Previous work on neural tube defects, associated with the MTHFR 677T allele has shown that higher dose folic acid supplementation may help to overcome the pharmacogenetic reduction in the formation of the active form of folic acid (5 methyl folate) that is necessary as part of one carbon metabolism.15 Thus, we hypothesized that folate administration would result in a slight reduction in metabolic measures with either the MTHFR 677T allele or COMT 158 Val allele would show the greatest improvements, given that they would have stronger responses to the pharmacologically induced drive. This evidence concerns the gene MTHFR and isolated spina bifida.