[6S]-5-METHYLTETRAHYDROFOLATE INCREASES PLASMA FOLATE MORE EFFECTIVELY THAN FOLIC ACID IN WOMEN WITH THE HOMOZYGOUS OR WILD-TYPE 677C,T POLYMORPHISM OF METHYLENETETRAHYDROFOLATE REDUCTASE *


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Abstract

Folic acid (FA) at a dosage of 400 mg/day is recommended for all women of reproductive age as a measure for primary prevention of neural tube defects in future offspring. Randomized double-blind, crossover clinical study, including apparently healthy women with 5,10-methylenetetrahydrofolate reductase (677S → T polymorphism) gen mutation in the TT or CC genotype, has shown that the appointment of supplement [6S] -5 -methyltetrahydrofolate ([6S]-5-MTHF) in physiological doses for a short period increases plasma folate more effectively than FA, regardless of the genotype of the mutation. There is no information about serious side effects of a [6S]-5-MTHF, hence, preparations based on this natural biologically active form of folate can be considered as an alternative to FA.

References

  1. Brattström L, Wilcken DE, Ohrvik J, Brudin L. Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a metaanalysis. Circulation 1998;98:2520-56.
  2. Prinz-Langenohl R, et al. 5-MTHF and FA supplementation and plasma folate. Br J Pharmacol 2009;158:2014-21.
  3. de Bree A, Verschuren WM, Bjorke-Monsen AL, et al. Effect of the methylenetetrahydrofolate reductase 677C→T mutation on the relations among folate intake and plasma folate and homocysteine concentrations in a general population sample. Am J Clin Nutr 2003;77:687-93.
  4. CDC (Centers of Disease Control). Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. Morb Mortal Wkly Rep 1992;41:2-8.
  5. Christensen B, Arbour L, Tran P, et al. Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects. Am J Med Genet 1999;84:151-57.
  6. Commission of the European Communities. Nutrient and energy intakes for the European Community. Office for the Official Publications of the European Communities. Reports of the Scientific Committees for Food: 31st series. Luxembourg 1993.
  7. Fohr I, Prinz-Langenohl R, Brönstrup A, et al. 5,10-methylenetetrahydrofolate reductase genotype determines the plasma homocysteine-lowering effect of supplementation with 5-methyltetrahydrofolate or folic acid in healthy young women. Am J Clin Nutr 2002;75:275-82.
  8. Food and Drug Administration. Food standards: amendment of standards of identity for enriched cereal grain products to require addition of folic acid. Federal Register 1996;61:8781-97.
  9. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995;10:111-13.
  10. Gudnason V, Stansbie D, Scott J, et al. C677T (thermolabile alanine/valine) polymorphism in methylenetetrahydrofolate reductase (MTHFR): its frequency and impact on plasma homocysteine concentration in different European populations. EARS group. Atherosclerosis 1998;136:347-54.
  11. Harmon DL, Woodside JV, Yarnell JW, et al. The common "thermolabile" variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia. QJM 1996;89:571-77.
  12. Houghton LA, Sherwood KL, Pawlosky R, et al. [6S]-5-methyltetrahydrofolate is at least effective as folic acid in preventing a decline in blood folate concentrations during lactation. Am J Clin Nutr 2006;83:842-50.
  13. Houghton LA, Yang J, O'Connor DL. Unmetabolized folic acid and total folate concentrations in breast milk are unaffected by low dose folate supplements. Am J Clin Nutr 2009;989:216-20.
  14. Kalmbach RD, Choumenkovitch SF, Troen AM, et al. Circulating folic acid in plasma: relation to folic acid fortification. Am J Clin Nutr 2008;88:763-68.
  15. Kang SS, Zhou J, Wong PW, et al. Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet 1988;43:414-21.
  16. Kelly P, McPartlin J, Goggins M, et al. Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. Am J Clin Nutr 1997;65:1790-95.
  17. Klerk M, Verhoef P, Clarke R, et al. MTHFR 677C-T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 2002;288:2023-31.
  18. Koch MC, Stegmann K, Ziegler A, et al. Evaluation of the MTHFR C677T allele and the MTHFR gene locus in a German spina bifida population. Eur J Pediatr 1998;157:487-92.
  19. Kok RM, Smith DE, Dainty JR, et al. 5-Methyltetrahydrofolic acid and folic acid measured in plasma with liquid chromatography tandem mass spectrometry: applications to folate absorption and metabolism. Anal Biochem 2004;326:129-38.
  20. Lamers Y, Prinz-Langenohl R, Moser R, Pietrzik K. Supplementation with [6S]-5-methytetrahydrofolate or folic acid equally reduces plasma total homocysteine concentrations in healthy women. Am J Clin Nutr 2004;79:473-8.
  21. Lamers Y, Prinz-Langenohl R, Brämswig S, Pietrzik K. Red blood cell folate concentrations increase more after supplementation with [6S]-5-methytetrahydrofolate than with folic acid in women of childbearing age. Am J Clin Nutr 2006;84:156-61.
  22. Litynski P, Loehrer F, Linder L, et al. Effect of low dose of 5-methyltetrahydrofolate and folic acid on plasma homocysteine in healthy subjects with or without the 677C→T polymorphism of methylenetetrahydrofolate reductase. Eur J Clin Invest 2002;32:662-68.
  23. Mader RM, Steger GG, Rizovski B, et al. Stereospecific pharmacokinetics of rac-5-methyltetrahydrofolic acid in patients with advanced colorectal cancer. Br J Clin Pharmacol 1995;40:209-15.
  24. Meisel C, Cascorbi I, Gerloff T, et al. Identification of six methylenetetrahydrofolate reductase (MTHFR) genotypes resulting from common polymorphisms: impact on plasma homocysteine levels and development of coronary artery disease. Atherosclerosis 2001;154:651-58.
  25. Meleady R, Ueland PM, Blom H, et al. Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: the European Concerted Action Project. Am J Clin Nutr 2003;77:63-70.
  26. Molloy AM, Daly S, Mills JL, et al. Thermolabile variant of 5,10-methylenetetrahydrofolate reductase asssociated with low red-cell folates: implications for folate intake recommendations. Lancet 1997;349:1591-93.
  27. Ou CY, Stevenson RE, Brown VK, et al. 5, 10-Methylenetetrahydrofolate reductase genetic polymorphism as a risk factor for neural tube defects. Am J Med Genet 1996;63:610-14.
  28. Pentieva K, McNulty H, Reichert R, et al. The short-term bioavailablities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men. J Nutr 2004;134:580-85.
  29. Prinz-Langenohl R, Brönstrup A, Thorand B, et al. Availability of food folate in humans. J Nutr 1999;129:913-16.
  30. Prinz-Langenohl R, Lamers Y, Moser R, Pietrzik K. Effect of folic acid preload on the bioavailability of [6S]-5-methyltetrahydrofolate and folic acid in healthy volunteers [Abstract]. J Inherit Metab Dis 2003;26:124.
  31. Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr 2000;71:1295S-1303S.
  32. Shields DC, Kirke PN, Mills JL, et al. The "thermolabile" variant of methylenetetrahydrofolate reductase and neural tube defects: An evaluation of genetic risk and the relative importance of the genotypes of the embryo and the mother. Am J Hum Genet 1999;64:1045-55.
  33. Smith AD, Kim Y-I, Refsum H. Is folic acid good for everyone? Am J Clin Nutr 2008;87:517-33.
  34. Troen AM, Mitchell B, Sorensen B, et al. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr 2006;136:189-94.
  35. van der Put NMJ, Blom HJ. Neural tube defects and a disturbed folate dependent homocysteine metabolism. Eur J Obstet Gynecol Reprod Biol 2000;92:57-61.
  36. Venn BJ, Green TJ, Moser R, et al. Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid. J Nutr 2002;132:3353-55.
  37. Whitehead AS, Gallagher P, Mills JL, et al. A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube defects. QJM 1995;88:763-66.
  38. Willems FF, Boers GHJ, Blom HJ, et al. Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease. Br J Pharmacol 2004;141:825-30.
  39. Wright AJ, Dainty JR, Finglas PM. Folic acid metabolism in humans revisited: potential implications for proposed mandatory folic acid fortification in the UK. Br J Nutr 2007;98: 667-75.

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