RSS-Feed abonnieren
DOI: 10.1055/s-2000-12953
Georg Thieme Verlag Stuttgart · New York
Homocysteine Metabolism and Effects of Folic Acid Supplementation in Patients Affected with Spina Bifida
Publikationsverlauf
Publikationsdatum:
31. Dezember 2000 (online)
Folic acid supplementation around conception decreases the risk of having offspring with a neural tube defect. However, the aetiology is often still unknown. This study investigated whether spina bifida patients have lower blood folate and higher fasting and post-methionine-load plasma total homocysteine (tHcy) concentrations than control patients. Moreover, the effects of supplementation with 500 µg folic acid/d on folate and tHcy concentrations were determined. Spina bifida patients (n = 12) and disabled control patients (n = 15) received 4 weeks of placebo treatment followed by 4 weeks of intervention with 500 µg folic acid/d. Blood was collected at the start and after 4 and 8 weeks. A methionine-loading test was performed at the start and the end of the study. At baseline, no significant differences occurred between spina bifida and control patients. Folic acid supplementation significantly increased plasma and red blood cell folate concentrations in both groups. Folic acid decreased fasting tHcy concentrations in control patients by 1.6 ± 0.5 µmol/l (p < 0.01) and in spina bifida patients by 2.2 ± 1.3 µmol/l (p = 0.10). This study does not show a derangement in homocysteine metabolism in spina bifida compared to control patients. Moreover, folic acid supplementation seems at least as effective in spina bifida patients as in controls.
Key words
Spina bifida - Homocysteine - Folate - Folic acid
References
- 1 Bjørke-Monsen A L, Ueland P M, Schneede J, Vollset S E, Refsum H. Elevated plasma total homocysteine and C677 T mutation of the methylenetetrahydrofolate reductase gene in patients with spina bifida. QJM. 1997; 90 593-596
- 2 Brouwer I A, van Dusseldorp M, Thomas C MG. et al . Low-dose folic acid supplementation decreases plasma homocysteine: a randomized trial. Am J Clin Nutr. 1999; 69 99-104
- 3 Bunduki V, Dommergues M, Zittoun J, Marquet J, Muller F, Dumez Y. Maternal-fetal folate status and neural tube defects: a case control study. Biol Neonate. 1995; 67 154-159
- 4 Centers for Disease Control . Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. Morbid Mortal Weekly Rep. 1992; 41 1-7
- 5 Czeizel A E, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992; 327 1832-1835
- 6 den Heijer M, Brouwer I A, Bos G J. et al . Vitamin supplementation reduces blood homocysteine levels - A controlled trial in patients with venous thrombosis and healthy volunteers. Arterioscler Thromb Vasc Biol. 1998; 18 356-361
- 7 Dierkes J, Kroesen M, Pietrzik K. Folic acid and vitamin B6 supplementation and plasma homocysteine concentrations in healthy young women. Internat J Vit Res. 1998; 82 98-103
- 8 Economides D L, Ferguson J, Mackenzie I Z, Darley J, Ware I I, Holmes-Siedle M. Folate and vitamin B12 concentrations in maternal and fetal blood, and amniotic fluid in second trimester pregnancies complicated by neural tube defects. Br J Obstet Gynaecol. 1992; 99 23-25
- 9 Expert Advisory Group .Folic Acid and the Prevention of Neural Tube Defects. London; Department of Health 1992
- 10 Fiskerstrand T, Refsum H, Kvalheim G, Ueland P M. Homocysteine and other thiols in plasma and urine: automated determination and sample stability. Clin Chem. 1993; 39 263-271
- 11 Frosst P, Blom H J, Milos R. et al . A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase [letter]. Nat Genet. 1995; 10 111-113
- 12 Gardiki-Kouidou P, Seller M J. Amniotic fluid folate, vitamin B12 and transcobalamin in neural tube defects. Clin Genet. 1997; 33 441-448
- 13 Koch M C, Stegmann K, Ziegler A, Schroter B, Ermert A. Evaluation of the MTHFR C677 T allele and the MTHFR gene locus in a German spina bifida population. Eur J Pediatr. 1998; 157 487-492
- 14 Vitamin Study Research Group M RC. Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study. Lancet. 1991; 338 131-137
- 15 Schrijver J, Speek A J, Schreurs W HP. Semi-automated fluorimetric determination of pyridoxal-5′-phosphate (vitamin B6) in whole blood by high-performance liquid chromatography (HPLC). Intern J Vitamin and Nutrition Res. 1981; 51 216-222
- 16 Steegers-Theunissen R PM, Boers G H, Trijbels F J. et al . Maternal hyperhomocysteinemia: a risk factor for neural-tube defects?. Metabolism. 1994; 43 1475-1480
- 17 Steegers-Theunissen R PM, Boers G H, Blom H J. et al . Neural tube defects and elevated homocysteine levels in amniotic fluid. Am J Obstet Gynecol. 1995; 172 1436-1441
- 18 te Poele-Pothoff M T, van den Berg M, Franken D G. et al . Three different methods for the determination of total homocysteine in plasma. Ann Clin Biochem. 1995; 32 218-220
- 19 Thorand B, Pietrzik K, Prinz L R, Hages M, Holzgreve W. Maternal and fetal serum and red blood cell folate and vitamin B12 concentrations in pregnancies affected by neural tube defects. Z Geburtshilfe Neonatol. 1996; 200 176-180
- 20 Department of Health and Human Services U S. Food and Drug Administration. Food standards: amendment of the standards of identity for enriched grain products to require addition of folic acid. Fed Regist. 1996; 61 8781-8807
- 21 van der Put N MJ, Eskes T KAB, Blom H J. Is the common 677 C - T mutation in the methylenetetrahydrafolate reductase gene a risk factor for neural tube defects? A meta-analysis. QJM. 1997; 90 111-115
- 22 van der Put N MJ, Steegers-Theunissen R PM, Frosst P. et al . Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet. 1995; 346 1070-1071
- 23 van der Put N MJ, Thomas C MG, Eskes T KAB. et al . Altered folate and vitamin B12 metabolism in families with spina bifida offspring. QJM. 1997; 90 505-510
- 24 Ward M, McNulty H, McPartlin J, Strain J J, Weir D G, Scott J M. Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid. QJM. 1997; 90 519-524
- 25 Weekes E W, Tamura T, Davis R O. et al . Nutrient levels in amniotic fluid from women with normal and neural tube defect pregnancies. Biol Neonate. 1992; 61 226-231
- 26 Whitehead A S, Gallagher P, Mills J L. et al . A genetic defect in 5, 10-methylenetetrahydrofolate reductase in neural tube defects. QJM. 1995; 88 763-766
Régine Steegers-Theunissen
Department of Obstetrics and Gynaecology University Hospital St. Radboud Nijmegen
P. O. Box 9101
6500 HB Nijmegen
The Netherlands
eMail: r.steegers@MIE.KUN.NL