Abstract
SummaryThe link between folate deficiency and congenital spina bifida defects was first suggested in the 1960s. Although the prevention of these defects by preconception folic acid supplementation was confirmed in a large multi-centre controlled trial in 1991, its subsequent implementation as health education advice has made very little difference. North America’s policy of folic acid fortification of flour and bread has had a beneficial impact. No European country has implemented fortification due to concern over possible adverse effects on older subjects, but a recent review shows these to be largely hypothetical and far outweighed by beneficial effects. Recent research by Menezo et al. has, however, shown that folic acid is ineffective for some women with severe fertility problems including recurrent miscarriage and failed in vitro fertilisation. There is a genetically determined bottleneck (677TT) in their folate metabolism that can be successfully overridden by going straight to the next step in the metabolic pathway and taking 5-methylytetrahydrofolate, as a preconception supplement. Menezo suggests that all women with fertility problems should be tested for 677TT. If fortification of flour and bread is to be implemented in the UK, there should be monitoring for possible adverse effects including the incidence of colorectal cancers and cognitive decline. In conclusion, whilst there are concerns that fortification could have a detrimental effect on these conditions, there is sound evidence that it would have much greater beneficial effects.
Highlights
The folic acid story began in 1964 when Bryan Hibbard was a young consultant obstetrician in Liverpool researching the causes of placental abruption. He found a link with folate deficiency and noted a higher incidence of congenital malformations in folate-deficient subjects (Figure 1).[1]
Leck[2] and Smithells et al.[3] suggested that folate deficiency had a causal link with congenital neural tube defect malformations
Subsequent research indicated that preconception folic acid significantly reduces the risk of neural tube defect malformations.[4,5]
Summary
The folic acid story began in 1964 when Bryan Hibbard was a young consultant obstetrician in Liverpool researching the causes of placental abruption. He found a link with folate deficiency and noted a higher incidence of congenital malformations in folate (vitamin B9)-deficient subjects (Figure 1).[1]. Leck[2] and Smithells et al.[3] suggested that folate deficiency had a causal link with congenital neural tube defect (spina bifida) malformations. They found that the commonest is spina bifida with meningocoele. This paper reviews: the limited success of preconception folic acid as a public health strategy[6,7] despite the success of controlled trials of folic acid;[4,5] the case for folic acid fortification of bread and flour; and the results of recent research that suggest there are limitations to recommending folic acid in some clinical circumstances
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