HOMOCYSTEINE AND NEURAL-TUBE DEFECTS

It is now well established that folic acid, when taken periconceptiona lly, can prevent many neural tube defects. It is also becoming clear t hat folic acid does not work by correcting a nutritional deficiency in pregnant women. Rather, it appears that a metabolic defect is respons ible for these neural tube defects and that this defect or defects can be corrected by a sufficiently large dose of folic acid. Our recent w ork demonstrates that homocysteine metabolism is likely to be the crit ical pathway affected by folic acid. We have demonstrated significantl y higher homocysteine levels in women carrying affected fetuses than i n control women. These findings indicate that one of the enzymes respo nsible for homocysteine metabolism is likely to be abnormal in affecte d pregnancies. Animal studies suggest that the conversion of homocyste ine to methionine could be the critical step. Rat embryos in culture r equire methionine for neural tube closure. Methionine synthase, cystat hionine synthase, and 5,10 methylene tetrahydrofolate reductase are al l important in the metabolism of homocysteine in humans. If methionine synthase is the critical enzyme, it would raise the interesting publi c health issue that vitamin B-12 might be able to stimulate the abnorm al enzyme as folic acid does. Adding vitamin B-12 might make it possib le to reduce the dose of folic acid required in fortified food, thus a llaying concerns about overexposure to folic acid.