Vitamin B6 (PLP) and Neural Tube Defects: Is There an Association?

  • Lydia A. Afman
  • Nathalie M. J. van der Put
  • Chris M. G. Thomas
  • Frans J. M. Trijbels
  • Henk J. Blom

Abstract

Neural tube defects (NTD) originate from an incomplete closure of the neural tube and are one of the most common and severe congenital malformations. The aetiology of NTD is multifactorial, indicating a combination of environmental and genetic factors. One of the most important environmental factors is the maternal vitamin status. Periconceptional folic acid supplementation can prevent about 60% of the NTD cases (1, 2). The exact preventive mechanism of folate on the occurrence and recurrence of NTD is unknown. Folate in the form of 5-methyltetrahydrofolate (5-meTHF) is required for the remethylation of homocysteine to methionine by the enzyme methionine synthase (MS). Therefore, a deficiency in folate may result in elevated plasma homocysteine concentrations. Although mothers of NTD children are not deficient in folate, their folate levels are in the lower range of the control levels and their plasma homocysteine concentrations are elevated (3, 4, 5). The 677C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is the first genetic risk factor for NTD and is partly responsible for these changes in homocysteine concentrations (6). Another vitamin involved in the methylation of homocysteine is vitamin B12, which functions as a cofactor of methionine synthase (MS). Some studies showed an association between decreased plasma vitamin B12 levels or decreased plasma holo-transcobalamin (holo-tc) levels and NTD (7, 8).

Keywords

HPLC Glycine Cysteine Serine Folate 

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References

  1. 1.
    Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet 338: 131–137, 1991.Google Scholar
  2. 2.
    Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by  periconceptional vitamin supplementation. N. Engl. J. Med. 327: 1832–1835Google Scholar
  3. 3.
    Steegers-Theunissen RP, Boers GH, Trijbels FJ, et al. Maternal hyperhomocysteinemia: a risk factor for neural-tube defects? Metabolism 43: 1475–1480, 1994.PubMedCrossRefGoogle Scholar
  4. 4.
    Mills JL, McPartlin JM, Kirke PN, et al. Homocysteine metabolism in pregnancies complicated by neural-tube defects. Lancet 345: 149–151, 1995.PubMedCrossRefGoogle Scholar
  5. 5.
    van der Put NM, Thomas CM, Eskes TK, et al. Altered folate and vitamin B12 metabolism in families with spina bifida offspring. Quart. J. Med. 90: 505–510, 1997.CrossRefGoogle Scholar
  6. 6.
    van der Put NM, Steegers-Theunissen RP, Frosst P, et al. Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet 346: 1070–1071, 1995.PubMedCrossRefGoogle Scholar
  7. 7.
    Kirke PN, Molloy AM, Daly LE, Burke H, Weir DG, Scott JM. Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects. Quart. J. Med. 86: 703–708, 1993.PubMedGoogle Scholar
  8. 8.
    Afman LA, van der Put NM, Thomas CM, Trijbels JM, Blom HJ. Reduced vitamin B12 binding by transcobalamin II increases the risk of neural tube defects. Quart. J. Med. 94:159–166, 2001.CrossRefGoogle Scholar
  9. 9.
    Stover PJ, Chen LH, Suh JR, Stover DM, Keyomarsi K, Shane B. Molecular cloning, characterization, and regulation of the human mitochondrial serine hydroxymethyltransferase gene. J. Biol. Chem. 272: 1842–1848, 1997.PubMedCrossRefGoogle Scholar
  10. 10.
    Pyridoxine and pyridoxal 5′ phosphate — Monograph. Altern. Med Rev. 6: 87–92, 2001.Google Scholar
  11. 11.
    Bender DA. Non-nutritional uses of vitamin B6. Br. J. Nutr. 81: 7–20, 1999.PubMedGoogle Scholar
  12. 12.
    Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. J. Am. Med. Assoc. 270: 2693–2698, 1993.CrossRefGoogle Scholar
  13. 13.
    McKinley MC, McNulty H, McPartlin J, et al. Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete. Am. J. Clin. Nutr. 73: 759–764, 2001.PubMedGoogle Scholar
  14. 14.
    Ubbink JB, van der Merwe A, Delport R, et al. The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J. Clin. Invest. 98: 177–184, 1996.PubMedCrossRefGoogle Scholar
  15. 15.
    Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ, Delport R, Potgieter HC. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J. Nutr. 124: 1927–1933, 1994.PubMedGoogle Scholar
  16. 16.
    Brattstrom L, Israelsson B, Norrving B, et al. Impaired homocysteine metabolism in early-onset cerebral and peripheral occlusive arterial disease. Effects of pyridoxine and folic acid treatment. Atherosclerosis 81: 51–60, 1990.PubMedCrossRefGoogle Scholar
  17. 17.
    Miller JW, Ribaya-Mercado JD, Russell RM, et al. Effect of vitamin B-6 deficiency on fasting plasma homocysteine concentrations. Am. J. Clin. Nutr. 55:1154–1160, 1992.PubMedGoogle Scholar
  18. 18.
    Dudman NP, Wilcken DE, Wang J, Lynch JF, Macey D, Lundberg P. Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology. Arterioscler. Thromb. 13: 1253–1260, 1993.PubMedCrossRefGoogle Scholar
  19. 19.
    Schrijver J, Speek AJ, Schreurs WH. Semi-automated fluorometric determination of pyridoxal-5′-phosphate (vitamin B6) in whole blood by high-performance liquid chromatography (HPLC). Int. J. Vitam. Nutr. Res. 51: 216–222, 1981.PubMedGoogle Scholar
  20. 20.
    Steegers-Theunissen RP, Boers GH, Steegers EA, Trijbels FJ, Thomas CM, Eskes TK. Effects of sub-50 oral contraceptives on homocysteine metabolism: a preliminary study. Contraception 45:129–139, 1992.PubMedCrossRefGoogle Scholar
  21. 21.
    Te Poele-Pothoff M, van den Berg M, Franken DG, et al. Three different methods for the determination of total homocysteine in plasma. Ann. Clin. Biochem. 32:218–220, 1995.PubMedGoogle Scholar
  22. 22.
    Benhayoun S, Adjalla C, Nicolas JP, Gueant JL, Lambert D. Method for the direct specific measurement of vitamin B12 bound to transcobalamin II in plasma. Acta Haematol 89: 195–199, 1993.PubMedCrossRefGoogle Scholar
  23. 23.
    Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat. Genet. 10: 111–113, 1995.PubMedCrossRefGoogle Scholar
  24. 24.
    Martinez M, Cuskelly GJ, Williamson J, Toth JP, Gregory JF. Vitamin B-6 deficiency in rats reduces hepatic serine hydroxymethyltransferase and cystathionine beta-synthase activities and rates of in vivo protein turnover, homocysteine remethylation and transsulfuration. J. Nutr. 130: 1115–1123, 2000.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Lydia A. Afman
    • 1
  • Nathalie M. J. van der Put
    • 1
  • Chris M. G. Thomas
    • 2
  • Frans J. M. Trijbels
    • 1
  • Henk J. Blom
    • 1
  1. 1.Department of PediatricsUniversity Medical Center NijmegenNijmegenThe Netherlands
  2. 2.Laboratory of Endocrinology and ReproductionUniversity Medical Center NijmegenNijmegenThe Netherlands

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