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Vitamin B6 in Health Supplements and Neuropathy: Case Series Assessment of Spontaneously Reported Cases

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Abstract

Introduction

In the literature, vitamin B6 has been linked to the development of polyneuropathy. Most often, these complaints were seen when taking high doses of vitamin B6 for a long time. Evidence as to whether a lower dosage range of vitamin B6 (< 50 mg/day) can also induce neuropathy is scarce.

Objective

We aim to comprehensively describe the cases of neuropathy associated with vitamin B6 received by the Netherlands Pharmacovigilance Centre Lareb and to assess the case series concerning the use of vitamin B6 and neuropathic complaints.

Methods

We describe the number and nature of the reported cases, including suspect product, dosage, duration of use, and vitamin B6 serum levels. In addition, we describe the causality for the individual cases (Naranjo Probability Scale) and for the entire case series (Bradford Hill criteria).

Results

In total, 90 reports on products containing vitamin B6 included at least one adverse drug reaction in the standardized Medical Dictionary for Regulatory Activities (MedDRA®) query (SMQ; broad) ‘peripheral neuropathy’. The amount of vitamin B6 in the products varied between 1.4 and 100 mg per tablet. The serum vitamin B6 level was known in 36 cases (88–4338 nmol/l), and the mean serum vitamin B6 level was 907 nmol/l. However, no statistical correlation between dosage and vitamin B6 blood levels was found.

Discussion and Conclusion

Causality assessment of the case series of 90 reports to Lareb shows it is plausible for the vitamin B6 supplements to have caused complaints such as neuropathies. This is especially the case with higher dosages and prolonged use, but dosages < 50 mg/day also cannot be excluded.

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References

  1. Vrolijk MF, Opperhuizen A, Jansen EHJM, Hageman GJ, Bast A, Haenen GRMM. The vitamin B6 paradox: supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function. Toxicol In Vitro. 2017;44:206–12.

    Article  PubMed  CAS  Google Scholar 

  2. van Rossum CTM, Fransen HP, Verkaik-Kloosterman J, Buurma-Rethans EJM, Ocke MC. Dutch National Food Consumption Survey 2007-2010: Diet of children and adults aged 7 to 69 years. RIVM Rapport 350050006, 1-144. 7-7-2012. RIVM. Ref Type: Report.

  3. van der Watt JJ, Benatar MG, Harrison TB, Carrara H, Heckmann JM. Isoniazid exposure and pyridoxine levels in human immunodeficiency virus associated distal sensory neuropathy. Int J Tuberc Lung Dis. 2015;19(11):1312–9.

    Article  PubMed  Google Scholar 

  4. Porter K, Hoey L, Hughes CF, Ward M, McNulty H. Causes, consequences and public health implications of low B-vitamin status in ageing. Nutrients. 2016;8(11):725.

    Article  PubMed Central  CAS  Google Scholar 

  5. di Salvo ML, Safo MK, Contestabile R. Biomedical aspects of pyridoxal 5′-phosphate availability. Front Biosci (Elite Ed). 2012;4:897–913.

    Google Scholar 

  6. Steen G, Vlasveld LTH, Poot CC, Slot-Verhouven A, Castel AJ. Onderzoek naar referentiewaarden van laboratoriumonderzoek in een algemeen ziekenhuis: resultaten en bevindingen. Ned Tijdschr Klin Chem Labgeneesk. 2009;34(1):35–43.

    Google Scholar 

  7. Health Council of the Netherland. Dietary Reference Intakes: vitamin B6, folic acid, and vitamin B12. 2003/04. 2003. The Hague. Ref Type: Report.

  8. Scientific Committee on Food, Scientific Panel on Dietetic Products NaA. Tolerable uptake levels for vitamins and minerals. http://www.efsaeuropaeu/sites/default/files/efsa_rep/blobserver_assets/ndatolerableuil.pdf. 2006 [cited 8 Sept 2017].

  9. de Kruijk JR, Notermans NC. Sensory disturbances caused by multivitamin preparations. Ned Tijdschr Geneeskd. 2005;149(46):2541–4.

    PubMed  Google Scholar 

  10. Scott K, Zeris S, Kothari MJ. Elevated B6 levels and peripheral neuropathies. Electromyogr Clin Neurophysiol. 2008;48(5):219–23.

    PubMed  CAS  Google Scholar 

  11. Kulkantrakorn K. Pyridoxine-induced sensory ataxic neuronopathy and neuropathy: revisited. Neurol Sci. 2014;35(11):1827–30.

    Article  PubMed  Google Scholar 

  12. Dalton K, Dalton MJ. Characteristics of pyridoxine overdose neuropathy syndrome. Acta Neurol Scand. 1987;76(1):8–11.

    Article  PubMed  CAS  Google Scholar 

  13. Ghavanini AA, Kimpinski K. Revisiting the evidence for neuropathy caused by pyridoxine deficiency and excess. J Clin Neuromuscul Dis. 2014;16(1):25–31.

    Article  PubMed  Google Scholar 

  14. van Hunsel F, Venhuis BJ, Keizers PH, Kant A. A ‘natural’ weight loss product containing sibutramine. Drug Test Anal 2016;8(3–4):311–4.

    Article  PubMed  CAS  Google Scholar 

  15. Bijwerkingencentrum Lareb. Vitamine B6 in (multi)vitamine preparaten en neuropathie. https://www.lareb.nl/media/2991/pyridoxine-in-multivitaminepreparaten-en-neuropathie-_overzicht.pdf [cited 22 Feb 2018].

  16. Bijwerkingencentrum Lareb. Vitamine B6 in (multi)vitamine preparaten en neuropathie - update. https://www.larebnl/media/2927/signals_2016_pyridoxine_neuropathie_update.pdf. 2017. [cited 22 Feb 2018].

  17. Brown EG, Wood L, Wood S. The medical dictionary for regulatory activities (MedDRA). Drug Saf. 1999;20(2):109–17.

    Article  PubMed  CAS  Google Scholar 

  18. Bankowski Z, Bruppacher R, Crusius I. Reporting adverse drug reactions, definition of terms and criteria for their use. Council International Organizations of Medical Sciences (CIOMS). 32. 1999. Ref Type: Report.

  19. CIOMS Working Group IV. Benefit-risk balance for marketed drugs: Evaluating safety signals. 1998. Geneva. Ref Type: Report

  20. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239–45.

    Article  PubMed  CAS  Google Scholar 

  21. Hill AB. The environment and disease: association or causation? Proc R Soc Med. 1965;58:295–300.

    PubMed  PubMed Central  CAS  Google Scholar 

  22. Fedak KM, Bernal A, Capshaw ZA, Gross S. Applying the Bradford Hill criteria in the 21st century: how data integration has changed causal inference in molecular epidemiology. Emerg Themes Epidemiol. 2015;12:14.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Noren GN, Hopstadius J, Bate A. Shrinkage observed-to-expected ratios for robust and transparent large-scale pattern discovery. Stat Methods Med Res. 2013;22(1):57–69.

    Article  PubMed  Google Scholar 

  24. Bate A, Lindquist M, Edwards IR, Olsson S, Orre R, Lansner A, et al. A Bayesian neural network method for adverse drug reaction signal generation. Eur J Clin Pharmacol. 1998;54(4):315–21.

    Article  PubMed  CAS  Google Scholar 

  25. Mitwalli A, Blair G, Oreopoulos DG. Safety of intermediate doses of pyridoxine. Can Med Assoc J. 1984;131(1):14.

    PubMed  PubMed Central  CAS  Google Scholar 

  26. Brush MG, Bennett T, Hansen K. Pyridoxine in the treatment of premenstrual syndrome: a retrospective survey in 630 patients. Br J Clin Pract. 1988;42(11):448–52.

    PubMed  CAS  Google Scholar 

  27. Williams MJ, Harris RI, Dean BC. Controlled trial of pyridoxine in the premenstrual syndrome. J Int Med Res. 1985;13(3):174–9.

    Article  PubMed  CAS  Google Scholar 

  28. European Commissionhealth & Consumer Protection Directorate-GeneraL. Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Vitamin B. SCF/CS/NUT/UPPLEV/16 Final. 19-10-2000. 19-10-2000. Ref Type: Report.

  29. Gdynia HJ, Muller T, Sperfeld AD, Kuhnlein P, Otto M, Kassubek J, et al. Severe sensorimotor neuropathy after intake of highest dosages of vitamin B6. Neuromuscul Disord. 2008;18(2):156–8.

    Article  PubMed  Google Scholar 

  30. Morra M, Philipszoon HD, D’Andrea G, Cananzi AR, L’Erario R, Milone FF. Sensory and motor neuropathy caused by excessive ingestion of vitamin B6: a case report. Funct Neurol. 1993;8(6):429–32.

    PubMed  CAS  Google Scholar 

  31. Foca FJ. Motor and sensory neuropathy secondary to excessive pyridoxine ingestion. Arch Phys Med Rehabil. 1985;66(9):634–6.

    PubMed  CAS  Google Scholar 

  32. Peltier AC, Russell JW. Advances in understanding drug-induced neuropathies. Drug Saf. 2006;29(1):23–30.

    Article  PubMed  CAS  Google Scholar 

  33. Visser NA, Notermans NC, Degen LA, de Kruijk JR, van den Berg LH, Vrancken AF. Chronic idiopathic axonal polyneuropathy and vitamin B6: a controlled population-based study. J Peripher Nerv Syst. 2014;19(2):136–44.

    Article  PubMed  CAS  Google Scholar 

  34. Edwards IR. Causality assessment in pharmacovigilance: still a challenge. Drug Saf. 2017;40(5):365–72.

    Article  Google Scholar 

  35. Theophile H, Andre M, Miremont-Salame G, Arimone Y, Begaud B. Comparison of three methods (an updated logistic probabilistic method, the Naranjo and Liverpool algorithms) for the evaluation of routine pharmacovigilance case reports using consensual expert judgement as reference. Drug Saf 2013;36(10):1033–44.

    Article  PubMed  Google Scholar 

  36. Kane-Gill SL, Kirisci L, Pathak DS. Are the Naranjo criteria reliable and valid for determination of adverse drug reactions in the intensive care unit? Ann Pharmacother 2005;39(11):1823–7.

    Article  PubMed  Google Scholar 

  37. Teschke R, Schmidt-Taenzer W, Wolff A. Spontaneous reports of assumed herbal hepatotoxicity by black cohosh: is the liver-unspecific Naranjo scale precise enough to ascertain causality? Pharmacoepidemiol Drug Saf 2011;20(6):567–82.

    Article  PubMed  Google Scholar 

  38. Rolfes L, Kolfschoten J, van Hunsel F, van Puijenbroek E. The validity and reliability of a signal impact assessment tool. Pharmacoepidemiol Drug Saf. 2016;25(7):815–9.

    Article  PubMed  Google Scholar 

  39. Russom M, Tesfai D, Gebregiorgis S, Usman A, Mihreteab S, Bahta I, et al. Artesunate/amodiaquine-induced acute extrapyramidal reactions in children and younger adults: case series assessment. Drug Saf. 2016;39(8):763–8.

    Article  PubMed  CAS  Google Scholar 

  40. EFSA Panel on Dietetic Products NaAN. Dietary reference values for vitamin B6. EFSA J 2016;14(6):4485.

    Google Scholar 

  41. Dodge T, Kaufman A. What makes consumers think dietary supplements are safe and effective? The role of disclaimers and FDA approval. Health Psychol. 2007;26(4):513–7.

    Article  PubMed  Google Scholar 

  42. Netherlands Food and Consumer Product Safety Authority (NVWA). Vitamine B6 uit voedingssupplementen BuRO NVWA. https://www.nvwa.nl/documenten/risicobeoordeling/voedselveiligheid/archief/2016m/risicobeoordeling-buro-nvwa-inzake-veilige-maximaleruimte-voor-inname-van-vitamine-b6-uit-supplementen-naast-voeding. 2016 [cited 4 July 2017]; Available from https://www.nvwa.nl/.

  43. Rijksoverheid. Schippers stelt maximum norm vitamine B6. https://www.rijksoverheidnl/actueel/nieuws/2016/12/16/schippers-stelt-maximum-norm-vitamine-b6. 2016 [cited 6 Oct 2017].

  44. Bernstein AL. Vitamin B6 in clinical neurology. Ann N Y Acad Sci. 1990;585:250–60.

    Article  PubMed  CAS  Google Scholar 

  45. van Hunsel F, Harmark L, Pal S, Olsson S, van Grootheest K. Experiences with adverse drug reaction reporting by patients: an 11-country survey. Drug Saf. 2012;35(1):45–60.

    Article  PubMed  Google Scholar 

  46. Schaumburg H, Kaplan J, Windebank A, Vick N, Rasmus S, Pleasure D, et al. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med. 1983;309(8):445–8.

    Article  PubMed  CAS  Google Scholar 

  47. Dalton K. Pyridoxine overdose in premenstrual syndrome. Lancet. 1985;1(8438):1168–9.

    Article  PubMed  CAS  Google Scholar 

  48. Parry GJ, Bredesen DE. Sensory neuropathy with low-dose pyridoxine. Neurology. 1985;35(10):1466–8.

    Article  PubMed  CAS  Google Scholar 

  49. de Zeghler F, Przyrembel H, Chalmers RA, Wolff ED, Huijmans JG. Successful treatment of infantile type I primary hyperoxaluria complicated by pyridoxine toxicity. Lancet. 1985;2(8451):392–3.

    Article  Google Scholar 

  50. Friedman MA, Resnick JS, Baer RL. Subepidermal vesicular dermatosis and sensory peripheral neuropathy caused by pyridoxine abuse. J Am Acad Dermatol. 1986;14(5 Pt 2):915–7.

    Article  PubMed  CAS  Google Scholar 

  51. Waterston JA, Gilligan BS. Pyridoxine neuropathy. Med J Aust. 1987;146(12):640–2.

    PubMed  CAS  Google Scholar 

  52. Albin RL, Albers JW, Greenberg HS, Townsend JB, Lynn RB, Burke JM Jr, et al. Acute sensory neuropathy-neuronopathy from pyridoxine overdose. Neurology. 1987;37(11):1729–32.

    Article  PubMed  CAS  Google Scholar 

  53. Santoro L, Ragno M, Nucciotti R, Barbieri F, Caruso G. Pyridoxine neuropathy. A four-year electrophysiological and clinical follow-up of a severe case. Acta Neurol (Napoli). 1991;13(1):13–8.

    PubMed  CAS  Google Scholar 

  54. Berger AR, Schaumburg HH, Schroeder C, Apfel S, Reynolds R. Dose response, coasting, and differential fiber vulnerability in human toxic neuropathy: a prospective study of pyridoxine neurotoxicity. Neurology. 1992;42(7):1367–70.

    Article  PubMed  CAS  Google Scholar 

  55. Wyatt KM, Dimmock PW, Jones PW, Shaughn O’Brien PM. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review. BMJ. 1999;318(7195):1375–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Bacharach R, Lowden M, Ahmed A. Pyridoxine toxicity small fiber neuropathy with dysautonomia: a case report. J Clin Neuromuscul Dis. 2017;19(1):43–6.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Netherlands Pharmacovigilance Centre Lareb, 5237 MH, ’s-Hertogenbosch, The Netherlands

    Florence van Hunsel, Sonja van de Koppel, Eugène van Puijenbroek & Agnes Kant

  2. Department of Pharmacy: Pharmacotherapy and Pharmaceutical Care, University of Groningen, Groningen, The Netherlands

    Eugène van Puijenbroek

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  1. Florence van Hunsel
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  2. Sonja van de Koppel
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  3. Eugène van Puijenbroek
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Correspondence to Florence van Hunsel.

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Conflict of interest

Florence van Hunsel, Sonja van de Koppel, Eugène van Puijenbroek and Agnes Kant have no conflicts of interest.

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No sources of funding were used to assist in the preparation of this study.

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van Hunsel, F., van de Koppel, S., van Puijenbroek, E. et al. Vitamin B6 in Health Supplements and Neuropathy: Case Series Assessment of Spontaneously Reported Cases. Drug Saf 41, 859–869 (2018). https://doi.org/10.1007/s40264-018-0664-0

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