Vitamin B6

• How It Works

  Obtaining vitamin B6 through diet may help to reduce the risk of certain cancers, but using B6 supplements does not prevent cancer or reduce chemotherapy side effects.

  Vitamin B6 is necessary for many physiological processes in the human body. These include reactions of cellular respiration, the release of glucose stores, and amino acid metabolism. Getting B6 through diet along with other nutrients is associated with cancer-preventive effects, but it cannot reduce side effects from chemotherapy. Even though lab studies show that B6 can have protective effects, high levels can also be toxic and cause nerve damage. B6 is readily available in food and deficiencies are uncommon. If a deficiency is suspected, it is important to see a healthcare practitioner to ensure correct diagnosis and supplement dosage.

• Purported Uses
  • To prevent cancer
    Various studies show that nutrients including B6 obtained through diet have cancer-preventive effects, but this does not mean these same effects occur with supplements. In fact, long-term use of vitamin B6 supplement may increase the risk of lung cancer in male smokers.
  • To treat chemotherapy skin reactions
    Several studies show that vitamin B6 therapy is ineffective in preventing hand and foot syndrome (HFS), a condition caused by certain chemotherapies, although one study suggests it may reduce the occurrence of severe HFS.
  • To treat peripheral neuropathy
    A randomized trial did not find that high-dose B6 was more effective than placebo.
  • To treat alcoholism
    Alcoholism can lead to deficiency in vitamin B6 and many other nutrients, so supplementation may help to improve nutritional status. However, proper diagnosis and treatment are needed.
  • To treat diabetes
    In a study using supplements including B6, the risk of developing type 2 diabetes was not reduced.
  • To manage heart disease and its risk factors
    High intakes of B6 obtained from foods are associated with lower levels of homocysteine, a risk factor for heart disease. B6 intake from food is also associated with reduced risk of death from stroke, heart disease, and heart failure. B6 may reduce high blood pressure in animals, but few studies about this have been done in humans.
  • To stimulate the immune system
    There is no scientific evidence to support this claim.
  • To treat pregnancy-related nausea and vomiting (morning sickness)
    Limited data provide weak evidence that B6 may help to prevent pregnancy-related nausea.
• Patient Warnings
  • Unexplained symptoms of nerve pain, lack of muscle control, or poor physical coordination may be a sign of excess B6 intake.
• Do Not Take If
  • You are receiving altretamine chemotherapy: B6 supplements may diminish its therapeutic effect.
  • You take levodopa for Parkinson’s disease: B6 supplements may reduce its effects.
  • You take seizure medications (phenytoin, phenobarbital): High-dose B6 may decrease blood levels of seizure drugs.
• Side Effects
  • Severe nerve problems and failure of muscular coordination with chronic intake of high doses
• Special Point
  • If a B6 deficiency is suspected, it is important to have a healthcare professional identify the cause and prescribe a safe dose of B6 supplementation if necessary.
  • Some drugs may increase the need for B6. These include isoniazide, penicillamine and oral contraceptives. Your healthcare professional should determine if this is the case and supplementation is needed.
• Scientific Name

  Pyridoxine

• Clinical Summary

  Vitamin B6 or pyridoxine, as part of the water-soluble vitamin B-complex family, is actually a mixture of 6 inter-convertible pyridine vitamers, or related compounds: pyridoxine, pyridoxamine, pyridoxal, and their 5′-phosphorylated forms ⁽¹⁾. Although plants and microorganisms can synthesize B6 on their own, humans must acquire it from dietary sources. Because vitamin B6 is abundant in meats, fish, poultry, shellfish, leafy green vegetables, legumes, fruits, and whole grains, deficiencies are rare. For example, patients taking the antituberculosis drug isoniazide need to take vitamin B6 to prevent drug-induced peripheral neuropathy. Patients may use supplemental B6 to treat symptoms related to heart disease, hypertension, morning sickness, peripheral neuropathies, carpal tunnel syndrome, and diabetes.

  Preclinical studies show that systemic administration of certain B vitamins including B6 has neuroprotective, antihypertensive ⁽²⁾, antinociceptive ⁽³⁾, and antitumor effects ⁽⁴⁾. In humans, higher B6 intake may lower serum homocysteine concentrations ⁽⁵⁾, but did not reduce the risk of developing type 2 diabetes ⁽⁶⁾. High dietary intakes of folate and B6 have been associated with reduced risk of mortality from stroke, coronary heart disease, and heart failure ⁽⁷⁾. Vitamin B6 supplementation did not improve cognition in older adults ⁽⁸⁾ and was not more effective than placebo for carpal tunnel syndrome ⁽⁹⁾. There is also limited evidence of its effect on asthma susceptibility or established disease ⁽¹⁰⁾. Data on its use for premenstrual syndrome is mixed ⁽¹¹⁾, and evidence is limited and weak for the prevention of pregnancy-related nausea ^(12) (13).

  Some studies suggest a beneficial role for vitamin B6 in preventing colorectal cancer ^{(14) (15) (16)}, and lower intake of dietary vitamin B6 is associated with increased risk of gastric adenocarcinoma ⁽¹⁷⁾ and pancreatic cancer ⁽¹⁸⁾. However, conclusions from the Women’s Health Study indicate that supplementation with vitamins B6, B12, and folate did not decrease breast cancer risk ⁽¹⁹⁾, nor did it have an effect on overall risk of invasive cancer or breast cancer ^(20) (21). Long-term vitamin B6 supplement intake is associated with increased risk of lung cancer, especially in male smokers ⁽⁴⁶⁾. Vitamin B6 administration is ineffective in preventing chemotherapy-associated hand-foot syndrome (HFS; also known as palmar-plantar erythrodysesthesia [PPE]) ^{(22) (23) (24) (25)}, with limited evidence suggesting that higher doses might be needed ⁽²⁶⁾. In one study, it did reduce the need for capecitabine dose modifications and incidence of severe HFS, but did not positively impact chemotherapy effects ⁽²⁷⁾. A multi-arm trial to evaluate therapies including high-dose B6 for peripheral neuropathy did not find it more effective than placebo ⁽²⁸⁾.

  High B6 intakes can have toxic effects including sensory and motor neuropathies, and some case reports of neurotoxicity have not been reversible ⁽²⁹⁾. B6 levels can also be elevated due to environmental exposures or genetic defects ⁽¹⁾.

• Food Sources

  Meats, fish, shellfish, poultry, leafy green vegetables, legumes, fruits, and whole grains ^{(5) (30) (31)}

• Purported Uses
  • Alcoholism
  • Cancer prevention
  • Cardiovascular disease
  • Chemotherapy skin reactions
  • Diabetes
  • Immunostimulation
  • Peripheral neuropathy
  • Pregnancy-related nausea and vomiting
• Mechanism of Action

  Vitamin B6 is a coenzyme in the folate metabolism pathway. Its phosphorylated metabolites are involved in amino acid metabolism, the transsulfuration pathway of homocysteine to cysteine, and glycogen phosphorylase activity which mobilizes glucose from glycogen ⁽³²⁾. It is a cofactor along with cystathionine b synthase and cystathionase to produce cysteine and glutathione from their precursor homocysteine ⁽³³⁾. Pyridoxal phosphate (PLP) is the major coenzyme form, the most abundant in animal tissue, and the cofactor for over 100 enzymes used in amino acid metabolism, including aminotransferases, decarboxylases, racemases, and dehydrases. It also facilitates mobilization of glucose units from glycogen via glycogen phosphorylase ⁽³²⁾. PLP is also the active antiemetic form of B6, of which pyridoxine and pyridoxal have been identified as prodrugs ⁽⁴⁵⁾.

  In animal models, an excess-pyridoxine diet actively influenced cell-mediated immunity via enhanced IFN-γ production and Th1-polarization ⁽³⁴⁾. In several cancer cell lines, B6 contributed to increased p21 gene expression via p53 activation ⁽⁴⁾. Proposed mechanisms for an inverse relationship of B6 intake and serum PLP with cancer risk include: 1) its participation in one-carbon metabolism that is essential for DNA synthesis, repair, and methylation; 2) the high uracil and chromosome breaks caused by B6 deficiency which may interfere with these processes leading to aberrant gene expression, DNA instability, and eventual disease; and 3) possible cancer-suppression effects through reductions in cell proliferation, angiogenesis, oxidative stress, inflammation, and nitric oxide synthesis ^(16) (21).

  At the same time, because PLP is the metabolically active form of B6, it is thought to be responsible for instances of vitamin B6 toxicity ⁽²⁹⁾. High circulating pyridoxine levels may have direct toxic effects on peripheral sensory ganglia neurons in the lower blood–nerve barrier, whereas the blood–brain barrier protects neurons in those regions from higher levels ⁽³⁵⁾. The negative impact of B6 upon levels of other B vitamins appears to be dose-dependent and occur with chronic exposure ⁽²⁹⁾.

• Warnings

  Long-term intake of high doses vitamin B6 can lead to nerve problems ⁽²⁹⁾.

• Adverse Reactions

  High concentrations of vitamin B6 may result in severe peripheral sensory neuropathies and ataxia. Toxicities have reversed following discontinuation in some instances ⁽³⁷⁾, but some case reports of neurotoxicity have not been reversible ⁽²⁹⁾.

  Case reports
  Irreversible sensory ataxia in octogenarians: Three elderly patients in their eighties presented with sensory ataxia (lack of voluntary coordination of muscle movements) and signs of polyneuropathy (damage or disease affecting peripheral nerves) for 3–8 months. Pyridoxine 600 mg daily was consumed for 3–10 years in a B1-6-12-combination tablet. B6 blood levels were markedly elevated at 66–104x ULN. After 2 years of vitamin discontinuation, the patients showed no significant improvement in either neuropathy or gait, and no other likely cause for neuropathy in these patients could be identified ⁽²⁹⁾.

  Severe sensorimotor neuropathy: Due to B6 hypervitaminosis in a 75-year-old white man, accompanied by yellowish-brown skin pigmentation. Discontinuation of B6 led to improvement 1 year later, when he no longer used a wheelchair and could walk without a cane. Skin color also resolved, but ataxic signs were still present ⁽³⁸⁾.

• Herb-Drug Interactions

  Altretamine: Pyridoxine may diminish its therapeutic effect ⁽³⁹⁾.
  Oral contraceptives: May moderately increase pyridoxine requirements ⁽⁴⁰⁾.
  Levodopa: Enhances levodopa metabolism, thereby reducing its effects ^(41) (42).
  Penicillamine: May increase the requirements for pyridoxine ⁽³²⁾.
  Seizure medications (phenytoin, phenobarbital): High-dose pyridoxine may decrease serum concentrations ⁽⁴³⁾.

• References

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  2. Vasdev S, Ford CA, Parai S, et al. Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats. Mol Cell Biochem. Oct 1999;200(1-2):155-162. doi:

  3. Yu CZ, Liu YP, Liu S, et al. Systematic administration of B vitamins attenuates neuropathic hyperalgesia and reduces spinal neuron injury following temporary spinal cord ischaemia in rats. Eur J Pain. Jan 2014;18(1):76-85. doi: 10.1002/j.1532-2149.2013.00390.x

  4. Zhang P, Suidasari S, Hasegawa T, et al. Vitamin B(6) activates p53 and elevates p21 gene expression in cancer cells and the mouse colon. Oncol Rep. May 2014;31(5):2371-2376. doi: 10.3892/or.2014.3073

  5. Murakami K, Sasaki S, Uenishi K, et al. Higher intake of vitamin B-6 and dairy products and lower intake of green and oolong tea are independently associated with lower serum homocysteine concentration in young Japanese women. Nutr Res. Aug 2013;33(8):653-660. doi: 10.1016/j.nutres.2013.05.010

  6. Song Y, Cook NR, Albert CM, et al. Effect of homocysteine-lowering treatment with folic Acid and B vitamins on risk of type 2 diabetes in women: a randomized, controlled trial. Diabetes. Aug 2009;58(8):1921-1928. doi: 10.2337/db09-0087

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  10. Sharma S, Litonjua A. Asthma, allergy, and responses to methyl donor supplements and nutrients. J Allergy Clin Immunol. May 2014;133(5):1246-1254. doi: 10.1016/j.jaci.2013.10.039

  11. Whelan AM, Jurgens TM, Naylor H. Herbs, vitamins and minerals in the treatment of premenstrual syndrome: a systematic review. Can J Clin Pharmacol. Fall 2009;16(3):e407-429. doi:

  12. Festin M. Nausea and vomiting in early pregnancy. Clin Evid (Online). 2014;2014. doi:

  13. Masino SA, Kahle JS. Vitamin B6 therapy during childbearing years: cause for caution? Nutr Neurosci. Sep 2002;5(4):241-242. doi: 10.1080/10284150290020745

  14. Larsson SC, Giovannucci E, Wolk A. Vitamin B6 intake, alcohol consumption, and colorectal cancer: a longitudinal population-based cohort of women. Gastroenterology. Jun 2005;128(7):1830-1837. doi:

  15. Theodoratou E, Farrington SM, Tenesa A, et al. Dietary vitamin B6 intake and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. Jan 2008;17(1):171-182. doi: 10.1158/1055-9965.EPI-07-0621

  16. Larsson SC, Orsini N, Wolk A. Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective studies. JAMA. Mar 17 2010;303(11):1077-1083. doi: 10.1001/jama.2010.263

  17. Eussen SJ, Vollset SE, Hustad S, et al. Vitamins B2 and B6 and genetic polymorphisms related to one-carbon metabolism as risk factors for gastric adenocarcinoma in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev. Jan 2010;19(1):28-38. doi: 10.1158/1055-9965.EPI-08-1096

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  19. Lin J, Lee IM, Cook NR, et al. Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women. Am J Clin Nutr. Mar 2008;87(3):734-743. doi:

  20. Zhang SM, Cook NR, Albert CM, et al. Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial. JAMA. Nov 5 2008;300(17):2012-2021. doi: 10.1001/jama.2008.555

  21. Wu W, Kang S, Zhang D. Association of vitamin B6, vitamin B12 and methionine with risk of breast cancer: a dose-response meta-analysis. Br J Cancer. Oct 1 2013;109(7):1926-1944. doi: 10.1038/bjc.2013.438

  22. Kang YK, Lee SS, Yoon DH, et al. Pyridoxine is not effective to prevent hand-foot syndrome associated with capecitabine therapy: results of a randomized, double-blind, placebo-controlled study. J Clin Oncol. Aug 20 2010;28(24):3824-3829. doi: 10.1200/JCO.2010.29.1807

  23. von Gruenigen V, Frasure H, Fusco N, et al. A double-blind, randomized trial of pyridoxine versus placebo for the prevention of pegylated liposomal doxorubicin-related hand-foot syndrome in gynecologic oncology patients. Cancer. Oct 15 2010;116(20):4735-4743. doi: 10.1002/cncr.25262

  24. Braik T, Yim B, Evans AT, et al. Randomized trial of vitamin B6 for preventing hand-foot syndrome from capecitabine chemotherapy. J Community Support Oncol. Feb 2014;12(2):65-70. doi:

  25. Zhou Y, Peng L, Li Y, et al. Prophylactic pyridoxine was not able to reduce the incidence of capecitabine-induced hand-foot syndrome: A meta-analysis. Biomed Rep. Nov 2013;1(6):873-878. doi: 10.3892/br.2013.161

  26. Chen M, Zhang L, Wang Q, et al. Pyridoxine for prevention of hand-foot syndrome caused by chemotherapy: a systematic review. PLoS One. 2013;8(8):e72245. doi: 10.1371/journal.pone.0072245

  27. Corrie PG, Bulusu R, Wilson CB, et al. A randomised study evaluating the use of pyridoxine to avoid capecitabine dose modifications. Br J Cancer. Aug 7 2012;107(4):585-587. doi: 10.1038/bjc.2012.318

  28. Rostock M, Jaroslawski K, Guethlin C, et al. Chemotherapy-induced peripheral neuropathy in cancer patients: a four-arm randomized trial on the effectiveness of electroacupuncture. Evid Based Complement Alternat Med. 2013;2013:349653. doi: 10.1155/2013/349653

  29. Kulkantrakorn K. Pyridoxine-induced sensory ataxic neuronopathy and neuropathy: revisited. Neurol Sci. Jul 24 2014. doi: 10.1007/s10072-014-1902-6

  30. Foods high in B vitamins may lower cardiovascular risks. Folate and vitamins B6 and B12 appear to be beneficial, but supplements should be taken only when recommended by a doctor. Heart Advis. Jul 2010;13(7):10-11.

  31. Sharma S, Sheehy T, Kolonel LN. Ethnic differences in grains consumption and their contribution to intake of B-vitamins: results of the Multiethnic Cohort Study. Nutr J. 2013;12:65. doi: 10.1186/1475-2891-12-65

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  33. Halsted CH, Medici V. Vitamin-dependent methionine metabolism and alcoholic liver disease. Adv Nutr. Sep 2011;2(5):421-427. doi: 10.3945/an.111.000661

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  35. Rao DB, Jortner BS, Sills RC. Animal models of peripheral neuropathy due to environmental toxicants. ILAR J. 2014;54(3):315-323. doi: 10.1093/ilar/ilt058

  36. Albersen M, Bosma M, Knoers NV, et al. The intestine plays a substantial role in human vitamin B6 metabolism: a Caco-2 cell model. PLoS One. 2013;8(1):e54113. doi: 10.1371/journal.pone.0054113

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  39. Wiernik PH, Yeap B, Vogl SE, et al. Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: a study of the Eastern Cooperative Oncology Group. Cancer Invest. 1992;10(1):1-9. doi:

  40. Veninga KS. Effects of oral contraceptives on vitamins B6, B12, C, and folacin. J Nurse Midwifery. Nov-Dec 1984;29(6):386-390. doi:

  41. Yahr MD, Duvoisin RC. Pyridoxine and levodopa in the treatment of Parkinsonism. JAMA. May 8 1972;220(6):861. doi:

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  43. Hansson O, Sillanpaa M. Letter: Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet. Jan 31 1976;1(7953):256. doi:

  44. Institute of Medicine. Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Available at: http://www.ncbi.nlm.nih.gov/books/NBK114310/. 1998 Accessed August 5, 2014.

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