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Vitamin B₆

Vitamin B6 is one of the B-vitamins, used in producing a necessary coenzyme in the body. While essential and with many small benefits, there appear to be no highly effective unique reasons to use this supplement.

Our evidence-based analysis on vitamin b₆ features 69 unique references to scientific papers.

Research analysis led by and reviewed by the Examine team.
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Research Breakdown on Vitamin B₆

1Sources and Composition

1.1Origin and Composition

The term 'Vitamin B6' refers to a collection of molecules (vitamers) all sharing a structure similar to the pyridoxine molecule, possessing the form of pyridoxal 5'-phosphate (PLP) after ingestion which acts in the human body as an essential vitamin.

The role of PLP in the human body is mostly that of a coenzyme (similar to many essential minerals like zinc), being required in sufficient amounts to allow proper functioning of certain enzymes.[2] The enzymes that PLP helps function are mostly involved in cellular proliferation and regulation[3] while low serum vitamin B6 status seems to be correlated with a few cancerous states (abnormalities in cellular proliferation and regulation).[4][5][6][7]

1.2Sources and Structure

Dietary forms of vitamin B6 include:

  • Pyridoxine

  • Pyridoxal

  • Pyridoxamine

1.3Biological Significance

After intestinal absorption, these dietary/supplemental forms of B6 which are considered inactive are converted into the bioactive pyridoxal 5'-phosphate (PLP) in the liver[8] and intestines themselves[9] and then bound to serum albumin[10] to be transported to peripheral tissue.

All three major dietary forms of vitamin B6 (pyridoxine, pyridoxal, and pyridoxamine) are initially subject to the enzyme pyridoxal kinase[11] which adds a phosphate group at the 5' position, although only in the case of pyridoxal does this process form PLP; the product of pyridoxine (pyridoxine 5'-phosphate) and that of pyrixodamine (pyridoxamine 5'-phosphate) both need to be additionally subject to the enzyme pyridox(am)ine phosphate oxidase to finally produce PLP.[12]

PLP can be hydrolyzed back into pyridoxal via PLP phosphatase, and this enzyme can also work on pyridoxine-5'-phosphate to convert it back into pyridoxine.[13] This must occur for pyridoxal to be subject to aldehyde oxidase to produce the urinary metabolite 4-pyridoxic acid (4-PA) which is the end product of vitamin B6 metabolism.



It was initially thought that intestinal uptake of vitamin B6 as pyridoxine hydrochloride,[14][15] pyridoxal (including its phosphate form[16]), and pyridoxamine (as well as its phosphate[17]) were via passive diffusion in the rat.

Human studies on isolated intestinal cells (Caco-2) have noted a saturatable transporter which is concentration and pH dependent, capable of absorbing PLP and pyridoxamine;[18] this is in contrast to a colonic transporter which which does not uptake PLP[19] and neither transporter appears to be capable of uptaking pyridoxamine.[18][19]

Mechanistically, there appear to be transporters for vitamin B6 vitamers which absorb pyridoxamine; in the jejunem (main site of absorption in the intestines) pyridoxal-5'-phosphate may also be absorbed

When tested in situ with jejunal segments, it was noted that while a few fiber types (cellulose, pectin, and lignan) did not influence absorption rates while homogenized carrots at 1-3% of the medium reduced the absorption of pyridoxamine and pyridoxal but not pyridoxine.[20] This may be related to how a synthetic solution of pyridoxine is more bioavailable than a similar dose via orange juice,[21] even though adding sugar to the synthetic solution enhances bioavailability (via intrajejunal infusion).[21]


3.1Dopaminergic Neurotransmission

The enzyme that converts L-DOPA into active dopamine, L-dopa decarboxylase, is a pyridoxine-5'-phosphate (PLP) dependent enzyme[22] and due to the actions of pyridoxine infusion paralelling that of dopamine (in regards to prolactin and growth hormone) it is thought that additional pyridoxine increases the activity of this enzyme particularly in the hypothalamus.[23] It is known that a deficiency of PLP hinders the activity of this enzyme in the brain.[24] 

3.2Serotonergic Neurotransmission

Rats deficient in pyridoxine have significantly reduced hypothalamic levels of both pyridoxal phosphate (PLP) and serotonin, which seem to result in low plasma prolactin levels; since the plasma prolactin was remedied with a 5-HT1A agonist, it was thought that a deficiency in pyridoxine reduces activity of this serotonin receptor in the hypothalamus.[25]

3.3Hallucination and Euphoria

Pyridoxine has been suggested to be a contributor to inducing dreams due to its interaction with l-dopa decarboxylase crossing over into dopamine and serotonin production. Serotonin based drugs (such as SSRIs) have been noted to increase subjective dream intensity[26] and it is hypothesized that increased arousal during REM sleep (when dreaming appears to occur most frequently) and subsequent waking may underlie the increases in dream intensity and frequency reported with pyridoxine.

When testing dream salience (subjective intensity of a dream) as self-reported after a night of sleep, 100mg and 250mg pyridoxine showed dose-dependent increases in dream salience relative to placebo.[27]

4Obesity and Fat Mass


Increasing the pyridoxal-5'-phosphate (PLP) content of 3T3-L1 adipocytes to the range of 50-100nM appears to dose-dependently reduce intracellular calcium in the range of 12-36% with a similar reduction in fatty acid synthase (FAS) activity and expression.[1] This is thought to be a result of pyridoxine's negative regulation of calcium signalling in general[28] and the adipogenic actions of calcium in body fat tissue.[29][30]


Supplementation of a combination of leucine (2.25g) with pyridoxine (30mg) in overweight persons has been noted to reduce the respiratory exchange ratio by 0.019 units (calculated to increase fat loss by 33.6g daily) relative to placebo.[1]

5Interactions with Hormones


Transcriptional activity of glucocorticoid receptors seems to be inversely related to cellular concentrations of pyridoxal 5'-phosphate (PLP) with higher concentrations suppressing activity.[31][32] Mimicking a mild deficiency (adding no pyridoxine to medium) can increase activity of the receptor 98% whereas elevating PLP (1,000µM) can suppress activity 48%.[33]

One study using 200mg pyridoxine twice daily in 10 otherwise healthy women failed to note any changes in cortisol or ACTH relative to baseline.[34]

5.2Growth Hormones

While 1,000μM of bioactive pyridoxine is able to inhibit growth hormone secretion from pituitary cells, lower concentrations of 1-100μM in primary rat pituitary cells have failed to have an effect.[35]

Supplementation of pyridoxine in otherwise healthy women acutely (200mg twice daily) failed to significantly increase growth hormone secretion over 24 hours, causing a nonsignificant trend to increase nighttime growth hormone.[34]

During physical exercise with an infusion of 600mg pyridoxine administration of the drug was associated with a larger increase in growth hormone levels in serum during a cycling test, although control appeared to have slightly lower serum pyridoxine at baseline[36] and a lower dosed infusion of 300mg has been noted elsewhere to increase growth hormone in hospitalized persons acutely.[23]


In rats, a deficiency of vitamin B6 results in an increase in plasma prolactin concentration.[25]

Pyridoxal phosphate (PLP) is able to inhibit pituitary cell proliferation in vitro in various cell lines (MMQ, AtT-20, GH3) between 10-1,000μM not associated with toxicity and in a reversible manner after PLP removal,[35] this reduction in proliferation being associated with less hormone secretion and in primary rat pituitary cells 1μM is able to suppress prolactin secretion to 66% of control (48% at 10μM) without affecting growth hormone.[35]

Vitamin B6 appears to have a generally suppressive effect on prolactin, with a deficiency in B6 causing higher than normal serum B6 concentrations and increasing concentrations causing further suppressions of prolactin

A suppression of prolactin increases have been noted in various rodent studies with infusions of pyridoxine, including a hindering of a chlorpromazine[37] and opioid[38] induced prolactin spike.

There may be a slight suppression of prolactin concentrations acutely in women given 200mg pyridoxine twice daily when measuring blood over the course of 24 hours, relative to baseline values.[34]

The increase in prolactin seen during exercise has been noted to be fully abrogated with continuous infusion of 600mg pyridoxine.[36]

6Interactions with Cancer Metabolism

6.1Breast Cancer

When assessing plasma pyridoxal-5'-phosphate (PLP) concentration in menopausal women, serum PLP appeared to be inversely associated with breast cancer risk when assessing prediagnostic values as the highest quartile (greater than 116.6nM) had 30% less risk than the lowest quartile (less than 41.1nM).[39]

6.2Adjuvant Usage

Hand-foot syndrome (HFS), a reddening of the hands and soles of the feet commonly seen with usage of the chemotherapeutic capecitabine,[40] has traditionally been claimed to reduce these symptoms with mixed results. This traditional usage arose due to the visual similarities between HFS and rat acrodynia caused by pyridoxine deficiency[41] and due to a pilot study where four out of five persons given 50-150mg pyridoxine after HFS developed (from intravenous 5-fluorouracil) found benefits to symptoms.[42]

50mg pyridoxine thrice daily over 12 weeks (150mg each day) in persons with breast or colon cancer on capecitabine therapy failed to significantly reduce symptoms incidence, severity, or dose modification of capecitabine due to symptoms relative to placebo;[43] there were some positive trends that failed to reach significance most notable for symptom severity, and pyridoxine had no influence on cancer outcomes.[43]

7Nutrient-Nutrient Interactions

7.1COX Inhibitors

COX inhibitors are a class of antiinflammatory drugs of which include NSAIDs like aspirin.

It appears that in a cohort of persons using NSAIDs relative to those not on the drugs, those using NSAIDs have a lower concentration of bioactive B6 (pyridoxal-5'-phosphate) which was time dependent with larger decreases seen with longer drug usage;[44] decreases in liver and kidney PLP concentration was noted in rats and mice on NSAIDs for prolonged periods of time.[44]


ZMA is a formulation named after the acronym of Zinc and Magnesium (as Aspartate chelate) but routinely includes the addition of vitamin B6.

The inherent 5α-reductase inhibitory effect of zinc (which would increase testosterone via reducing its conversion into the androgen DHT) occurs at too high a concentration to be relevant to supplementation at 15mM in vitro, and the addition of high concentrations of pyridoxine appear to reduce the required amount of zinc for this effect down to 1.5-3mM.[45] This information is still not thought to apply to dietary supplementation, since zinc is associated with an increase in DHT after supplementation[46] which occurs at the level of the 5α-reductase enzyme at 500nM (0.5µM).[47]

8Safety and Toxicology

8.1Pyridoxine Neuropathy

Pyridoxine neuropathy refers to a particular form of neuropathy (nerve damage) where high doses of any vitamin B6 vitamer can, over time, cause adverse symptoms[48] mostly characterized in humans when doses exceeding 6,000mg are taken for longer than one year with the primary symptoms of sensory ataxia, diminished distal limb proprioception, paresthesia, and hyperesthesia.[48][49][50] 

At least one study noted a case where some adverse effects were noted at as little as 200mg (11,700% the RDI and 200% the TUL)[51] although most dog studies where neuropathy is successfully replicated have used 50-300mg/kg[52][53][54] (estimated human range of 27-162mg/kg and, for a 150lb person, at least 1.8g; similar estimated ranges from rat data[55][56]). Toxicity can be exerted in as little as 1-15 days in rats, although it requires 600-1,200mg/kg via intraperitoneal infusion.[56][57][58]

There also appear to be two toxic 'levels', with the lower dose being an axonopathy (destruction of axons) which appears to be reversible upon pyridoxine discontinuation and the higher level being an irreversible sensory ganglion neuropathy.[56][59]

Vitamin B6 is known to be highly toxic when megadosed for a prolonged period of time, at best causing peripheral neuropathy that can be repairable and at worst causing irreversible sensory ganglion neuropathy. The lowest estimate this toxic dose has been reported is at 200mg (11,700% the RDI) while it is reliable induced at around 5g (300,000% the RDI) or higher intake in humans


  1. ^ a b c Zemel MB1, Bruckbauer A. Effects of a leucine and pyridoxine-containing nutraceutical on fat oxidation, and oxidative and inflammatory stress in overweight and obese subjects. Nutrients. (2012)
  2. ^ Clayton PT. B6-responsive disorders: a model of vitamin dependency. J Inherit Metab Dis. (2006)
  3. ^ Allgood VE1, Cidlowski JA. Vitamin B6 modulates transcriptional activation by multiple members of the steroid hormone receptor superfamily. J Biol Chem. (1992)
  4. ^ Zhang SM1, et al. Plasma folate, vitamin B6, vitamin B12, homocysteine, and risk of breast cancer. J Natl Cancer Inst. (2003)
  5. ^ Wei EK1, et al. Plasma vitamin B6 and the risk of colorectal cancer and adenoma in women. J Natl Cancer Inst. (2005)
  6. ^ Kamat AM1, Lamm DL. Chemoprevention of bladder cancer. Urol Clin North Am. (2002)
  7. ^ Bidoli E1, et al. Micronutrients and laryngeal cancer risk in Italy and Switzerland: a case-control study. Cancer Causes Control. (2003)
  8. ^ Merrill AH Jr1, Henderson JM. Vitamin B6 metabolism by human liver. Ann N Y Acad Sci. (1990)
  9. ^ Albersen M1, et al. The intestine plays a substantial role in human vitamin B6 metabolism: a Caco-2 cell model. PLoS One. (2013)
  10. ^ Fonda ML1, Trauss C, Guempel UM. The binding of pyridoxal 5'-phosphate to human serum albumin. Arch Biochem Biophys. (1991)
  11. ^ Pyridoxal Phosphokinases: I. Assay, Distribution, Purification, and Properties.
  12. ^ Ngo EO1, et al. Absence of pyridoxine-5'-phosphate oxidase (PNPO) activity in neoplastic cells: isolation, characterization, and expression of PNPO cDNA. Biochemistry. (1998)
  13. ^ Jang YM1, et al. Human pyridoxal phosphatase. Molecular cloning, functional expression, and tissue distribution. J Biol Chem. (2003)
  14. ^ Middleton HM 3rd. Uptake of pyridoxine hydrochloride by the rat jejunal mucosa in vitro. J Nutr. (1977)
  15. ^ BOOTH CC, BRAIN MC. The absorption of tritium-labelled pyridoxine hydrochloride in the rat. J Physiol. (1962)
  16. ^ Mehansho H, Hamm MW, Henderson LM. Transport and metabolism of pyridoxal and pyridoxal phosphate in the small intestine of the rat. J Nutr. (1979)
  17. ^ Hamm MW, Mehansho H, Henderson LM. Transport and metabolism of pyridoxamine and pyridoxamine phosphate in the small intestine of the rat. J Nutr. (1979)
  18. ^ a b Said HM1, Ortiz A, Ma TY. A carrier-mediated mechanism for pyridoxine uptake by human intestinal epithelial Caco-2 cells: regulation by a PKA-mediated pathway. Am J Physiol Cell Physiol. (2003)
  19. ^ a b Said ZM1, et al. Pyridoxine uptake by colonocytes: a specific and regulated carrier-mediated process. Am J Physiol Cell Physiol. (2008)
  20. ^ Nguyen LB, Gregory JF 3rd, Cerda JJ. Effect of dietary fiber on absorption of B-6 vitamers in a rat jejunal perfusion study. Proc Soc Exp Biol Med. (1983)
  21. ^ a b Nelson EW Jr, Lane H, Cerda JJ. Comparative human intestinal bioavailability of vitamin B-6 from a synthetic and a natural source. J Nutr. (1976)
  22. ^ Mappouras DG1, Stiakakis J, Fragoulis EG. Purification and characterization of L-dopa decarboxylase from human kidney. Mol Cell Biochem. (1990)
  23. ^ a b Delitala G, et al. Effect of pyridoxine on human hypophyseal trophic hormone release: a possible stimulation of hypothalamic dopaminergic pathway. J Clin Endocrinol Metab. (1976)
  24. ^ Allen GF1, et al. Pyridoxal 5'-phosphate deficiency causes a loss of aromatic L-amino acid decarboxylase in patients and human neuroblastoma cells, implications for aromatic L-amino acid decarboxylase and vitamin B(6) deficiency states. J Neurochem. (2010)
  25. ^ a b Sharma SK1, Dakshinamurti K. Effects of serotonergic agents on plasma prolactin levels in pyridoxine-deficient adult male rats. Neurochem Res. (1994)
  26. ^ Pace-Schott EF1, et al. SSRI treatment suppresses dream recall frequency but increases subjective dream intensity in normal subjects. J Sleep Res. (2001)
  27. ^ Ebben M1, Lequerica A, Spielman A. Effects of pyridoxine on dreaming: a preliminary study. Percept Mot Skills. (2002)
  28. ^ Dakshinamurti K1, Lal KJ, Ganguly PK. Hypertension, calcium channel and pyridoxine (vitamin B6). Mol Cell Biochem. (1998)
  29. ^ Villarroel P1, et al. Adipogenic effect of calcium sensing receptor activation. Mol Cell Biochem. (2013)
  30. ^ He YH1, et al. The calcium-sensing receptor promotes adipocyte differentiation and adipogenesis through PPARγ pathway. Mol Cell Biochem. (2012)
  31. ^ Allgood VE1, Powell-Oliver FE, Cidlowski JA. The influence of vitamin B6 on the structure and function of the glucocorticoid receptor. Ann N Y Acad Sci. (1990)
  32. ^ Allgood VE1, Powell-Oliver FE, Cidlowski JA. Vitamin B6 influences glucocorticoid receptor-dependent gene expression. J Biol Chem. (1990)
  33. ^ Allgood VE1, Oakley RH, Cidlowski JA. Modulation by vitamin B6 of glucocorticoid receptor-mediated gene expression requires transcription factors in addition to the glucocorticoid receptor. J Biol Chem. (1993)
  34. ^ a b c Barletta C, et al. Influence of administration of pyridoxine on circadian rhythm of plasma ACTH, cortisol prolactin and somatotropin in normal subjects. Boll Soc Ital Biol Sper. (1984)
  35. ^ a b c Ren SG1, Melmed S. Pyridoxal phosphate inhibits pituitary cell proliferation and hormone secretion. Endocrinology. (2006)
  36. ^ a b Moretti C, et al. Pyridoxine (B6) suppresses the rise in prolactin and increases the rise in growth hormone induced by exercise. N Engl J Med. (1982)
  37. ^ Rosenberg JM, Lau-Cam CA, McGuire H. Effects of pyridoxine hydrochloride (vitamin B6) on chlorpromazine-induced serum prolactin rise in male rats. J Pharm Sci. (1979)
  38. ^ Vescovi PP, et al. Pyridoxine (Vit. B6) decreases opioids-induced hyperprolactinemia. Horm Metab Res. (1985)
  39. ^ Lurie G1, et al. Prediagnostic plasma pyridoxal 5'-phosphate (vitamin b6) levels and invasive breast carcinoma risk: the multiethnic cohort. Cancer Epidemiol Biomarkers Prev. (2012)
  40. ^ Gressett SM1, Stanford BL, Hardwicke F. Management of hand-foot syndrome induced by capecitabine. J Oncol Pharm Pract. (2006)
  41. ^ Vukelja SJ, et al. Pyridoxine for the palmar-plantar erythrodysesthesia syndrome. Ann Intern Med. (1989)
  42. ^ Fabian CJ1, et al. Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with continuous 5-fluorouracil infusion. Invest New Drugs. (1990)
  43. ^ a b Corrie PG1, et al. A randomised study evaluating the use of pyridoxine to avoid capecitabine dose modifications. Br J Cancer. (2012)
  44. ^ a b Chang HY1, et al. Clinical use of cyclooxygenase inhibitors impairs vitamin B-6 metabolism. Am J Clin Nutr. (2013)
  45. ^ Stamatiadis D, Bulteau-Portois MC, Mowszowicz I. Inhibition of 5 alpha-reductase activity in human skin by zinc and azelaic acid. Br J Dermatol. (1988)
  46. ^ Netter A, Hartoma R, Nahoul K. Effect of zinc administration on plasma testosterone, dihydrotestosterone, and sperm count. Arch Androl. (1981)
  47. ^ Leake A, Chisholm GD, Habib FK. The effect of zinc on the 5 alpha-reduction of testosterone by the hyperplastic human prostate gland. J Steroid Biochem. (1984)
  48. ^ a b Schaumburg H, et al. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med. (1983)
  49. ^ Foca FJ. Motor and sensory neuropathy secondary to excessive pyridoxine ingestion. Arch Phys Med Rehabil. (1985)
  50. ^ Dalton K, Dalton MJ. Characteristics of pyridoxine overdose neuropathy syndrome. Acta Neurol Scand. (1987)
  51. ^ Parry GJ, Bredesen DE. Sensory neuropathy with low-dose pyridoxine. Neurology. (1985)
  52. ^ Montpetit VJ1, et al. Alteration of neuronal cytoskeletal organization in dorsal root ganglia associated with pyridoxine neurotoxicity. Acta Neuropathol. (1988)
  53. ^ Krinke G1, et al. Pyridoxine megavitaminosis produces degeneration of peripheral sensory neurons (sensory neuronopathy) in the dog. Neurotoxicology. (1981)
  54. ^ Hoover DM, Carlton WW, Henrikson CK. Ultrastructural lesions of pyridoxine toxicity in beagle dogs. Vet Pathol. (1981)
  55. ^ Windebank AJ, et al. Pyridoxine neuropathy in rats: specific degeneration of sensory axons. Neurology. (1985)
  56. ^ a b c Krinke GJ1, Fitzgerald RE. The pattern of pyridoxine-induced lesion: difference between the high and the low toxic level. Toxicology. (1988)
  57. ^ Xu Y1, Sladky JT, Brown MJ. Dose-dependent expression of neuronopathy after experimental pyridoxine intoxication. Neurology. (1989)
  58. ^ Krinke G, Naylor DC, Skorpil V. Pyridoxine megavitaminosis: an analysis of the early changes induced with massive doses of vitamin B6 in rat primary sensory neurons. J Neuropathol Exp Neurol. (1985)
  59. ^ Perry TA1, et al. Pyridoxine-induced toxicity in rats: a stereological quantification of the sensory neuropathy. Exp Neurol. (2004)
  60. Masoumi SZ, Ataollahi M, Oshvandi K. Effect of Combined Use of Calcium and Vitamin B6 on Premenstrual Syndrome Symptoms: a Randomized Clinical Trial. J Caring Sci. (2016)
  61. Ebrahimi E, et al. Effects of magnesium and vitamin b6 on the severity of premenstrual syndrome symptoms. J Caring Sci. (2012)
  62. Kashanian M, Mazinani R, Jalalmanesh S. Pyridoxine (vitamin B6) therapy for premenstrual syndrome. Int J Gynaecol Obstet. (2007)
  63. De Souza MC, et al. A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study. J Womens Health Gend Based Med. (2000)
  64. Doll H, et al. Pyridoxine (vitamin B6) and the premenstrual syndrome: a randomized crossover trial. J R Coll Gen Pract. (1989)
  65. Kendall KE, Schnurr PP. The effects of vitamin B6 supplementation on premenstrual symptoms. Obstet Gynecol. (1987)
  66. Hagen I, Nesheim BI, Tuntland T. No effect of vitamin B-6 against premenstrual tension. A controlled clinical study. Acta Obstet Gynecol Scand. (1985)
  67. Williams MJ, Harris RI, Dean BC. Controlled trial of pyridoxine in the premenstrual syndrome. J Int Med Res. (1985)
  68. Shobeiri F, Oshvandi K, Nazari M. Clinical effectiveness of vitamin E and vitamin B6 for improving pain severity in cyclic mastalgia. Iran J Nurs Midwifery Res. (2015)
  69. Lauritzen C, et al. Treatment of premenstrual tension syndrome with Vitex agnus castus controlled, double-blind study versus pyridoxine. Phytomedicine. (1997)