У женщин с полиморфизмом гена метилентетрагидрофолатредуктазы 677C → Т по гомозиготному или “дикому” типу [6S]-5-метилтетрагидрофолат повышает уровень фолатов в плазме крови больше, чем фолиевая кислота


Р. Принц-Лангехоль (1), С. Брэмсвиг (1), О. Тобольски (1), У.М. Смульдерс (2), Д.Е.Ц. Смит (2), П.М. Финглас (3), Л. Пьетрцик (1)

1 Университет в Бонне, Германия; 2 Медицинский центр, Амстердам, Нидерланды; 3 Институт исследования проблем питания, Норвик, Великобритания
У женщин с полиморфизмом гена метилентетрагидрофолатредуктазы 677C ? Т по гомозиготному или “дикому” типу [6S]-5-метилтетрагидрофолат повышает уровень фолатов в плазме крови больше, чем фолиевая кислота
Фолиевую кислоту (ФК) в дозировке порядка 400 мг/день рекомендуют всем женщинам репродуктивного возраста в качестве меры первичной профилактики развития дефектов нервной трубки у будущего потомства. В рандомизированном двойном слепом перекрестном клиническом исследовании, включившем клинически здоровых женщин с мутацией гена 5,10-метилентетрагидрофолатредуктазы (полиморфизм 677С ? Т) по генотипу ТТ или СС, показано, что при назначении на непродолжительный срок в физиологической дозировке пищевая добавка [6S]-5-метилтетрагидрофолат ([6S]-5-МТГФ) в большей степени, чем ФК, способствует повышению уровня фолатов в плазме крови вне зависимости от генотипа мутации. Поскольку о наличии у [6S]-5-МТГФ серьезных побочных эффектов ничего не известно, препараты на основе этой природной биологически активной формы фолатов могут выступать в качестве альтернативы добавкам с ФК.

Литература


1. Brattstrom 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 WklyRep 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, Bronstrup A, et al. 5,10-methylenetetrahydrofolate reductase genotype determines the plasma homocysteinelowering 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. Atherosclerosis1998;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 Nutr2008;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;79:473–78.


21. Lamers Y, Prinz-Langenohl R, Bramswig 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 ClinNutr 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 Pharmacol1995;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, Bronstrup 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 InheritMetab Dis 2003;26:124.


31. Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr2000;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 Nutr2006;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 Biol2000;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 Nutr2002;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 utilization of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease. Br JPharmacol 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.


Похожие статьи


Бионика Медиа