Folic Acid and Prevention of Spina Bifida

Norman W. Klein, PhD
JAMA. 1996;275(21):1636. doi:10.1001/jama.1996.03530450026020.
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To the Editor.  —In their Editorial, Dr Oakley and colleagues1 failed to address the mechanisms by which folic acid acts to close neural tubes. Oakley and colleagues note that folic acid supplements may reduce the levels of circulating homocysteine, a substance that may be involved in vascular disease, but they failed to mention that with the methyl group from folic acid, homocysteine becomes methionine. This essential amino acid has been recognized not only as a normal constituent of proteins, but also as one that plays a key role in cellular methylation reactions as the most immediate precursor of S-adenoylmethionine. A considerable amount of experimental evidence now exists showing that methionine supplements allowed neural tube closure to be completed under conditions of nutritional deficiencies, 2,3 the presence of the human teratogen valproic acid, 4 and in the presence of a genetic mutation that caused neural tube defects (NTDs).5


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