More long-term safety data needed for folic acid fortification, says scientist

Their findings are backed by another study in the same journal that reveals the failure of public health advice to have a preventative effect on neural tube defects.

The authors voice support for the fortification camp, which has for several years called on governments to introduce folic acid fortification of flour or a staple food to improve uptake of this nutrient in women.

But scientists writing in Nature Review Genetics​ (vol 6, issue 3, pp235-40) this month raise new questions about the long-term safety of such an approach.

In the UK study, researchers reviewed prevalence of neural tube defects in 16 European countries between 1980 and 200 and found no substantial decline in neural tube defect rates in Continental Europe in the past decade. Although levels in the United Kingdom and Ireland fell by 32 per cent (a continuation of a long-standing decline), they remain higher than levels in Continental Europe.

The figures suggest that policies recommending supplementation of folic acid before conception and during early pregnancy are not effective enough, say the authors.

The alternative is fortification, already introduced by the US, Canada and Chile. European governments have however been reluctant to follow such an initiative. After a review of the evidence, the UK said that a higher intake of folic acid across the whole population could mask deficiency of the B12 vitamin in the elderly.

However Mark Lucock of the University of Newcastle in Ourimbah, Australia, and Zoe Yates of the University of Leeds, UK, write that long-term fortification could also impact our genetic make-up over time.

A small number of studies have found that the babies of women with a high folic acid intake are more likely to carry the gene form 677T MTHFR, which is involved in metabolizing the vitamin.

Such studies suggest that foetuses carrying this gene variant are more likely to survive to birth. But the 677T MTHFR variant has also been linked to an increased risk of certain diseases in adults, including heart disease, certain forms of cancer and pregnancy complications.

In those populations that are getting higher levels of folic acid, either through fortification or supplements, the number of people carrying this gene variant could be climbing, say the researchers, raising the risk of disease.

In a report on the paper in Nature​ this week, Lucock explains that some studies have found that the harmful effects of the gene are more common when people's diets are low in folic acid. The reasons for this are unclear, but if diets remain rich in the vitamin, this would compensate for any adverse impacts of 677T MTHFR.

However widespread fortification could create a future population that is artificially dependent on copious quantities of the vitamin - and one that would be more vulnerable to certain fatal diseases if that supply vanished.

Lucock believes that the health benefits of folic-acid fortification for pregnant women still outweigh the potential future risk, according to the report, but until the potential health risks of fortification are clearer, he suggests that governments could consider lowering their recommendation on how much folic acid should be added to food.

However human geneticist Larry Brody at the National Human Genome Research Institute in Bethesda, Maryland, told Nature​ that folic-acid fortification would change the genetics of the population so slowly that the effects would never be seen.

"It would probably take a couple of thousand years,"​ he told the journal.

Each year, more than 4500 pregnancies in the European Union are affected by neural tube defects.

Many women do not receive or respond to health promotion messages stressing the need to take supplements before conception, and a large proportion of pregnancies in most countries are unplanned, making supplements of little use.

"The potential for preventing neural tube defects in Europe by raising folate status is still far from being fulfilled, and it is unacceptable to continue to rely mainly on prenatal screening and termination to reduce the number of babies born with neural tube defects,"​ concludes the UK team in the 12 March issue of the BMJ (330, pp574-5).