Purpose 

Vitamin B6 is a crucial water-soluble vitamin found in many foods and is involved in numerous physiological processes, including neurotransmitter synthesis and nervous system function. Although essential for overall health, both deficiency and excessive intake of vitamin B6 may lead to health complications, particularly peripheral neuropathy. This consensus statement aims to provide healthcare professionals with clear guidance on the safe and effective use of vitamin B6, focusing on its benefits, risks, recommended dosages, and treatment course.

Methods

This consensus statement was developed using a Delphi approach involving a panel of six experts from various medical specialties. This process includes a comprehensive literature review, two rounds of anonymous online surveys, and a virtual expert roundtable discussion. The GRADE approach was used to assess the quality of evidence for each recommendation.

Results

The expert panel reached consensus on five key statements. These key recommendations encompass the function of vitamin B6, complications due to vitamin B6 deficiency, dosage recommendations, adverse events, and monitoring guidance throughout the course of treatment. A washout period of 20-40 days for the complete clearance of vitamin B6 was calculated based on pharmacokinetic parameters. A clinical pathway for managing patients who might benefit from vitamin B6 treatment was proposed.

Conclusion

This consensus statement highlights the importance of recognizing the benefits and potential risks of vitamin B6. While the therapeutic dosage of vitamin B6 can be beneficial to treat deficiency, excessive intake can lead to adverse effects. This statement emphasizes the need for individualized patient care considering factors such as medical history, lifestyle, and potential drug interactions. Further research is needed to establish clearer dosage guidelines, understand the mechanisms of vitamin B6-induced neurological side effects, and optimize patient outcomes.

Keywords

clinical guidance; consensus statement; neuropathy; pyridoxine; safety; vitamin B6.

1. Hossain, K. S., Amarasena, S., & Mayengbam, S. (2022). B vitamins and their roles in gut health. Microorganisms, 10(6), Article 1168. https://doi.org/10.3390/microorganisms10061168
2. Percudani, R., & Peracchi, A. (2009). The B6 database: A tool for the description and classification of vitamin B6-dependent enzymatic activities and of the corresponding protein families. BMC Bioinformatics, 10(1), Article 273. https://doi.org/10.1186/1471-2105-10-273
3. Calderón‐Ospina, C. A., & Nava‐Mesa, M. O. (2020). B vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin. CNS Neuroscience & Therapeutics, 26(1), 5–13. https://doi.org/10.1111/cns.13207
4. Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and Its Panel on Folate, Other B Vitamins, and Choline. (1998). Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. National Academies Press. https://doi.org/10.17226/6015
5. Abosamak, N., & Gupta, V. (2023). Vitamin B6 (Pyridoxine). In StatPearls. StatPearls Publishing.
6. Zempleni, J. (1995). Pharmacokinetics of vitamin B6 supplements in humans. Journal of the American College of Nutrition, 14(6), 579–586. https://doi.org/10.1080/07315724.1995.10718546
7. Van Den Eynde, M. D. G., Scheijen, J. L. J. M., Stehouwer, C. D. A., Miyata, T., & Schalkwijk, C. G. (2021). Quantification of the B6 vitamers in human plasma and urine in a study with pyridoxamine as an oral supplement; pyridoxamine as an alternative for pyridoxine. Clinical Nutrition, 40(7), 4624–4632. https://doi.org/10.1016/j.clnu.2021.05.028
8. Ueland, P. M., McCann, A., Midttun, Ø., & Ulvik, A. (2017). Inflammation, vitamin B6 and related pathways. Molecular Aspects of Medicine, 53, 10–27. https://doi.org/10.1016/j.mam.2016.08.001
9. Vrolijk, M. F., Hageman, G. J., Van De Koppel, S., Van Hunsel, F., & Bast, A. (2020). Inter-individual differences in pharmacokinetics of vitamin B6: A possible explanation of different sensitivity to its neuropathic effects. PharmaNutrition, 12, Article 100188. https://doi.org/10.1016/j.phanu.2020.100188
10. Schellack, G., Harirari, P., & Schellack, N. (2015). B-complex vitamin deficiency and supplementation. South African Pharmaceutical Journal, 82(4), 28–33.
11. Parra, M., Stahl, S., & Hellmann, H. (2018). Vitamin B6 and its role in cell metabolism and physiology. Cells, 7(7), Article 84. https://doi.org/10.3390/cells7070084
12. Snider, D. E. (1980). Pyridoxine supplementation during isoniazid therapy. Tubercle, 61(4), 191–196. https://doi.org/10.1016/0041-3879(80)90038-0
13. Silviana, M., Tugasworo, D., & Belladonna, M. (2021). Efficacy of vitamin B1, B6, and B12 forte therapy in peripheral neuropathy patients. Diponegoro International Medical Journal, 2(1), 14–19. https://doi.org/10.14710/dimj.v2i1.9549
14. Jeenia, F. T., Sojib, F. A., Rahman, M. S., Ara, T., Khan, R., & Tanin, M. J. (2021). Neuroprotective effect of vitamin B6 and vitamin B12 against vincristine-induced peripheral neuropathy: A randomized, double-blind, placebo controlled, multicenter trial. Journal of Pharmacy and Pharmacology Research. Advance online publication. https://doi.org/10.1101/2021.05.18.21257296
15. Hakim, M., Kurniani, N., Pinzon, R. T., et al. (2018). Management of peripheral neuropathy symptoms with a fixed dose combination of high-dose vitamin B1, B6 and B12: A 12-week prospective non-interventional study in Indonesia. Asian Journal of Medical Sciences, 9(1), 32–40. https://doi.org/10.3126/ajms.v9i1.18510
16. Muhamad, R., Akrivaki, A., Papagiannopoulou, G., Zavridis, P., & Zis, P. (2023). The role of vitamin B6 in peripheral neuropathy: A systematic review. Nutrients, 15(13), Article 2823. https://doi.org/10.3390/nu15132823
17. Van Hunsel, F., Van De Koppel, S., Van Puijenbroek, E., & Kant, A. (2018). Vitamin B6 in health supplements and neuropathy: Case series assessment of spontaneously reported cases. Drug Safety, 41(9), 859–869. https://doi.org/10.1007/s40264-018-0664-0
18. Hadtstein, F., & Vrolijk, M. (2021). Vitamin B-6-induced neuropathy: Exploring the mechanisms of pyridoxine toxicity. Advances in Nutrition, 12(5), 1911–1929. https://doi.org/10.1093/advances/nmab033
19. Malouf, R., & Grimley Evans, J. (2003). Vitamin B6 for cognition. Cochrane Database of Systematic Reviews, (4), Article CD004393. https://doi.org/10.1002/14651858.CD004393
20. Health Sciences Authority (HSA). (2023). High-dose vitamin B6 and risk of peripheral neuropathy. https://www.hsa.gov.sg/announcements/safety-alert/high-dose-vitamin-b6-and-risk-of-peripheral-neuropathy
21. Therapeutic Goods Administration (TGA). (2022). Health supplements containing vitamin B6 can cause peripheral neuropathy. https://www.tga.gov.au/news/safety-alerts/health-supplements-containing-vitamin-b6-can-cause-peripheral-neuropathy
22. 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. https://doi.org/10.1016/j.tiv.2017.07.009
23. Nasa, P., Jain, R., & Juneja, D. (2021). Delphi methodology in healthcare research: How to decide its appropriateness. World Journal of Methodology, 11(4), 116–129. https://doi.org/10.5662/wjm.v11.i4.116
24. Sathienluckana, T., Palapinyo, S., Yotsombut, K., Wanothayaroj, E., Sithinamsuwan, P., & Suksomboon, N. (2024). Expert consensus guidelines for community pharmacists in the management of diabetic peripheral neuropathy with a combination of neurotropic B vitamins. Journal of Pharmaceutical Policy and Practice, 17(1), Article 2306866. https://doi.org/10.1080/20523211.2024.2306866
25. Ziegler, D., Tesfaye, S., Spallone, V., et al. (2022). Screening, diagnosis and management of diabetic sensorimotor polyneuropathy in clinical practice: International expert consensus recommendations. Diabetes Research and Clinical Practice, 186, Article 109063. https://doi.org/10.1016/j.diabres.2021.109063
26. Guyatt, G. H., Oxman, A. D., Vist, G. E., et al. (2008). GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ, 336(7650), 924–926. https://doi.org/10.1136/bmj.39489.470347.AD
27. Birch, T. W., Gyorgy, P., & Harris, L. W. (1935). The vitamin B(2) complex. Differentiation of the antiblacktongue and the “P.-P.” factors from lactoflavin and vitamin B(6) (so-called “rat pellagra” factor). Parts I-VI. Biochemical Journal, 29(12), 2830–2850. https://doi.org/10.1042/bj0292830
28. Rioult-Pedotti, M. S., Pekanovic, A., Atiemo, C. O., Marshall, J., & Luft, A. R. (2015). Dopamine promotes motor cortex plasticity and motor skill learning via PLC activation. PLoS One, 10(5), Article e0124986. https://doi.org/10.1371/journal.pone.0124986
29. Gwak, Y. S., & Hulsebosch, C. E. (2011). GABA and central neuropathic pain following spinal cord injury. Neuropharmacology, 60(5), 799–808. https://doi.org/10.1016/j.neuropharm.2010.12.030
30. Young, N. S., & Leyton, M. (2002). The role of serotonin in human mood and social interaction: Insight from altered tryptophan levels. Pharmacology Biochemistry and Behavior, 71(4), 857–865. https://doi.org/10.1016/s0091-3057(01)00670-0
31. Roth-Maier, D. A., Kettler, S. I., & Kirchgessner, M. (2002). Availability of vitamin B 6 from different food sources. International Journal of Food Sciences and Nutrition, 53(2), 171–179. https://doi.org/10.1080/09637480220132184
32. Raskin, N. H., & Fishman, R. A. (1965). Pyridoxine-deficiency neuropathy due to hydralazine. New England Journal of Medicine, 273(22), 1182–1185. https://doi.org/10.1056/NEJM196511252732203
33. Nair, S., Maguire, W., & Baron, H. (1976). The effect of cycloserine on pyridoxine-dependent metabolism in tuberculosis. Journal of Clinical Pharmacology, 16(8–9), 439–443. https://doi.org/10.1002/j.1552-4604.1976.tb02419.x
34. Hoyumpa, A. M. (1986). Mechanisms of vitamin deficiencies in alcoholism. Alcoholism: Clinical and Experimental Research, 10(6), 573–581. https://doi.org/10.1111/j.1530-0277.1986.tb05147.x
35. World Health Organization & Food and Agriculture Organization of the United Nations. (2004). Vitamin and mineral requirements in human nutrition (2nd ed.). World Health Organization.
36. Ghavanini, A. A., & Kimpinski, K. (2014). Revisiting the evidence for neuropathy caused by pyridoxine deficiency and excess. Journal of Clinical Neuromuscular Disease, 16(1), 25–31. https://doi.org/10.1097/CND.0000000000000049
37. National Health and Medical Research Council. (2006). Nutrient reference values for Australia and New Zealand: Including recommended dietary intakes. National Health and Medical Research Council; Ministry of Health. https://www.nhmrc.gov.au/about-us/publications/nutrient-reference-values-australia-and-new-zealand-including-recommended-dietary-intakes
38. Bernstein, A. L. (1990). Vitamin B 6 in clinical neurology. Annals of the New York Academy of Sciences, 585(1), 250–260. https://doi.org/10.1111/j.1749-6632.1990.tb28058.x
39. Pietrzik, K., & Hages, M. (1991). Risk/benefit evaluation of a high dose B vitamin therapy. In Pharmacology and clinical applications of high-dose B-vitamins (pp. 115–124). Steinkopff.
40. Coughlin, C. R., Tseng, L. A., Abdenur, J. E., et al. (2021). Consensus guidelines for the diagnosis and management of pyridoxine‐dependent epilepsy due to α‐aminoadipic semialdehyde dehydrogenase deficiency. Journal of Inherited Metabolic Disease, 44(1), 178–192. https://doi.org/10.1002/jimd.12332
41. Janka, H. U., Rietzel, S., & Mehnert, H. (1991). The influence of neurobion on temperature sensibility in patients with diabetic polyneuropathy. In Pharmakologie und klinische anwendung hochdosierter B-vitamine (pp. 87–97). Steinkopff.
42. Lheureux, P., Penaloza, A., & Gris, M. (2005). Pyridoxine in clinical toxicology: A review. European Journal of Emergency Medicine, 12(2), 78–85. https://doi.org/10.1097/00063110-200504000-00007
43. Krishnan, D., & Kiernan, M. C. (2023). Neurotoxic risks from over‐the‐counter vitamin supplements. Medical Journal of Australia, 218(7), 304–306. https://doi.org/10.5694/mja2.51851
44. Echaniz-Laguna, A., Mourot-Cottet, R., Noel, E., & Chanson, J. B. (2018). Regressive pyridoxine-induced sensory neuronopathy in a patient with homocystinuria. BMJ Case Reports, 11(1), Article bcr-2018-225059. https://doi.org/10.1136/bcr-2018-225059
45. Kulkantrakorn, K. (2014). Pyridoxine-induced sensory ataxic neuronopathy and neuropathy: Revisited. Neurological Sciences, 35(11), 1827–1830. https://doi.org/10.1007/s10072-014-1902-6
46. Visser, N. A., Notermans, N. C., Degen, L. A. R., De Kruijk, J. R., Van Den Berg, L. H., & Vrancken, A. F. J. E. (2014). Chronic idiopathic axonal polyneuropathy and vitamin B6: A controlled population‐based study. Journal of the Peripheral Nervous System, 19(2), 136–144. https://doi.org/10.1111/jns5.12063
47. Dalton, K., & Dalton, M. J. T. (1987). Characteristics of pyridoxine overdose neuropathy syndrome. Acta Neurologica Scandinavica, 76(1), 8–11. https://doi.org/10.1111/j.1600-0404.1987.tb03536.x
48. Parry, G. J., & Bredesen, D. E. (1985). Sensory neuropathy with low‐dose pyridoxine. Neurology, 35(10), 1466–1467. https://doi.org/10.1212/WNL.35.10.1466
49. Mayo Clinic Laboratories. (2025). Vitamin B6 profile (pyridoxal 5-phosphate and pyridoxic acid), plasma. https://www.mayocliniclabs.com/test-catalog/overview/42360#
50. Howland, R. H. (2009). Medication holidays. Journal of Psychosocial Nursing and Mental Health Services, 47(9), 15–18. https://doi.org/10.3928/02793695-20090804-01
51. Romano, S., Ferraldeschi, M., Bagnato, F., et al. (2019). Drug holiday of interferon beta 1b in multiple sclerosis: A pilot, randomized, single blind study of non-inferiority. Frontiers in Neurology, 10, Article 695. https://doi.org/10.3389/fneur.2019.00695
52. Center for Drug Evaluation and Research (CDER). (2016). Cross discipline team leader review: Bonjesta (NDA 209661Orig1s000). U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/209661Orig1s000Approv.pdf
53. Center for Drug Evaluation and Research (CDER). (2021). Bioequivalence studies with pharmacokinetic endpoints for drugs submitted under an ANDA guidance for industry. U.S. Food and Drug Administration. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bioequivalence-studies-pharmacokinetic-endpoints-drugs-submitted-under-abbreviated-new-drug
54. Committee for Medicinal Products for Human Use (CHMP). (2010). Guideline on the investigation of bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1/ Corr *). European Medicines Agency. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-bioequivalence-rev1_en.pdf
55. Health Canada. (2018). Guidance document: Conduct and analysis of comparative bioavailability studies. Government of Canada. https://www.canada.ca/content/dam/hc-sc/documents/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/bioavailability-bioequivalence/conduct-analysis-comparative.pdf