Neural tube defects folate mechanisms

The mechanism by which dietary folate supplementation prevents NTDs is not understood (Prevention of Neural Tube Defects Results of... 

A number of mechanisms have been proposed to account for the role of folate in the development of neural tube defects (Moyers and Bailey, 2001) ... 

The risk of foetal malformation is increased in women with epilepsy compared with the general population. Minor dysmorphic features are most frequent, but more severe forms such as facial clefts and neural tube defects are not uncommon. The two major forms of neural tube defects are (i) anence-phaly, a lethal malformation, and (ii) spina bifida—a closure defect in the spinal eolumn that may lead to paralysis of the lower limbs. The rates of malformations are about 3% with CBZ and lamotrigine (LTG), 7% with VPA, and 15% with combinations of two or more AEDs. It is probable that AEDs have several different teratogenic mechanisms. Low folate levels appear to be associated with increased risks of foetal malformations in women on AEDs. Furthermore, it has been suggested that maternal C677T MTHFR polymorphism or some abnormality related to methionine synthetase increase the risk of foetal malformation in patients on AEDs (Mills et al. 1995). 

The mechanisms by which vitamins prevent illnesses are not weU understood, and the amounts needed to lower risks for certain disease conditions may be higher than the current recommended levels for preventing nutritional deficiencies. For example, the Institute of Medicine recommends that to prevent neural tube birth defects, women of child-bearing age should consume 400 Xg of folic acid per day (but not more than 1000 Xg/day) from fortified foods and/or dietary supplements in addition to folates obtained from a varied diet. " < Ascorbic acid intakes of 80-200mg daily (8-20 times the amounts needed to prevent scurvy) may be necessary to enhance certain physiological functions and minimize specific disease risks. " ... 

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