[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

British Journal of Pharmacology

Volumn 158, Issue 8, 2009, Pages 2014-2021

  Prinz Langenohl, R ^a   Bramswig S ^a   Tobolski, O ^a   Smulders, Ym ^b   Smith, Dec ^b   Finglas, Pm ^c   Pietrzik, K ^a  

^a UNIVERSITY OF BONN   (Germany)

^b VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^c INSTITUTE OF FOOD RESEARCH   (United Kingdom)

Author keywords

6S 5 methyltetrahydrofolate; Folate derivatives; Folic acid; Humans; MTHFR polymorphism

Indexed keywords

5 METHYLTETRAHYDROFOLIC ACID; 5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); FOLIC ACID; FOLIC ACID DERIVATIVE; METAFOLIN; METHENYLTETRAHYDROFOLATE CYCLOHYDROLASE; TETRAHYDROFOLIC ACID; UNCLASSIFIED DRUG;

ABSENCE OF SIDE EFFECTS; ADULT; AREA UNDER THE CURVE; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG METABOLISM; DRUG TOLERABILITY; FEMALE; FOLIC ACID BLOOD LEVEL; GENETIC POLYMORPHISM; GENOTYPE; HOMOZYGOSITY; HUMAN; IN VIVO STUDY; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; VITAMIN SUPPLEMENTATION; WILD TYPE;

ADULT; AREA UNDER CURVE; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; FEMALE; FOLIC ACID; GENOTYPE; HUMANS; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); MUTATION; POLYMORPHISM, GENETIC; TETRAHYDROFOLATES; VITAMIN B COMPLEX;

EID: 71649105130     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2009.00492.x     Document Type: Article

References (38)

1. Brattström L, Wilcken DE, Ohrvik J, Brudin L (1998). Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis. Circulation 98: 2520 2526.
2. de Bree A, Verschuren WM, Bjorke-Monsen AL, van der Put NM, Heil SG, Trijbels FJ et al. (2003). 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 77: 687 693.
3. CDC (Centers of Disease Control) (1992). 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 41: 2 8.
4. Christensen B, Arbour L, Tran P, Leclerc D, Sabbaghian N, Platt R et al. (1999). Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects. Am J Med Genet 84: 151 157.
5. Commission of the European Communities (1993). 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.
6. Fohr I, Prinz-Langenohl R, Brönstrup A, Bohlmann AM, Nau H, Berthold HK et al. (2002). 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 75: 275 282.
7. Food and Drug Administration (1996). Food standards: amendment of standards of identity for enriched cereal grain products to require addition of folic acid. Federal Register 61: 8781 8797.
8. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG et al. (1995). A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10: 111 113.
9. Gudnason V, Stansbie D, Scott J, Bowron A, Nicaud V, Humphries S (1998). C677T (thermolabile alanine/valine) polymorphism in methylenetetrahydrofolate reductase (MTHFR): its frequency and impact on plasma homocysteine concentration in different European populations.EARS group. Atherosclerosis 136: 347 354.
10. Harmon DL, Woodside JV, Yarnell JW, McMaster D, Young IS, McCrum EE et al. (1996). The common 'thermolabile' variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia. QJM 89: 571 577.
11. Houghton LA, Sherwood KL, Pawlosky R, Ito S, O'Connor DL (2006 6S]-5-methyltetrahydrofolate is at least effective as folic acid in preventing a decline in blood folate concentrations during lactation. Am J Clin Nutr 83: 842 850.
12. Houghton LA, Yang J, O'Connor DL (2009). Unmetabolized folic acid and total folate concentrations in breast milk are unaffected by low dose folate supplements. Am J Clin Nutr 89: 216 220.
13. Kalmbach RD, Choumenkovitch SF, Troen AM, DAgostino R, Jacques PF, Selhub J (2008). Circulating folic acid in plasma: relation to folic acid fortification. Am J Clin Nutr 88: 763 768.
14. Kang SS, Zhou J, Wong PW, Kowalisyn J, Strokosch G (1988). Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet 43: 414 421.
15. Kelly P, McPartlin J, Goggins M, Weir DG, Scott JM (1997). Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. Am J Clin Nutr 65: 1790 1795.
16. Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG (2002). MTHFR 677C-T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 288: 2023 2031. (Pubitemid 35204693)
17. Koch MC, Stegmann K, Ziegler A, Schröter B, Ermert A (1998). Evaluation of the MTHFR C677T allele and the MTHFR gene locus in a German spina bifida population. Eur J Pediatr 157: 487 492.
18. Kok RM, Smith DE, Dainty JR, van den Akker JT, Finglas PM, Smulders YM et al. (2004). 5-Methyltetrahydrofolic acid and folic acid measured in plasma with liquid chromatography tandem mass spectrometry: applications to folate absorption and metabolism. Anal Biochem 326: 129 138.
19. Lamers Y, Prinz-Langenohl R, Moser R, Pietrzik K (2004). Supplementation with [6S]-5-methytetrahydrofolate or folic acid equally reduces plasma total homocysteine concentrations in healthy women. Am J Clin Nutr 79: 473 478.
20. Lamers Y, Prinz-Langenohl R, Brämswig S, Pietrzik K (2006). 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 84: 156 161.
21. Litynski P, Loehrer F, Linder L, Todesco L, Fowler B (2002). 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 32: 662 668.
22. Mader RM, Steger GG, Rizovski B, Djavanmard MP, Scheithauer W, Jakesz R et al. (1995). Stereospecific pharmacokinetics of rac-5-methyltetrahydrofolic acid in patients with advanced colorectal cancer. Br J Clin Pharmacol 40: 209 215.
23. Meisel C, Cascorbi I, Gerloff T, Stangl V, Laule M, Müller JM et al. (2001). Identification of six methylenetetrahydrofolate reductase (MTHFR) genotypes resulting from common polymorphisms: impact on plasma homocysteine levels and development of coronary artery disease. Atherosclerosis 154: 651 658.
24. Meleady R, Ueland PM, Blom H, Whitehead AS, Refsum H, Daly LE et al. (2003). Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: the European Concerted Action Project. Am J Clin Nutr 77: 63 70.
25. Molloy AM, Daly S, Mills JL, Kirke PN, Whitehead AS, Ramsbottom D et al. (1997). Thermolabile variant of 5,10-methylenetetrahydrofolate reductase asssociated with low red-cell folates: implications for folate intake recommendations. Lancet 349: 1591 1593.
26. Ou CY, Stevenson RE, Brown VK, Schwartz CE, Allen WP, Khoury MJ et al 1996). 5, 10-Methylenetetrahydrofolate reductase genetic polymorphism as a risk factor for neural tube defects. Am J Med Genet 63: 610 614.
27. Pentieva K, McNulty H, Reichert R, Ward M, Strain JJ, McKillop DJ et al. (2004). The short-term bioavailablities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men. J Nutr 134: 580 585.
28. Prinz-Langenohl R, Brönstrup A, Thorand B, Hages M, Pietrzik K (1999). Availability of food folate in humans. J Nutr 129: 913 916.
29. Prinz-Langenohl R, Lamers Y, Moser R, Pietrzik K (2003). Effect of folic acid preload on the bioavailability of [6S]-5-methyltetrahydrofolate and folic acid in healthy volunteers [Abstract J Inherit Metab Dis 26: 124.
30. Scholl TO, Johnson WG (2000). Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr 71 (Suppl. 1295S 1303S.
31. Shields DC, Kirke PN, Mills JL, Ramsbottom D, Molloy AM, Burke H (1999). 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 64: 1045 1055.
32. Smith AD, Kim Y-I, Refsum H (2008). Is folic acid good for everyone? Am J Clin Nutr 87: 517 533.
33. Troen AM, Mitchell B, Sorensen B, Wener MH, Johnston A, Wood B et al. (2006). Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr 136: 189 194.
34. van der Put NMJ, Blom HJ (2000). Neural tube defects and a disturbed folate dependent homocysteine metabolism. Eur J Obstet Gynecol Reprod Biol 92: 57 61.
35. Venn BJ, Green TJ, Moser R, McKenzie JE, Skeaff M, Mann J (2002). Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid. J Nutr 132: 3353 3355.
36. Whitehead AS, Gallagher P, Mills JL, Kirke PN, Burke H, Molloy AM et al. (1995). A genetic defect in 5,10 methylenetetrahydrofolate reductase in neural tube defects. QJM 88: 763 766.
37. Willems FF, Boers GHJ, Blom HJ, Aengevaeren WRM, Verheugt FWA (2004). Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease. Br J Pharmacol 141: 825 830.
38. Wright AJ, Dainty JR, Finglas PM (2007). Folic acid metabolism in humans revisited: potential implications for proposed mandatory folic acid fortification in the UK. Br J Nutr 98: 667 675.