Health Care Professional Information

Scientific Name
Pyridoxine
Common Name

Pyridoxine hydrochloride, pyridoxal, pyridoxamine, pyridoxic acid, and the phosphorylated forms pyridoxal phosphate (PLP), pyridoxamine phosphate (PMP), and pyridoxine phosphate (PNP)

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, 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). 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
  • Carpal tunnel syndrome
  • Circulatory disorders
  • Cognition
  • Diabetes
  • Hand-foot syndrome
  • Hypertension
  • Immunostimulation
  • Peripheral neuropathy
  • Pregnancy-related nausea and vomiting
  • Premenstrual syndrome
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).

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 in 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).

Pharmacokinetics

B6 vitamers acquired from diet are recycled in a salvage pathway that involves ATP-dependent PLK and a flavin, mononucleotide-dependent pyridoxamine 5′- phosphate (PMP). Ingested phosphorylated B6 vitamers are first hydrolyzed by intestinal phosphatase to pyridoxal, pyridoxamine and pyridoxine. Pyridoxine glucosides are hydrolyzed by a glucosidase prior to absorption (1).

Absorption: Absorbed vitamers are rapidly cleared mostly by liver uptake, and phosphorylated by PLK. PNP and PMP are further oxidized to PLP by PNP-oxidase (1).

Distribution/Metabolism: PLP re-enters circulation bound to a lysine residue of albumin. However, the delivery of active cofactors to tissues requires hydrolysis of circulating PLP to pyridoxal via ecto-enzyme tissue nonspecific alkaline phosphatases. PLP-specific phosphatase is also present, especially in the brain where levels are higher. Intracellularly, pyridoxal is re-phosphorylated by PLK and targeted to newly synthesized apo-B6 enzymes (1).

A Caco-2 cell model also demonstrates that the intestines play a substantial role in human B6 metabolism, as demonstrated by uptake of PN, PM, and PL, and conversion of PN and PM into PL (36).

Excretion: All three unphosphorylated B6 vitamers are primarily excreted in the urine as 4-pyridoxic acid (4-PA) (36).

Warnings

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

Contraindications

Hypersensitivity to pyridoxine

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).

Literature Summary and Critique

Braik T, et al. Randomized trial of vitamin B6 for preventing hand-foot syndrome from capecitabine chemotherapy. J Community Support Oncol. 2014;12:65-70.
In this double-blind placebo-controlled study, pyridoxine was evaluated to see whether it could alleviate the dose-limiting toxicity of hand-foot syndrome (HFS) caused by taking the oral chemotherapy agent, capecitabine. A total of 77 eligible patients were randomly assigned to receive either daily pyridoxine 100 mg (n=38) or placebo (n=39) along with their prescribed capecitabine-chemotherapy regimen. Patients were observed for the first 4 cycles of treatment with the primary endpoint of HFS incidence and grade recorded. Capecitabine dosages were equally matched between both arms. HFS occurred after a median of 2 chemotherapy cycles in both groups: 10 of 38 (26%) patients in the pyridoxine group and 8 of 39 (21%) patients in the placebo group (P=.547), with HFS risk 5 percentage points higher in the pyridoxine group (95% CI for difference: −13 to +25 percentage points). Therefore investigators determined there was no true benefit from using pyridoxine, as no differences in HFS grades were observed.

Theodoratou E, et al. Dietary vitamin B6 intake and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2008;17:171-182.
A case-control study was conducted to determine if supplementation with vitamin B6 has a protective role against colorectal cancer. Subjects included 2,028 hospital-based cases and 2,722 population-based controls. Researchers reported an inverse and dose-dependent association between vitamin B6 intake and colorectal cancer. Well-designed randomized trials are needed to confirm this finding.

Lin J, et al. Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women. Am J Clin Nutr. 2008;87:734-743.
This prospective study evaluated any association between plasma concentrations of folate, B6, and B12, and risk of breast cancer. Researchers identified 848 cases of invasive breast cancer and 848 matched control subjects aged ≥45 years from the Women's Health Study. Results showed that plasma levels of folate, B6, and B12 were not associated with an overall risk of breast cancer. Therefore, supplementation with vitamins B6, B12, and folate may not reduce the risk of developing breast cancer. More studies are warranted.

Dosage (Inside MSKCC Only)
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References
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  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
  18. Jansen RJ, Robinson DP, Stolzenberg-Solomon RZ, et al. Nutrients from fruit and vegetable consumption reduce the risk of pancreatic cancer. J Gastrointest Cancer. Jun 2013;44(2):152-161. doi: 10.1007/s12029-012-9441-y
  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
  32. Clayton PT. B6-responsive disorders: a model of vitamin dependency. J Inherit Metab Dis. Apr-Jun 2006;29(2-3):317-326. doi: 10.1007/s10545-005-0243-2
  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
  34. Kobayashi C, Kurohane K, Imai Y. High dose dietary pyridoxine induces T-helper type 1 polarization and decreases contact hypersensitivity response to fluorescein isothiocyanate in mice. Biol Pharm Bull. 2012;35(4):532-538. doi:
  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
  37. Schaumburg H, Kaplan J, Windebank A, et al. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med. Aug 25 1983;309(8):445-448. doi: 10.1056/NEJM198308253090801
  38. Gdynia HJ, Muller T, Sperfeld AD, et al. Severe sensorimotor neuropathy after intake of highest dosages of vitamin B6. Neuromuscul Disord. Feb 2008;18(2):156-158. doi: 10.1016/j.nmd.2007.09.009
  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:
  42. Cotzias GC, Papavasiliou PS. Blocking the negative effects of pyridoxine on patients receiving levodopa. JAMA. Mar 1 1971;215(9):1504-1505. doi:
  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.

Consumer Information

How It Works

Bottom Line: 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.
  • To treat hand-foot syndrome
    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
    High intakes of B6 obtained from foods are associated with lower levels of homocysteine, which is 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.
  • To lower high blood pressure
    Lab studies suggest B6 may reduce high blood pressure in animals, but very few studies have been done in humans.
  • To improve cognition
    Using B6 supplements has not been shown to improve cognition in older adults.
  • To treat carpal tunnel syndrome
    Using B6 supplements has not been shown to be more effective than placebo for carpal tunnel syndrome.
  • To stimulate the immune system
    There is no scientific evidence to support this claim.
  • To treat pregnancy-related nausea and vomiting
    Limited data provide weak evidence that B6 may help to prevent pregnancy-related nausea.
  • To treat symptoms of premenstrual syndrome (PMS)
    Clinical studies show inconsistent results.
Research Evidence

Hand-foot syndrome
Chemotherapy drugs such as 5-fluorouracil and capecitabine can cause a side effect known as hand-foot syndrome, which causes impaired touch sensitivity, numbness, pain, and swelling in these areas. Several studies did not find vitamin B6 (pyridoxine) to be effective for this problem, although a review that looked at many studies suggests a higher dose may produce some effect. More studies would be needed to determine whether this is true and that these amounts are safe, given the potential toxicity associated with high-dose B6.

Cancer prevention
Several studies have looked at both B6 supplements and B6 obtained from diet to see what role either may play in cancer prevention. Evidence for the use of supplements is mixed, with some studies for colorectal cancer reporting benefit, but other studies for breast cancer and invasive cancers not showing benefit. Well-designed randomized trials are needed to confirm benefits that some studies have found with supplements. At the same time, dietary B6 obtained from eating a variety of healthy foods is shown to be cancer-preventive in large population studies, underscoring that it’s not just one nutrient but rather a combination of many nutrients as they exist in foods which offers these protective effects.

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.
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