set for pregnancy and lactation as there is no evidence of teratogenicity at this level. The UL was set based on metabolic body size and growth considerations for all other ages and life stages except infancy. It was not possible to set a UL for infants, so intake is recommended in the form of food, milk or formula." "The ULs were set using results of studies involving long-term oral administration of pyridoxine at doses of less than 1g/day (Berger & Schaumburg 1984, Bernstein & Lobitz 1988, Dalton 1985, Dalton & Dalton 1987, Del Tredici et al 1985, FNB:IOM 1998, Parry & Bredesen 1985). A NOAEL (No-observed-adverse-effect level) of 200 mg/day was identified from the studies of Bernstein & Lobitz (1988) and Del Tredici et al (1985). These studies involved subjects who had generally been on the supplements for five to six months or less. The study of Dalton and Dalton (1987), however, suggested the symptoms might take substantially longer than this to appear. In this latter retrospective survey, subjects who reported symptoms had been on supplements for 2.9 years, on average. Those reporting no symptoms had taken supplements for 1.9 years."[29]

Because no placebo-controlled studies show therapeutic benefits of high doses of pyridoxine, and the well-documented occurrence of significant toxic effects, there is little reason to exceed the RDI using supplements unless under medical supervision e.g. in treatment of primary hyperoxaluria.

Oncology[edit]

Vitamin B6 intake is inversely associated with the risk of colorectal cancer.[30]

Preventive roles and therapeutic uses[edit]

Vitamin B6 has been used to treat nausea and vomiting in early pregnancy for decades, commonly in conjunction with other medications such as metoclopramide or doxylamine. Alone, it has been found safe and effective, though any woman's prenatal caregiver must help guide treatment for these symptoms.[31]

At least one preliminary study has found this vitamin may increase dream vividness or the ability to recall dreams.[32] This effect is possibly due to the role this vitamin plays in the conversion of tryptophan to serotonin.[32] Anecdotal evidence suggests supplemental vitamin B6 may be associated with lucid dreaming.[citation needed]

The intake of vitamin B6, from either diet or supplements, could cut the risk of Parkinson's disease in smokers by half, according to a prospective study from the Netherlands.[33]

Pyridoxine has a role in preventing heart disease. Without enough pyridoxine, the compound homocysteine builds up in the body. Homocysteine damages blood vessel linings, setting the stage for plaque buildup when the body tries to heal the damage. Vitamin B6 prevents this buildup, thereby reducing the risk of heart attack. Pyridoxine lowers blood pressure and blood cholesterol levels and keeps blood platelets from sticking together. All of these properties work to keep heart disease at bay.[34][unreliable source?]

Nutritional supplementation with high dose vitamin B6 and magnesium is one of the most popular alternative medicine choices for autism, but randomised control trials have had mixed results and small sample sizes mean no conclusions can be drawn as to the efficacy of this treatment.[35][36]

Some studies suggest the vitamin B6-magnesium combination can also help attention deficit disorder, citing improvements in hyperactivity, hyperemotivity/aggressiveness and improved school attention.[37]

If people are marginally deficient in vitamin B6, they may be more susceptible to carpal tunnel syndrome (CTS). CTS is characterized by pain and tingling in the wrists after performing repetitive movements or otherwise straining the wrist regularly.[34] Vitamin B6 has been shown in at least two small-scale clinical studies[38][39] to have a beneficial effect on the syndrome, particularly in cases where no trauma or overuse etiology is known.

Vitamin B6 has long been publicized as a cure for premenstrual syndrome (PMS). Study results conflict as to which symptoms are eased, but most confirm women who take B6 supplements have reductions in bloating, breast pain, and premenstrual acne flare, a condition in which pimples break out about a week before a woman's period begins. Strong evidence suggests pyridoxine supplementation, starting 10 days before the menstrual period, prevents most pimples from forming. This effect is caused by the vitamin's role in hormone and prostaglandin regulation. Skin blemishes are typically caused by a hormone imbalance, which vitamin B6 helps to regulate.[34][unreliable source?]

Mental depression is another condition which may result from low vitamin B6 intake. Because of pyridoxine's role in serotonin and other neurotransmitter production, supplementation often helps depressed people feel better, and their moods improve significantly. It may also help improve memory in older adults.[34][unreliable source?] However, the effectiveness as treatment for PMS, PMDD, and clinical depression is debatable.[40][41]

Ingestion of vitamin B6 possibly can alleviate some of the many symptoms of an alcoholic hangover and morning sickness from pregnancy. This might result from its mild diuretic effect.[42] Though the mechanism is not known, results show pyridoxamine has therapeutic effects in clinical trials for diabetic nephropathy.[43]

Larsson et al. have shown vitamin B6 intake and pyridoxal phosphate (PLP) levels are inversely related to the risk of colon cancer. While in their study the correlation with B6 intake was moderate, it was quite dramatic with PLP levels, where the risk of colon cancer was decreased by nearly half.[44]

Vitamin B6 is also known to increase the metabolism of Parkinson's medications, such as levodopa,[citation needed] and should be used cautiously.

References[edit]

  1. ^ Paul Gyorgy (1934) "Vitamin B2 and the pellagra-like dermatitis in rats," Nature, vol. 133, pages 498–499.
  2. ^ György P, Eckardt RE (September 1940). "Further investigations on vitamin B(6) and related factors of the vitamin B(2) complex in rats. Parts I and II.". Biochem J. 34 (8–9): 1143–54. PMC 1265394. PMID 16747297. 
  3. ^ Enzyme Nomenclature
  4. ^ a b c d e f g h i j k l m n Combs, G.F. The Vitamins: Fundamental Aspects in Nutrition and Health. 2008. San Diego: Elsevier
  5. ^ Lichtstein HC, Gunsalus IC, Umbreit WW (1945). "Function of the vitamin B6 group; pyridoxal phosphate (codecarboxylase) in transamination" (PDF). J Biol Chem. 161 (1): 311–20. PMID 21005738. 
  6. ^ "Heme Synthesis". Rpi.edu. doi:10.1042/BJ20030513. Retrieved 2012-11-02. 
  7. ^ Food and Nutrition Board. Institute of Medicine. "Dietary Reference Intakes: Vitamins". National Academies, 2001.
  8. ^ http://www.iom.edu/~/media/Files/Activity%20Files/Nutrition/DRIs/DRI_Vitamins.ashx
  9. ^ McCormick, D. B. Vitamin B6 In: Present Knowledge in Nutrition (Bowman, B. A. and Russell, R. M., eds), 9th edition, vol. 2, p.270. Washington, D.C.: International Life Sciences Institute, 2006.
  10. ^ a b Sauberlich H. Vitamins -how much is for keeps? Nutr Today 1987; 22:20–28
  11. ^ Earl Mindell The Vitamin Bible, Arlington Books, 1982
  12. ^ "09038, Avocados, raw, California". National Nutrient Database for Standard Reference, Release 26. United States Department of Agriculture, Agricultural Research Service. Retrieved 14 August 2014. 
  13. ^ Andrews' Diseases of the Skin, 10th Edition, Elsevier.
  14. ^ Bowman, B.A., Russell, R. M. Present Knowledge in Nutrition. 9th Edition. Washington, DC: ILSI Press; 2006; pg.273
  15. ^ Rall L.C., Meydani S.N. (1993). "Vitamin B6 and immune competence". Nutrition Reviews 51 (8): 217–225. doi:10.1111/j.1753-4887.1993.tb03109.x. PMID 8302491. 
  16. ^ Massé, PG; Boudreau, J; Tranchant, CC; Ouellette, R; Ericson, KL (2012). "Type 1 diabetes impairs vitamin B(6) metabolism at an early stage of women's adulthood". Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme 37 (1): 167–75. doi:10.1139/h11-146. PMID 22288928. 
  17. ^ Bhagavan H.N. (1985). "Interraction between vitamin B6 and drugs". In Reynolds R.D., Leklem J.E. Vitamin B6: Its role in Health and Disease. New York: Liss. pp. 401–415. 
  18. ^ Gibson R.S. (2005). "Assessment of vitamin B6 status.". Principles of Nutritional Assessment (2nd ed.). New York: Oxford University Press. pp. 575–594. 
  19. ^ a b Liu A.,Lumeng L., Aronoff G., Li T-K. (1985). "Relationship between body store of vitamin B6 and plasma pyridoxal-P clearance: metabolic balance studies in humans". Journal of Laboratory and Clinical Medicine 106 (5): 491–497. PMID 4056565. 
  20. ^ Food and Nutrition Board Institute of Medicine (1998). Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, D.C.: National Academy Press. 
  21. ^ Leklem J (1990). "Vitamin B-6: A status report". J. Nutr 120: 1503–1507. PMID 2243296. 
  22. ^ Perry TA, Weerasuriya A, Mouton PR, Holloway HW, Greig NH. Pyridoxine-induced toxicity in rats: a stereological quantification of the sensory neuropathy. Exp Neurol2004, 190, 133–144
  23. ^ Schaumburg H, Kaplan J, Windebank A, Vick N, Rasmus S, Pleasure D, Brown MJ. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med 1983, 309, 445–448.
  24. ^ Foca FJ (September 1985). "Motor and sensory neuropathy secondary to excessive pyridoxine ingestion". Arch Phys Med Rehabil. 66 (9): 634–6. PMID 2994596. 
  25. ^ a b Katan MB (Nov 12, 2005). "[How much vitamin B6 is toxic?]". Ned Tijdschr Geneeskd. 149 (46): 2545–6. PMID 16320662. 
  26. ^ http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0404.1987.tb03536.x/abstract
  27. ^ Vitamin and Mineral Supplement Fact Sheets Vitamin B6
  28. ^ The EFSA Journal (2008) 760, 1–13
  29. ^ NHMRC Nutrient Reference Values - Nutrients vitamin B6
  30. ^ Larsson SC, Orsini N, Wolk A (March 2010). "Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective studies". JAMA 303 (11): 1077–83. doi:10.1001/jama.2010.263. PMID 20233826. 
  31. ^ Sheehan P. Hyperemesis gravidarum--assessment and management. Aust Fam Physician. 2007 Sep;36(9):698–701.
  32. ^ a b Ebben, M.; A Lequerica; A Spielman (2002). "Effects of Pyridoxine on Dreaming: a Preliminary Study". Perceptual and Motor Skills 94 (1): 135–40. doi:10.2466/pms.2002.94.1.135. PMID 11883552. Retrieved 2012-05-23. "The effect of pyridoxine (Vitamin B-6) on dreaming was investigated in a placebo, double-blind study to examine various claims that Vitamin B-6 increases dream vividness or the ability to recall dreams." 
  33. ^ "Increased intake of vitamin B6Sheet". Retrieved 2006-08-11. 
  34. ^ a b c d TLC Cooking "Benefits of Vitamin B6"
  35. ^ Pfeiffer SI, Norton J, Nelson L, Shott S (October 1995). "Efficacy of vitamin B6 and magnesium in the treatment of autism: a methodology review and summary of outcomes". Journal of Autism and Developmental Disorders 25 (5): 481–93. doi:10.1007/BF02178295. PMID 8567594. 
  36. ^ Angley M, Semple S, Hewton C, Paterson F, McKinnon R (2007). "Children and autism—part 2—management with complementary medicines and dietary interventions" (PDF). Aust Fam Physician 36 (10): 827–30. PMID 17925903. 
  37. ^ Mousain-Bosc M et al. (2006). "Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders". Magnesium Research 19 (1): 46–52. PMID 16846100. 
  38. ^ Ellis J et al. (Oct 1979). "Clinical results of a cross-over treatment with pyridoxine and placebo of the carpal tunnel syndrome". Am J Clin Nutr 32 (10): 2040–6. PMID 484522. 
  39. ^ Kasdan ML, Janes C.: Carpal tunnel syndrome and vitamin B6. Plast Reconstr Surg. 1987 Mar;79(3):456–62.
  40. ^ Vitamin Pills: Popping Too Many?, WebMD
  41. ^ "Vitamin B6 Therapy for PMDD", Complementary and Alternative Medicine, Creighton University School of Medicine
  42. ^ Ebbets, Russ. "The Mysterious Vitamin B6". USATF Niagara. Archived from the original on 2007-03-26. Retrieved 2012-05-14. 
  43. ^ Sergi V.C., Wenhui Zhang, Billy G.H., Anthony S.S., Paul A.V. Pyridoxamine protects proteins from functional damage by 3-Deoxyglucosone; mechanism of action of pyridoxamine. Biochemistry 2008, 47, 997–1006.
  44. ^ Larsson, S. et al. JAMA 2010; 303:1077–1083.

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