Researcher reflects on fortification progress 25 years after landmark study

Not fortifying with folic acid is 'like having the polio vaccine and refusing to use it'

11 May 2016

Twenty-five years ago The Lancet published results of a randomized controlled trial that has contributed to 80 countries requiring folic acid to be added to at least one cereal grain through fortification. Those countries do not include any of the 28 countries in the European Union even though their modern flour milling industry could easily manage the technical implementation, and foods made with wheat flour are commonly consumed.

Sir Nicholas WaldNot fortifying with folic acid, despite repeated evidence that it is a safe and cost-effective public health strategy, is like having the polio vaccine and refusing to use it, Nicholas Wald has written. Wald, pictured at right, is Professor of Environmental and Preventive Medicine at The Wolfson Institute of Preventive Medicine, Queen Mary University of London.

Among his many other professional accomplishments, Wald was the lead author of the study which provided unquestionable evidence that folic acid would prevent most neural tube birth defects (NTDs) such as spina bifida. The study was funded by the British Medical Research Council. Wald is a Fellow of the Royal Society of the United Kingdom (UK) and Commonwealth which recognizes excellence in science. In 2008 he was knighted during the Queen’s Birthday Honors.

Yet the country that funds his research and recognizes his accomplishments is among those that continually resists fortifying flour with folic acid to prevent NTDs.

After results of Wald’s randomized controlled trial were published, the UK government “quite quickly recommended women to take folic acid supplements prior to pregnancy,” Wald recalled. “What they didn’t see was that many women would get pregnant without either knowing about folic acid or not taking supplements because they weren’t really planning the pregnancy.”

The recommendation to take folic acid supplements, if followed, would have increased blood folate levels. Yet blood samples taken between 2008 and 2012 showed that 85% of women aged 16-49 years in the UK did not have blood folate levels high enough to minimize the risk of a pregnancy being affected by an NTD. This is according to a National Diet and Nutrition Survey-Rolling Programme and noted by the UK Scientific Advisory Committee on Nutrition. Another paper published in 2013 estimated that 4,500 NTDs occur in the European Union annually; 72% of the affected pregnancies end in terminations.

Fortification opponents argue that the whole population should not have extra folic acid when only women need it to prevent NTDs. “Frankly, I think that’s a frightful notion,” Wald said. “Simply because women carry the baby doesn’t mean they’re the only ones who benefit. What about the fathers, the grandparents, the schools? Everyone benefits.”

'Historical Hangover'

Other opponents are concerned that fortifying with folic acid will hinder diagnosis and treatment of pernicious anemia. Wald said this is a “historical hangover.” In the 1940s and 1950s, patients with pernicious anemia were given large doses of folic acid which resolved the anemia but did not treat the related neurological damage. Scientists had not yet discovered that the pernicious anemia was caused by an immune disorder that destroys cells required for vitamin B12 absorption. Left untreated, the resulting vitamin B12 deficiency can lead to serious neurological problems.

Modern laboratory tests make it possible to accurately diagnosis pernicious anemia so that the related vitamin B12 deficiency can be treated. In New Zealand a study published in 2012 found that masking of the anemia of vitamin B12 deficiency is “negligible in current medical practice.”

A link between folic acid and cancer has also been suggested, but a meta-analysis of 50,000 individuals showed that was not the case. “A suggested finding needs to be investigated in a well-designed study that is independent of the work which raised the hypothesis - before we judge that the suggestion is true,” Wald advised.

It was that conviction that caused Wald to conduct the randomized controlled trial related to folic acid and NTDs. In the 1960s and 1970s some studies suggested that folic acid would prevent NTDs. The research was unclear about whether this was a genuine preventive effect, and if so, whether it was from folic acid alone or from other vitamins.

Skeptical at First

“I was skeptical that a vitamin deficiency could prevent these birth defects, but I couldn’t say it was groundless either,” Wald recalled. “If there’s an uncertainty, you need to do more research and resolve the uncertainty.”

Wald’s randomized controlled trial clearly showed that among women who had a previous pregnancy affected by a NTD, folic acid alone would reduce the risk of a second NTD-affected pregnancy by 70 to 80%. Another randomized controlled trial based in Hungary and published in 1992 also found a protective effect of folic acid in first-time pregnancies.

In the British study, the link between folic acid and NTDs was so clear that the trial had to be stopped early. It would have been unethical to continue giving a placebo with no folic acid to women so their pregnancies could be compared with those who received folic acid.

Now the European attitude seems to ignore this ethical consideration in its failure to add folic acid to flour that the majority of the population consumes.

Governments do not want legislation for things that individuals can take action to correct themselves, Wald said, even if in practice individuals do not take that action. Also, no country wants to stand apart from other countries in the European Union by being the only one with a mandate to fortify flour with folic acid, even if this is in the public interest.

In Wald’s opinion, these arguments are contrary to the nature of public health. “Effective public health is largely behind the scenes. It is building health and safety into the fabric of society, like taking lead out of petrol,” Wald said. Not requiring folic acid to be added to flour, he said, is evidence that “Europe fails to grasp the nature of public health.”