Methylenetetrahydrofolate Reductase Polymorphism Affects the Change in Homocysteine and Folate Concentrations Resulting from Low Dose Folic Acid Supplementation in Women with Unexplained Recurrent Miscarriages

Manuscript received 27 January 1998. Initial reviews completed 20 February 1998. Revision accepted 30 March 1998.

Willianne L.D.M. Nelen, Henk J. Blom^*, Chris M. G. Thomas, Eric A. P. Steegers,, Godfried H. J. Boers, and Tom K.A.B. Eskes

Department of Obstetrics and Gynecology, ^* Pediatrics and  Internal Medicine, University Hospital Nijmegen St Radboud, 6500 HB Nijmegen, The Netherlands

To determine the effects of daily supplementation of 0.5 mg folic acid on homocysteine and folate concentrations, we investigated 49 women with a history of unexplained recurrent miscarriages. A methionine loading test (including the vitamin concentrations of concern) was used preceding and after 2 mo of folic acid intake. Subsequently, these effects were studied after stratification for C677T 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism. Folic acid supplementation (for 2 mo) reduced the median fasting and delta (after-load minus fasting) total plasma homocysteine (tHcy) concentrations 27% (P < 0.001) and 14% (P < 0.05), respectively. Median serum and red cell folate concentrations increased 275 and 70%, respectively (P < 0.01). The homocysteine-lowering effect was most marked in women with the highest tHcy concentrations at baseline. All MTHFR-genotypes (homozygous T/T, n = 8; heterozygous T/C, n = 23; wild type C/C, n = 18) had a different response to the supplementation. After 2 mo, homozygous women showed the greatest decline in median fasting (41%; P < 0.01) tHcy concentrations, but the lowest absolute increase in serum folate concentration (+26 nmol/L; P < 0.05). In conclusion, 2 mo of daily supplementation of 0.5 mg folic acid in women with a history of unexplained recurrent miscarriages caused, in general, substantially reduced tHcy concentrations. This effect was most distinct in women with the highest tHcy concentrations at baseline and in women homozygous for the 677 CT mutation of the MTHFR-gene.

The Journal of Nutrition Vol. 128 No. 8 August 1998, pp. 1336-1341
Copyright ©1998 by the American Society for Nutritional Sciences

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