Folate and Neural Tube Defects

Much attention has focused over the past 15 years on a number of diseases for which the risks are inversely related to folate status even within the range of serum folate levels previously considered 'normal.' Foremost among these is NTD, a malformation in the developing embryo that is related to a failure of the neural tube to close properly during the fourth week of embryonic life. Incomplete closure of the spinal cord results in spina bifida, while incomplete closure of the cranium results in anencephaly. The risk of NTD was found to be 10-fold higher (6 affected pregnancies per 1000) in people with poor folate status (i.e., less than 150 mg red cell folate per litre) than in those with good folate status (400 mgl-1). International agencies have published folic acid recommendations for the prevention of NTD. To prevent recurrence, 5 mg of folic acid daily in tablet form is recommended, while 400 mg daily is recommended for the prevention of occurrence, to be commenced prior to conception and continued until the 12th week of pregnancy. Given the high proportion of unplanned pregnancies, the latter recommendations are applicable to all fertile women. This amount, however, could not be introduced through fortification because high intakes of folic acid by people consuming fortified flour products would risk preventing the diagnosis of pernicious anemia in the general population and of vitamin B12 deficiency in the elderly.

The introduction of 140 mg of folic acid per 100 g of flour in the USA, calculated to increase individual consumption of folic acid by 100 mgday-1, has reduced the incidence of abnormally low plasma folate from 21% to less than 2%, the incidence of mild hyperhomocysteinemia from 21% to 10%, and, most importantly, the incidence of NTD by about 20% over the first years of universal fortification. Because 30% of the population takes vitamin supplements and presumably would not be expected to derive significant benefit from fortification, the actual effect may be closer to a 30% decrease due to fortification. Recent calculations suggest that, for a variety of reasons, the overall fortification amount was about twice the mandatory amount.

On balance, the introduction of food fortification with folate is regarded as beneficial not only in preventing NTD but also in reducing the incidences of hyperhomocysteinemia (mentioned earlier), color-ectal cancer, and a number of neurological and neu-ropsychiatric diseases in which folate is postulated to play a protective role.

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