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, is a water-soluble vitamin and a coenzyme in the folate metabolism pathway. Phosphorylated metabolites of pyridoxine are involved in amino acid metabolism, the transsulfuration pathway of homocysteine to cysteine, and glycogen phosphorylase, which mobilizes glucose from glycogen (2). Vitamin B6 is abundant in meats, fish, poultry, shellfish, leafy green vegetables, legumes, fruits, and whole grains. Patients use vitamin B6 for heart disease, hypertension, peripheral neuropathies, carpal tunnel syndrome, and diabetes.
Systemic administration of B6, 1 and 12 vitamins was shown to afford neuroprotection and antinociception during spinal cord injury due to temporary ischaemia in rats (25).
Preliminary data suggest that vitamin B6 may be of benefit for palmar-plantar erythrodysesthesia (PPE) (5) and carpal tunnel syndrome (7) (8), but additional studies are necessary. Studies of its efficacy in diabetes (6), heart disease (9) (10), premenstrual syndrome (11) (12) (13), and hypertension (14) show inconsistent results. Vitamin B6 supplementation was not effective in improving cognition in older adults (18).

Current data suggest a beneficial role of vitamin B6 in preventing colorectal cancer (15) (16) (21) and an inverse association was reported between vitamin B6 and risk of gastric adenocarcinoma (20). However, conclusions from the Women's Health Study indicate that supplementation with vitamins B6, B12, and folate did not decrease the risk of breast cancer (17) and a recent study reported that a combination of folate and vitamins B6 and B12 did not have an effect on overall risk of invasive cancer or breast cancer (19) (26) . Vitamin B6 administration is also ineffective in preventing chemotherapy associated hand and foot syndrome (22) (23), but a systematic review indicates that a higher concentration of pyridoxine may have some efficacy (27).

Infrequent adverse events include headache, nausea, sedation, and mild paresthesias (3). Chronic consumption of large doses may cause severe neuropathies (24), ataxia, respiratory difficulties, and profound sedation, although reversal usually occurs following discontinuation (4).

Food Sources

Meats, fish, poultry, shellfish, leafy green vegetables, legumes, fruits, and whole grains (1)

Purported Uses
  • Alcoholism
  • Asthma
  • Cardiovascular disease
  • Carpal tunnel syndrome
  • Circulatory disorders
  • Diabetes
  • Homocystinuria
  • Hypertension
  • Immunostimulation
  • Peripheral neuropathy
  • Pregnancy-related nausea and vomiting
  • Premenstrual syndrome
Mechanism of Action

Vitamin B6 is a water-soluble vitamin. It exists as an alcohol (pyridoxine, PN), aldehyde (pyridoxal, PL), or amine (pyridoxamine, PM). Pyridoxal-P (PLP), phosphorylated pyridoxal, is the major coenzyme form and the most abundant in animal tissue. PLP is the cofactor for over 100 enzymes used in amino acid metabolism, including aminotransferases, decarboxylases, racemases, and dehydrases. In particular, it acts as a coenzyme for cystathionine B-synthase and cystathionase in the transsulfuration pathway from homocysteine to cysteine. It also facilitates mobilization of glucose units from glycogen via glycogen phosphorylase.
(3)

Pharmacokinetics

Absorption:
Vitamin B6 is absorbed by nonsaturable passive diffusion. Absorption in the gut involves phosphatase-mediated hydrolysis followed by passive transport of the nonphosphorylated form into the mucosal cell (3).
Distribution/Metabolism:
Most of absorbed B6 is then phosphorylated to pyridoxal phosphate (PLP). PLP is the major form of the vitamin in plasma, where it is bound primarily to albumin. Nonphosphorylated B6 is distributed by erythrocytes. The bulk of B6 stores are in muscle (2) .
Excretion:
Elimination half-life is estimated to be 15-25 days. Metabolites of B6 are excreted primarily in the urine as 4-pyridoxic acid (4-PA). Other forms of the vitamin are also found in urine to a lesser extent. B6 is also excreted in the feces, but microbial synthesis of B6 in the lower gut makes it difficult to evaluate the extent of excretion (3).

Adverse Reactions
  • High concentrations of vitamin B6 may result in severe peripheral sensory neuropathies, ataxia, respiratory difficulties, profound sedation, and vomiting. Toxicities appear reversible following discontinuation.
    (24)
Literature Summary and Critique

Theodoratou E, Farrington SM, Tenesa A, et al. Dietary vitamin B6 intake and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2008;17(1):171-82.
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 report 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, 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. 2008;87(3):734-43.
This is a prospective study to evaluate any association between plasma concentrations of folate, vitamin 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 and vitamins B6 and B12 were not associated with 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
  1. Whitney EN, et al. Understanding Normal & Clinical Nutrition, 4th ed. Belmont (CA): West Publishing; 1994.
  2. Zempleni J. Pharmacokinetics of vitamin B6 supplements in humans. J Am Coll Nutr 1995;14:579-86
  3. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington (DC): National Academy Press; 2000.
  4. Pronsky ZM. Power's and Moore's Food-Medication Interactions, 11th ed. Pottstown (PA): Food Medication Interactions; 2000.
  5. Fabian CJ, et al. Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with continuous 5-fluorouracil infusion. Invest New Drugs 1990;8:57-63.
  6. Levin ER, et al. The influence of pyridoxine in diabetic neuropathy. Diabetes Care 1981;4:606-9.
  7. Bernstein AL,.Dinesen JS. Brief communication: effect of pharmacologic doses of vitamin B6 on carpal tunnel syndrome, electroencephalographic results, and pain. J Am Coll.Nutr. 1993;12:73-6.
  8. Smith GP, Rudge PJ, Peters TJ. Biochemical studies of pyridoxal and pyridoxal phosphate status and therapeutic trial of pyridoxine in patients with carpal tunnel syndrome. Ann.Neurol. 1984;15:104-7.
  9. Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 1998;279:359-64.
  10. Robinson K, Arheart K, Refsum H, Brattstrom L, Boers G, Ueland P et al. Low circulating folate and vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. European COMAC Group. Circulation 1998;97:437-43. PM:9490237
  11. Kleijnen J, ter Riet G, Knipschild P. Vitamin B6 in the treatment of the premenstrual syndrome—a review. Br J Obstet.Gynaecol. 1990;97:847-52. PM:2242373
  12. Kendall KE,.Schnurr PP. The effects of vitamin B6 supplementation on premenstrual symptoms. Obstet.Gynecol. PM:3299182 1987;70:145-9.
  13. De Souza MC, Walker AF, Robinson PA, Bolland K. 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;9:131-9. PM:10746516
  14. Aybak M, Sermet A, Ayyildiz MO, Karakilcik AZ. Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension. Arzneimittelforschung. 1995;45:1271-3. PM:8595083
  15. Larsson SC, Giovannucci E, Wolk, A. Vitamin B6 Intake, alcohol consumption, and colorectal cancerL A longitudinal population-based cohort of women. Gastroenterology. 2005;128:1830-1837.
  16. Theodoratou E, Farrington SM, Tenesa A, et al. Dietary vitamin B6 intake and the risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2008;17(1):171-82.
  17. 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. 2008;87(3):734-43.
  18. van Uffelen JG, Chinapaw MJ, van Mechelen W, et al. Walking or vitamin B for cognition in older adults with mild cognitive impairment? A randomized controlled trial. Br J Sports Med. 2008.
  19. 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. 2008 Nov 5;300(17):2012-21.
  20. 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. 2010 Jan;19(1):28-38.
  21. Larsson SC, Orsini N, Wolk A. Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective studies. JAMA. 2010 Mar 17;303(11):1077-83.
  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. 2010 Aug 20;28(24):3824-9.
  23. von Gruenigen V, Frasure H, Fusco N, DeBernardo R, Eldermire E, Eaton S, Waggoner S. 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. 2010 Oct 15;116(20):4735-43.
  24. Schaumburg H, Kaplan J, Windebank A, et al. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med. 1983 Aug 25;309(8):445-8.
  25. 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. 2013 Sep 5. [Epub ahead of print]
  26. 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. 2013 Aug 1. [Epub ahead of print]
  27. Chen M, Zhang L, Wang Q, Shen J. Pyridoxine for prevention of hand-foot syndrome caused by chemotherapy: a systematic review.PLoS One. 2013 Aug 20;8(8):e72245.

Consumer Information

How It Works

Bottom Line: Vitamin B6 is not beneficial in the treatment of asthma, circulatory disorders, or PMS. Whether it is effective for heart disease, carpal tunnel syndrome, diabetic neuropathy, or cancer is undetermined.

Vitamin B6 is necessary for over 100 physiological processes in the human body. These include reactions of cellular respiration, the release of glucose stores, and amino acid metabolism. In conditions in which this vitamin is depleted from the body, vitamin B6 supplements are thought to be helpful. Although scientists are very familiar with the normal role of vitamin B6 in the body, it is not known if extra B6 will have any benefits.

Purported Uses
  • To treat alcoholism
    Alcoholism can lead to deficiency in vitamin B6 and many other nutrients, so supplementation may help to improve nutritional status.
  • To treat asthma
    A clinical trial did not find usefulness of vitamin B6 in releiving symptoms of asthma.
  • To manage heart disease
    Clinical studies show inconsistent results.
  • To treat carpal tunnel syndrome
    Some preliminary clinical trials support this use, but further research is needed.
  • To manage circulatory disorders
    No scientific evidence supports this use.
  • To treat diabetes
    Clinical studies show inconsistent results.
  • To treat homocystinuria
    Pyridoxine (vitamin B6) is currently used as a mainstream treatment for homocystinuria.
  • To lower high blood pressure
    Clinical studies show inconsistent results.
  • To stimulate the immune system
    There is no scientific evidence to support this claim.
  • To treat pregnancy-related nausea and vomiting
    A few clinical trials support this use.
  • To treat the symptoms of premenstrual syndrome (PMS)
    Clinical studies show inconsistent results.
  • To treat palmar-plantar erythrodyesthesia
    Some preliminary clinical trials support this use, but further research is needed.
Research Evidence

Palmar-plantar erythrodysesthesia (PPE):
The chemotherapy drug 5-fluorouracil can often cause palmar-plantar erythrodysesthesia (PPE) as a side effect. The ability of 50 or 150 mg of vitamin B6 (pyridoxine) daily to treat PPE was tested in five patients who were beginning to develop its symptoms from 5-fluorouracil (5-FU). Four out of five patients experienced an improvement in their symptoms, and were able to continue 5-FU therapy for a longer time than patients not taking vitamin B6. These results are promising, but larger clinical trials would help support this use of vitamin B6.

Diabetic neuropathy:
Peripheral neuropathy is a common complication of diabetes. A small clinical trial assessed the use of vitamin B6 for the treatment of diabetic neuropathy. Eighteen diabetic patients enrolled; nine were given 50 mg of pyridoxine every eight hours, the other nine were given a placebo pill every eight hours. Six of the patients taking vitamin B6 and four taking placebo reported improvements in their symptoms, indicating that vitamin B6 did not have a huge effect. Nerve conduction tests were performed on all patients and showed that vitamin B6 did not improve nerve firing, either. However, because these groups are so small, it is difficult to see an effect from vitamin B6, and larger clinical trials are needed.

Side Effects
  • Chronic intake of high concentrations of vitamin B6 may result in severe peripheral sensory nerve problems, ataxia (failure of muscular coordination), respiratory difficulties, profound sedation, and vomiting. Toxicities appear to be reversible once vitamin B6 is discontinued.
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