Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
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Effect of Folic Acid Supplementation on Serum Homocysteine and B Vitamins in Infertile Women

불임여성에서 엽산 보충이 혈중 호모시스테인과 비타민 B 수준에 미치는 영향

  • Eom Hyeajin (Department of Food and Nutritional Sciences, Asia Food & Nutrition Research Institute, Ewha Womans University) ;
  • Kim Ki Nam (Department of Food and Nutritional Sciences, Asia Food & Nutrition Research Institute, Ewha Womans University) ;
  • Chang Namsoo (Department of Food and Nutritional Sciences, Asia Food & Nutrition Research Institute, Ewha Womans University)
  • 엄혜진 (이화여자대학교 생활환경대학 식품영양학과, 아시아식품영양연구소) ;
  • 김기남 (이화여자대학교 생활환경대학 식품영양학과, 아시아식품영양연구소) ;
  • 장남수 (이화여자대학교 생활환경대학 식품영양학과, 아시아식품영양연구소)
  • Published : 2005.04.01
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Abstract

Elevated homocysteine concentration is known to be related to placental abruption, spontaneous abortion, and many adverse pregnancy outcomes. The purpose of this study was to investigate the effects of folic acid supplementation ($1000{\cal}ug$ per day) and 5, 10 methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism genotype on serum homocysteine and B vitamin levels in 50 infertile women ($31.2{\pm}3.2\;years$). Blood sampling was performed at baseline and at the end of folic acid supplementation period. In infertile women, serum folate and vitamin $B_{12}$ concentrations were significantly higher in post-supplementation than those in pre-supplementation. Serum homocysteine concentration was significantly lower in post-supplementation than that in pre-supplementation. However, serum homocysteine levels were still higher in the T/T genotype than those in the C/C or C/T even after folic acid supplementation. Serum homo-cysteine was inversely related to serum folate in T/T homozygotes at baseline and at the end of folic acid supplementation. These results suggest that folic acid supplementation is needed for infertile women to improve their vitamin status and also to reduce the risk of hyperhomocysteinemia. These effects were different according to their MTHFR C677T genotypes. Therefore, further studies are necessary to determine the optimal level of supplementation of folic acid by MTHFR genotypes.

Keywords

References

  1. Woods NF, Fogel CI. Health Care of Woman: A Nursing Perspective St. Louis: The CV Mosby Company, pp.257-283, 1981
  2. Korea Institute for Health and Social Affairs. Gevemment responses in pursuit of population policy: Preparing for low fertility. Policy Paper 193: 2001-2013, 2003
  3. Burke G, Robinson K, Refsum H, Stuart B, Drumm J, Graham I. Intrauterine growth retardation, perinatal death, and maternal homocysteine levels. N Engl J Ned 326: 69-70, 1992
  4. Vollset SE, Refsum H, Irgens LM, Emblem BM, Tverdal A, Gjessing HK, Monsen ALB, Ueland PM. Plasma total homocysteine, pregnancy complications and adverse pregnancy outcomes: the Hordaland Homocysteine Study. Am J Clin Nutr 71: 962-968, 2000 https://doi.org/10.1093/ajcn/71.4.962
  5. Mill JL, McPartlin JM, Kirke PN. Homocysteine metabolism in pregnancies complicated by neural tube defects. Lancet 345: 149-151, 1995 https://doi.org/10.1016/S0140-6736(95)90165-5
  6. Rosenquist TH, Ratashak SA, Selhub J. Homocysteine induces congenital defects of the heart and neural tube: effect of folic acid. Pro Natl Acad Sci USA 93: 15227-15232, 1995
  7. Wouters MG, Boers GH, Blom HJ, Trijbels FJ, Thomas CM, Bonn GP, Steegers-Theunissen RP, Eskes TK. Hyperhomocysteinemia: a risk factor in women with unexplained recurrent early pregnancy loss. Fertil Steril 60: 820-825, 1993 https://doi.org/10.1016/S0015-0282(16)56282-7
  8. Goddijn- Wessel TAW, Wouters MGAJ, Molen EF, Spuijbroek M, Blom HJ, Boers G, Eskes TKAB. Hyperhomocysteinemia: a risk factor for placental abruption or infartion. Eur J Obstet Gynecol 66: 23-29, 1996 https://doi.org/10.1016/0301-2115(96)02383-4
  9. Nelen WLDM, Blom HJ, Thomas CMG, Steegers EAP, Boers GHJ, Eskes TKAB. Methylenetetrahydrofolate reductase polymorphism affects the change in homocysteine and folate concentrations resulting from low dose folic acid supplementation in women with unexplained recurrent miscarriages. J Nutr 128: 1336-1341, 1998
  10. Owen EP, Human L, Carolissen AA, Harley EH, Odndaal HJ. Hyperhomocysteinernia-A risk factor for abruptio placentae. J Inher Metab Dis 20: 369-362, 1997
  11. Power RW, Minich LA, Lykins DL, Ness RB, Cromblenholme WR, Roberts JM. Methylenetetrahydrofolate reductase polymorphism, folate, and susceptibility to preeclampsia. J Soc Gynecol Invest 6: 74-79, 1999 https://doi.org/10.1016/S1071-5576(98)00052-5
  12. Mason JB. Biomarkers of nutrient exposure and status in onecarbon (Methyl) metabolism. J Nutr 133: 941S-947S, 2003 https://doi.org/10.1093/jn/133.3.941S
  13. Shils ME, Olson JA, Shike M, Ross AC. Choline and phosphatidylcholine. In: Mordem Nutrition in Health and Disease, 9th Ed. Williams & Wilkins, Baltimore, MD, p.514, 1998
  14. Kang SS, Wong PWK, Cook HY, Norusis M, Messer N. Protein-bound homocyst (e)ine. J Clin Invest 77: 1482-1286, 1986
  15. Ueland PM, Hustad S, Schneede J, Refsum H, Vollset SE. Biological and clinical implications of the MTHFR C677T poly-morphism. Trends in Pharmacol Sci 22: 195-201, 2002
  16. Oh JS, Jung HJ, Kwon HC, Pack WI, Koong MK, Kim WY. Dietary behavior of infertile women in korea. Kor J Fertil Steril 30(4): 341-350, 2003
  17. Lim MY, Nam YS, Kim SS, Chang NS. Vitamin B status and serum homocysteine levels in infertile women. Kor J Nutr 37 (2) : 115-122, 2004
  18. Park KS, Podskarbi T, Yoo EA, Shin YS. The C677T mutation in the methylenetetrahydrofolate reductase gene in Koreans. Korean J Genetics 20 (1) : 23-28, 1998
  19. Kim NK, Kang GD, Kim HJ, Kim JH, Nam YS, Lee S, Chung HM, Kang SH, Ahn JY, Choi BO, Hwang SG, Oh D. Genetic polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T and AI298C in healthy. Korean J Genetics 24 (2) : 227-234, 2002
  20. Nam YS, Choi JS, Ha KS, Lee JW, Oh DY. The analysis of interrelationship between homocysteine and methylenetetrahydrofolate reductase mutation in patients with recurrent spontaneous abortion. Kor Soc Fertil Steril 29 (3): 1-9, 2003
  21. Capo-Chichi CD, Gueant JL, Lefebvre E, Bennani N, Lorentz E, Vidailhet C, Vidailhet M. Riboflavin and riboflavin-derived cofactors in adolescent girls with anorexia nervosa. Am J Clin Nutr 69: 672-678, 1999 https://doi.org/10.1093/ajcn/69.4.672
  22. Araki A, Sako Y. Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromato 422: 43-52, 1987 https://doi.org/10.1016/0378-4347(87)80438-3
  23. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard C, Matthews R, Boers GJ, den Heijer M, Kluijtmans LA, van den Heuvel LP, Rozen RA. Candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10: 111-113, 1995 https://doi.org/10.1038/ng0595-111
  24. Wouters MG, Boers GH, Blom HJ, Trijbels FJ, Thomas CM, Borm GF, Steegers-Theunissen RP, Eskes TK. Hyperhornocysteinemia: a risk factor in women with unexplained recurrent early pregnancy loss. Fertil Steril 60: 820-825, 1993 https://doi.org/10.1016/S0015-0282(16)56282-7
  25. Van der Molen EF, Nelen WLD, Heil SG, Eskes TKA, Blom HJ. The mutation 677C${\rightarrow}$T of the methylenetetrahydrofolate reductase (MTHFR) gene as a possible risk factor for placental vasculopathy. Neth J Med 52: 28, 1998
  26. Quere I, Bellet H, Hoffet M, Janbon C, Mares P, Gris JC. A woman with five consecutive fetal deaths: case report and retrospective analysis of hyperhomocysteinemia prevalence in 100 consecutive women with recurrent miscarriages. Fertil Steril 69 (1) : 152-154, 1998 https://doi.org/10.1016/S0015-0282(97)00451-2
  27. Kupfermine MJ, Eldor A, Steinman N, Many A, Bar-Am A, Jaffa A, Faith G, Lessing JB. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med 340: 9-13, 1999 https://doi.org/10.1056/NEJM199901073400102
  28. Jacques PF, Bostom AG, William RR, Ellison C, Eckfeldt JH, Rosenburs IH, SeIhub J, Rozen R. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 93: 7-9, 1996 https://doi.org/10.1161/01.CIR.93.1.7
  29. Gudnason V, Stansble D, Scott J, Browron A, Nicaud V, Humphries S. C677T (thermolable alanine/valine) polymorphism in methylenetetrahydrofolate reductase (MTHFR): Its frequency and impact on plasm homocysteine concentration in different Euro-pean population. Atherosclerosis 136: 347-354, 1998 https://doi.org/10.1016/S0021-9150(97)00237-2
  30. Kim KN, Kim YJ, Chang N. The interaction of the 5, 10-methylenetetrahydrofolate reductase (MTHFR) polymorphism with folate and vitamin $B_{12}$ intakes and serum homocysteine concentrations in pregnant women. Kor J Nutr 35 (10) : 1045-1052, 2002
  31. Sutterlin M, Bussen S, Ruppert D, Steck T. Serum levels of folate and cobalamin in women with recurrent spontaneous abortion. Human Reproduction 12(10): 2292-2296, 1997 https://doi.org/10.1093/humrep/12.10.2292
  32. Lussier-Cacan S, Xhignesse M, Piolot A, Selhub J, Davignon J, Genest J Jr. Plasma total homocysteine in healthy subjects: sex-specific relation with biological traits. Am J Clin Nutr 64: 587-594, 1996 https://doi.org/10.1093/ajcn/64.4.587
  33. Skoupy S, Fodinger M, Veitl M, Perschl A, Puttinger H, Rohrer C, Schindler K, Vychytil A, Hod WH, Sunder-Plassmann G. Riboflavin is a determinant of total homocysteine plasma concentrations in end-stage renal disease patients. J Am Soc Nephrol 13: 1331-1337, 2002 https://doi.org/10.1097/01.ASN.0000013299.11876.F6