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What is it?


Vitamin B6 (pyridoxine) is an essential water-soluble vitamin. It acts as a coenzyme in more than 140 biochemical reactions involving carbohydrates, lipids, proteins, and amino acids, and it helps to produce neurotransmitters, glycogen, and glucose. Its three natural forms,  pyridoxine, pyridoxal, and pyridoxamine, are converted to the active coenzyme pyridoxal-5-phosphate (PLP or P5P) when consumed. (1)(43) Each of the natural forms have a 5-phosphate form. (36) Pyridoxal-5-phosphate is the main active metabolite that is often measured to determine whether an individual’s vitamin B6 levels are suboptimal (20-30 nmol/L) or deficient (<20 nmol/L). Low levels of B6 are correlated with various chronic diseases, including cardiovascular disease, stroke, diabetes, or cancer. In supplemental forms, vitamin B6 is regularly combined with other B vitamins such as vitamin B12 (cobalamin) and vitamin B9 (folic acid) to improve efficacy. (55)

It is important to note that while vitamin B6 has been widely studied in combination with other B vitamins, only the studies that show its efficacy as an isolated ingredient are provided in this review.

Main uses

Nausea and vomiting
Neurological function
Premenstrual syndrome


Pyridoxine hydrochloride (HCl)
Most widely used form in dietary supplements and clinical trials
Pyridoxal-5- phosphate (P5P)
Commonly used in supplements as it is the active form of vitamin B6
Though P5P is the bioactive form, intestinal absorption requires orally ingested P5P to be dephosphorylated, which likely reduces bioavailability relative to its non-phosphorylated forms (i.e., pyridoxine, pyridoxal, or pyridoxamine). (18)
Supplementation with intravenous P5P may be required to raise P5P in patients with liver dysfunction since it does not require hepatocytes to metabolize B6 vitamers to P5P. (27)
Similar applications as above may be required for individuals with disorders that limit B6 metabolism. For example, genetic mutations can reduce the production of intracellular P5P by inhibiting enzymatic conversion of B6 vitamers (i.e., pyridoxine, pyridoxal, or pyridoxamine) to P5P, causing B6 deficiency. Deficiencies may manifest as clinical features including seizures as observed in PLP-dependent epilepsy. (60)
Pyridoxamine dihydrochloride (2HCl)
A B6 therapy which was particularly studied to reduce advanced glycation end products (AGEs) in diabetic nephropathy
However, since the FDA accepted pyridoxamine as the active ingredient in an investigational pharmaceutical product in 2009, it has not been legally classified to meet the definition of a dietary supplement. (57)

Dosing & administration

Adverse effects

According to cohort studies and randomized controlled trials, vitamin B6 does not appear to increase the prevalence of adverse events compared to control groups within dose ranges up to 230 mg per day. Case series and case reports indicate that high doses may cause numbness or peripheral neuropathy. (10) More than 1,000 mg per day may be required to cause neuropathy; however, some cases have been reported after taking up to 500 mg per day for several months. (21)

Overall, there is little evidence of the induction neuropathy when used at doses lower than 100 mg for up to 30 weeks, though other possible adverse effects include indigestion and nausea, light sensitivity, and breast tenderness. (1) Other side effects may include the inhibition of platelet aggregation, (49) as well as the impairment of semen quality parameters (as shown in rodents), but this needs to be confirmed in humans. (7) It may be noted that vitamin B6 intake of more than 50 mg per day may be more likely to result in clinically significant drug interactions, such as with levodopa. (48

Some in vitro evidence suggests that long-term high dosing with pyridoxine may not be as safe as P5P or other forms since pyridoxine may competitively inhibit enzymatic conversion of B6 vitamers to P5P. Bioaccumulation of pyridoxine may thereby lead (contradictorily) to polyneuropathy (an adverse event observed in B6 deficiency) induced by cellular death, an observation not recorded with other B6 forms. (59)



  • Vitamin B6 is absorbed in the upper intestinal tract by passive diffusion, though in vitro evidence for selective transporter proteins for B6 vitamers is emerging. (3)
  • Phosphorylated B6 vitamers must be dephosphorylated prior to intestinal absorption and their release to the hepatic portal system for further metabolism to P5P. (3)


  • Once absorbed, B6 is metabolized to P5P and is widely circulated throughout the body bound to albumin. (63)
  • To be absorbed into cells, P5P is dephosphorylated to pyridoxal before being re-phosphorylated back into its active coenzyme form intracellularly. (3)


  • Vitamin B6 forms are converted to the active coenzyme (P5P) and 4-pyridoxic acid (4-PA) in the liver. (3)(38)


  • B6 derivatives are excreted in the urine, primarily as 4-PA. (3)(9)(61)(63)
  • The approximate half-lives of orally administered pyridoxine and P5P is 1.3 hours and 2.3 hours, respectively. (63)
  1. Abosamak, N. E. R., & Gupta, V. (2020). Vitamin B6 (Pyridoxine). In StatPearls. StatPearls Publishing. 
  2. Adelufosi, A. O., Abayomi, O., & Ojo, T. M.-F. (2015). Pyridoxal 5 phosphate for neuroleptic-induced tardive dyskinesia. Cochrane Database of Systematic Reviews, 4, CD010501. 
  3. Albersen, M., Bosma, M., Knoers, N. V. V. A. M., de Ruiter, B. H. B., Diekman, E. F., de Ruijter, J., Visser, W. F., de Koning, T. J., & Verhoeven-Duif, N. M. (2013). The intestine plays a substantial role in human vitamin B6 metabolism: A Caco-2 cell model. PloS One, 8(1), e54113. 
  4. Artukoglu, B. B., Li, F., Szejko, N., & Bloch, M. H. (2020). Pharmacologic treatment of tardive dyskinesia: A meta-analysis and systematic review. The Journal of Clinical Psychiatry, 81(4). 
  5. Aybak, M., Sermet, A., Ayyildiz, M. O., & Karakilçik, A. Z. (1995). Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension. Arzneimittel-Forschung, 45(12), 1271–1273. 
  6. Balk, E. M., Raman, G., Tatsioni, A., Chung, M., Lau, J., & Rosenberg, I. H. (2007). Vitamin B6, B12, and folic acid supplementation and cognitive function: A systematic review of randomized trials. Archives of Internal Medicine, 167(1), 21–30. 
  7. Banihani, S. A. (2017). A systematic review evaluating the effect of vitamin B6 on semen quality. Urology Journal, 15(1), 1–5. 
  8. Behrens, A., Graessel, E., Pendergrass, A., & Donath, C. (2020). Vitamin B-Can it prevent cognitive decline? A systematic review and meta-analysis. Systematic Reviews, 9(1), 111. 
  9. Bor, M. V., Refsum, H., Bisp, M. R., Bleie, Ø., Schneede, J., Nordrehaug, J. E., Ueland, P. M., Nygard, O. K., & Nexø, E. (2003). Plasma vitamin B6 vitamers before and after oral vitamin B6 treatment: A randomized placebo-controlled study. Clinical Chemistry, 49(1), 155–161. 
  10. Chen, M., Zhang, L.-L., Quan, S. Y. I., & Hu, Z.-Q. (2016). Safety of medication of vitamin B6: A systematic review. Chinese Pharmaceutical Journal, 51(1), 65–69. 
  11. Cheng, S.-B., Lin, P.-T., Liu, H.-T., Peng, Y.-S., Huang, S.-C., & Huang, Y.-C. (2016). Vitamin B-6 supplementation could mediate antioxidant capacity by reducing plasma homocysteine concentration in patients with hepatocellular carcinoma after tumor resection. BioMed Research International, 2016, 7658981. 
  12. Chittumma, P., Kaewkiattikun, K., & Wiriyasiriwach, B. (2007). Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: A randomized double-blind controlled trial. Journal of the Medical Association of Thailand, 90(1), 15–20. 
  13. Corken, M., & Porter, J. (2011). Is vitamin B(6) deficiency an under-recognized risk in patients receiving haemodialysis? A systematic review: 2000-2010. Nephrology , 16(7), 619–625. 
  14. Deijen, J. B., van der Beek, E. J., Orlebeke, J. F., & van den Berg, H. (1992). Vitamin B-6 supplementation in elderly men: Effects on mood, memory, performance and mental effort. Psychopharmacology, 109(4), 489–496. 
  15. Di Comite, A., Esposito, S., Villani, A., Stronati, M., & Italian Pediatric TB Study Group. (2016). How to manage neonatal tuberculosis. Journal of Perinatology, 36(2), 80–85. 
  16. Doll, H., Brown, S., Thurston, A., & Vessey, M. (1989). Pyridoxine (vitamin B6) and the premenstrual syndrome: A randomized crossover trial. The Journal of the Royal College of General Practitioners, 39(326), 364–368. 
  17. Ebrahimi, E., Khayati Motlagh, S., Nemati, S., & Tavakoli, Z. (2012). Effects of magnesium and vitamin B6 on the severity of premenstrual syndrome symptoms. Journal of Caring Sciences, 1(4), 183–189. 
  18. European Food Safety Authority (EFSA). (2008). Opinion on Pyridoxal 5’‐phosphate as a source for vitamin B6 added for nutritional purposes in food supplements ‐ Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food. EFSA Journal, 6(7). 
  19. Ford, A. H., & Almeida, O. P. (2012). Effect of homocysteine lowering treatment on cognitive function: A systematic review and meta-analysis of randomized controlled trials. Journal of Alzheimer’s Disease, 29(1), 133–149. 
  20. Gregory, J. F., 3rd. (2012). Accounting for differences in the bioactivity and bioavailability of vitamers. Food & Nutrition Research, 56. 
  21. Hemminger, A., & Wills, B. K. (2020). Vitamin B6 Toxicity. In StatPearls. StatPearls Publishing. 
  22. Hillman, R. W., Cabaud, P. G., Nilsson, D. E., Arpin, P. D., & Tufano, R. J. (1963). Pyridoxine supplementation during pregnancy. Clinical and laboratory observations. The American Journal of Clinical Nutrition, 12(6), 427–430. 
  23. Hlais, S., Reslan, D. R. A., Sarieddine, H. K., Nasreddine, L., Taan, G., Azar, S., & Obeid, O. A. (2012). Effect of lysine, vitamin B(6), and carnitine supplementation on the lipid profile of male patients with hypertriglyceridemia: A 12-week, open-label, randomized, placebo-controlled trial. Clinical Therapeutics, 34(8), 1674–1682. 
  24. Jiao, F. Y., Gao, D. Y., Takuma, Y., Wu, S., Liu, Z. Y., Zhang, X. K., Lieu, N. S., Ge, Z. L., Chui, W., Li, H. R., Cao, Y. M., Bai, A. N., & Liu, S. B. (1997). Randomized, controlled trial of high-dose intravenous pyridoxine in the treatment of recurrent seizures in children. Pediatric Neurology, 17(1), 54–57. 
  25. Kashanian, M., Mazinani, R., Jalalmanesh, S., & Babayanzad Ahari, S. (2007). Pyridoxine (vitamin B6) therapy for premenstrual syndrome. International Journal of Gynaecology and Obstetrics, 96(1), 43–44. 
  26. Kendall, K. E., & Schnurr, P. P. (1987). The effects of vitamin B6 supplementation on premenstrual symptoms. Obstetrics and Gynecology, 70(2), 145–149. 
  27. Labadarios, D., Rossouw, J. E., McConnell, J. B., Davis, M., & Williams, R. (1977). Vitamin B6 deficiency in chronic liver disease--evidence for increased degradation of pyridoxal-5’-phosphate. Gut, 18(1), 23–27. 
  28. Lauritzen, C., Reuter, H. D., Repges, R., Böhnert, K. J., & Schmidt, U. (1997). Treatment of premenstrual tension syndrome with Vitex agnus castus controlled, double-blind study versus pyridoxine. Phytomedicine, 4(3), 183–189. 
  29. Lerner, V., Bergman, J., Statsenko, N., & Miodownik, C. (2004). Vitamin B6 treatment in acute neuroleptic-induced akathisia: A randomized, double-blind, placebo-controlled study. The Journal of Clinical Psychiatry, 65(11), 1550–1554. 
  30. Lerner, V., Miodownik, C., Kaptsan, A., Bersudsky, Y., Libov, I., Sela, B.-A., & Witztum, E. (2007). Vitamin B6 treatment for tardive dyskinesia: A randomized, double-blind, placebo-controlled, crossover study. The Journal of Clinical Psychiatry, 68(11), 1648–1654. 
  31. Lerner, V., Miodownik, C., Kaptsan, A., Cohen, H., Matar, M., Loewenthal, U., & Kotler, M. (2001). Vitamin B(6) in the treatment of tardive dyskinesia: A double-blind, placebo-controlled, crossover study. The American Journal of Psychiatry, 158(9), 1511–1514. 
  32. Liampas, I. N., Siokas, V., Aloizou, A.-M., Tsouris, Z., Dastamani, M., Aslanidou, P., Brotis, A., & Dardiotis, E. (2020). Pyridoxine, folate and cobalamin for migraine: A systematic review. Acta Neurologica Scandinavica, 142(2), 108–120. 
  33. Malouf, R., & Grimley Evans, J. (2003). The effect of vitamin B6 on cognition. Cochrane Database of Systematic Reviews , 4, CD004393. 
  34. Mandana, Z., & Azar, A. (2013). Comparison of the effect of vit E, vit B6, calcium and omega-3 on the treatment of premenstrual syndrome: A clinical randomized trial. Annual Research & Review in Biology, 4(7), 1141–1149. 
  35. Marino, S., Vitaliti, G., Marino, S. D., Pavone, P., Provvidenti, S., Romano, C., & Falsaperla, R. (2018). Pyridoxine add-on treatment for the control of behavioral adverse effects induced by levetiracetam in children: A case-control prospective study. The Annals of Pharmacotherapy, 52(7), 645–649. 
  36. Mascher, H. (1993). Determination of total pyridoxal in human plasma following oral administration of vitamin B6 by high-performance liquid chromatography with post-column derivatization. Journal of Pharmaceutical Sciences, 82(9), 972–974. 
  37. Masoumi, S. Z., Ataollahi, M., & Oshvandi, K. (2016). Effect of combined use of calcium and vitamin b6 on premenstrual syndrome symptoms: A randomized clinical trial. Journal of Caring Sciences, 5(1), 67–73. 
  38. Merrill, A. H., Jr, & Henderson, J. M. (1990). Vitamin B6 metabolism by human liver. Annals of the New York Academy of Sciences, 585, 110–117. 
  39. Miner, S. E., Cole, D. E., Evrovski, J., Forrest, Q., Hutchison, S., Holmes, K., & Ross, H. J. (2001). Pyridoxine improves endothelial function in cardiac transplant recipients. The Journal of Heart and Lung Transplantation, 20(9), 964–969. 
  40. Miodownik, C., Cohen, H., Kotler, M., & Lerner, V. (2003). [Vitamin B6 add-on therapy in treatment of schizophrenic patients with psychotic symptoms and movement disorders]. Harefuah, 142(8-9), 592–596, 647. 
  41. Miodownik, C., Lerner, V., Statsenko, N., Dwolatzky, T., Nemets, B., Berzak, E., & Bergman, J. (2006). Vitamin B6 versus mianserin and placebo in acute neuroleptic-induced akathisia: A randomized, double-blind, controlled study. Clinical Neuropharmacology, 29(2), 68–72. 
  42. Okada, H., Moriwaki, K., Kanno, Y., Sugahara, S., Nakamoto, H., Yoshizawa, M., & Suzuki, H. (2000). Vitamin B6 supplementation can improve peripheral polyneuropathy in patients with chronic renal failure on high-flux haemodialysis and human recombinant erythropoietin. Nephrology, Dialysis, Transplantation, 15(9), 1410–1413. 
  43. Parra, M., Stahl, S., & Hellmann, H. (2018). Vitamin b₆ and its role in cell metabolism and physiology. Cells, 7(7). 
  44. Romoli, M., Perucca, E., & Sen, A. (2020). Pyridoxine supplementation for levetiracetam-related neuropsychiatric adverse events: A systematic review. Epilepsy & Behavior, 103(Pt A), 106861. 
  45. Sadeghi, O., Nasiri, M., Maghsoudi, Z., Pahlavani, N., Rezaie, M., & Askari, G. (2015). Effects of pyridoxine supplementation on severity, frequency and duration of migraine attacks in migraine patients with aura: A double-blind randomized clinical trial study in Iran. Iranian Journal of Neurology, 14(2), 74–80. 
  46. Sahakian, V., Rouse, D., Sipes, S., Rose, N., & Niebyl, J. (1991). Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: A randomized, double-blind placebo-controlled study. Obstetrics and Gynecology, 78(1), 33–36. 
  47. Salam, R. A., Zuberi, N. F., & Bhutta, Z. A. (2015). Pyridoxine (vitamin B6) supplementation during pregnancy or labour for maternal and neonatal outcomes. Cochrane Database of Systematic Reviews, 6, CD000179. 
  48. Sato Y., Yasumiishi C., Chiba T., & Umegaki K. (2017). [A systematic review to identify unacceptable intake levels of vitamin b6 among patients taking levodopa]. Journal of the Food Hygienic Society of Japan, 58(6), 268–274. 
  49. Sermet, A., Aybak, M., Ulak, G., Güzel, C., & Denli, O. (1995). Effect of oral pyridoxine hydrochloride supplementation on in vitro platelet sensitivity to different agonists. Arzneimittel-Forschung, 45(1), 19–21. 
  50. Shams-Alizadeh, N., Bakhshayesh, H., Rezaei, F., Ghaderi, E., Shams-Alizadeh, N., & Hassanzadeh, K. (2018). Effect of vitamin B6 versus propranolol on antipsychotic-induced akathisia: A pilot comparative double-blind study. Iranian Journal of Pharmaceutical Research, 17(Suppl), 130–135. 
  51. Sharifzadeh, F., Kashanian, M., Koohpayehzadeh, J., Rezaian, F., Sheikhansari, N., & Eshraghi, N. (2018). A comparison between the effects of ginger, pyridoxine (vitamin B6) and placebo for the treatment of the first trimester nausea and vomiting of pregnancy (NVP). The Journal of Maternal-Fetal & Neonatal Medicine, 31(19), 2509–2514. 
  52. Shobeiri, F., Oshvandi, K., & Nazari, M. (2015). Clinical effectiveness of vitamin E and vitamin B6 for improving pain severity in cyclic mastalgia. Iranian Journal of Nursing and Midwifery Research, 20(6), 723–727. 
  53. Smith, C., Crowther, C., Willson, K., Hotham, N., & McMillian, V. (2004). A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstetrics and Gynecology, 103(4), 639–645. 
  54. Sripramote, M., & Lekhyananda, N. (2003). A randomized comparison of ginger and vitamin B6 in the treatment of nausea and vomiting of pregnancy. Journal of the Medical Association of Thailand, 86(9), 846–853. 
  55. Stover, P. J., & Field, M. S. (2015). Vitamin B-6. Advances in Nutrition, 6(1), 132–133. 
  56. Tardif, J.-C., Carrier, M., Kandzari, D. E., Emery, R., Cote, R., Heinonen, T., Zettler, M., Hasselblad, V., Guertin, M.-C., Harrington, R. A., & MEND-CABG Investigators. (2007). Effects of pyridoxal-5’-phosphate (MC-1) in patients undergoing high-risk coronary artery bypass surgery: Results of the MEND-CABG randomized study. The Journal of Thoracic and Cardiovascular Surgery, 133(6), 1604–1611. 
  57. Telen, M. J. (2020). Pyridoxamine: Another vitamin for sickle cell disease? Haematologica, 105(10), 2348–2350. 
  58. Var, C., Keller, S., Tung, R., Freeland, D., & Bazzano, A. N. (2014). Supplementation with vitamin B6 reduces side effects in Cambodian women using oral contraception. Nutrients, 6(9), 3353–3362. 
  59. Vrolijk, M. F., Opperhuizen, A., Jansen, E. H. J. M., Hageman, G. J., Bast, A., & Haenen, G. R. M. M. (2017). The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function. Toxicology in Vitro, 44, 206–212. 
  60. Wilson, M. P., Plecko, B., Mills, P. B., & Clayton, P. T. (2019). Disorders affecting vitamin B6 metabolism. Journal of Inherited Metabol ic Disease, 42(4), 629–646. 
  61. Wozenski, J. R., Leklem, J. E., & Miller, L. T. (1980). The metabolism of small doses of vitamin B-6 in men. The Journal of Nutrition, 110(2), 275–285. 
  62. Wyatt, K. M., Dimmock, P. W., Jones, P. W., & Shaughn O’Brien, P. M. (1999). Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: Systematic review. BMJ, 318(7195), 1375–1381. 
  63. Zempleni, J. (1995). Pharmacokinetics of vitamin B6 supplements in humans. Journal of the American College of Nutrition, 14(6), 579–586. 

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