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ARTICLE |

Folic Acid and Prevention of Spina Bifida FREE

Norman W. Klein, PhD
JAMA. 1996;275(21):1636-1636. 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

REFERENCES

Oakley GP, Erickson JD, Adams MJ.  Urgent need to increase folic acid consumption. JAMA . 1995;;274:1717-1718.
Chatot CL, Klein NW, Clapper ML, et al.  Human serum teratogenicity studied by rat embryo culture: epilepsy, anticonvulsant drugs and nutrition. Epilepsia . 1984;;25:205-216.
Ferrari DA, Gilles PA, Klein NW, et al.  Rat embryo development on human sera is related to numbers of previous spontaneous abortions and nutritional factors. Am J Obstet Gynecol . 1994;;170:228-236.
Ehlers K, Elmazar MMA, Nau H.  Methionine reduces the valproic acid-induced spina bifida rate in mice without altering valproic acid kinetics. J Nutr . 1996;;126:67-75.
Essien FB, Wannberg SI.  Methionine but not folinic acid or vitamin B-12 alters the frequency of neural tube defects in Axd mutant mice. J Nutr . 1993;;123:27-34.
Moephuli SR, Klein NW.  Identification of proteins methylated prior to neural tube closure. Mol Biol Cell . 1995;;6:325a.

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Oakley GP, Erickson JD, Adams MJ.  Urgent need to increase folic acid consumption. JAMA . 1995;;274:1717-1718.
Chatot CL, Klein NW, Clapper ML, et al.  Human serum teratogenicity studied by rat embryo culture: epilepsy, anticonvulsant drugs and nutrition. Epilepsia . 1984;;25:205-216.
Ferrari DA, Gilles PA, Klein NW, et al.  Rat embryo development on human sera is related to numbers of previous spontaneous abortions and nutritional factors. Am J Obstet Gynecol . 1994;;170:228-236.
Ehlers K, Elmazar MMA, Nau H.  Methionine reduces the valproic acid-induced spina bifida rate in mice without altering valproic acid kinetics. J Nutr . 1996;;126:67-75.
Essien FB, Wannberg SI.  Methionine but not folinic acid or vitamin B-12 alters the frequency of neural tube defects in Axd mutant mice. J Nutr . 1993;;123:27-34.
Moephuli SR, Klein NW.  Identification of proteins methylated prior to neural tube closure. Mol Biol Cell . 1995;;6:325a.
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