Case for folic acid to be added to flour is 'overwhelming' argues review

BBC News today reports: "'overwhelming' evidence for adding folic acid to flour".

Folic acid is a type of vitamin B that is essential to good health. It helps the body produce red blood cells, and is crucial during the first weeks of pregnancy to help the baby's brain and spinal cord develop. This is why all women trying for a baby or in the first 12 weeks of pregnancy are advised to take a folic acid supplement (400mcg daily) to help prevent birth defects like spina bifida.

But a new review says this isn't enough, and presents evidence that less than a third of all women in England take folic acid before pregnancy, despite clear public health campaigns.

Given that many pregnancies are unplanned, women may not start taking folic acid until they realise they are pregnant when it may already be too late to give benefit.

81 countries worldwide currently fortify flour, although no EU countries do. This is due to concerns that too much folic acid may be problematic for people with a B12 deficiency.

The current EU upper limit for folic acid is set at 1mg per day, which prevents flour fortification as this would cause some people to exceed the daily limit. The authors argue that the evidence on the harms of exceeding this limit is flawed.

The review itself should largely be considered as the opinions of the authors. Many experts have reacted and their views are quite mixed – some overwhelmingly in support of fortification while others have reservations. It remains to be seen whether EU or UK policy on this will change in the future.

Where did the story come from?

The study was carried out by three researchers from Queen Mary University of London. No sources of funding are reported and the authors declare no conflict of interest. The study was published in the peer-reviewed medical journal Public Health Reviews, and is freely available to access online.

The UK media's reporting of the study was accurate and most news sources provided opinions from independent experts who offered a range of views.

What kind of research was this?

This is a narrative review where the authors present the case for fortification of flour with folic acid to prevent defects of the developing brain and spinal cord (neural tube defects).

The authors say the two types of neural tube defects, spina bifida and anencephaly, are the most common serious birth defects worldwide, affecting 1-2 in 1,000 pregnancies.

Spina bifida is the more common, where the bottom of the spinal cord and surrounding vertebrae don't form properly leading to a gap in the spine. This can cause problems with walking, and bladder and bowel control. The child may also have learning disabilities.

The rarer but more serious condition of anencephaly is where the neural tube hasn't closed at the top, so the brain and skull haven't formed correctly. Most babies with anencephaly are stillborn or will die in infancy.

However, adequate folic acid intake can completely prevent these conditions. It can be given in vitamin supplements and – as the authors suggest – added to staple foods like flour.

The main drawback of this review is that the authors' methods aren't provided. They don't describe how they identified, appraised or selected the literature they discuss in the article. As such it cannot be described to be a systematic review that has identified all relevant literature on the topic. Some evidence in favour or against may have been missed.

What evidence does the review present ?

The authors first discuss the preventative effect of folic acid and evidence for folic acid supplement use during pregnancy, before moving onto the possibility of mandatory fortification.

They describe how a randomised controlled trial from 1991 first indicated that taking 4mg of folic acid during pregnancy (10 times the current recommended dose) could prevent about 80% of neural tube defects. On the basis of this trial it was concluded that these defects are due to a vitamin deficiency that needs correcting before pregnancy.

However, they say that despite campaigns, a study of nearly 500,000 women in England showed that less than a third took folic acid supplements before pregnancy.

This varied by age, the highest use was in women aged 35-39, 38% of whom took folic acid before pregnancy, compared with only 13% of those aged 20-24 and 7% under 20. There was also marked ethnic variation, with 35% of white women taking folic acid compared with 20% of South Asian and 18% of Afro-Caribbean women.

Just under two-thirds of all women took supplements in early pregnancy. But the researchers say this is already too late and the current strategy of encouraging women to take folic acid before pregnancy is inadequate and in particular is putting younger women and minority groups at a disadvantage.

What is the case for mandatory folic acid fortification?

As of October 2017, 81 countries had introduced mandatory fortification of flour. This includes the US, Canada and Australia, but so far no countries in the EU. The authors suggest this is because some expert committees undervalue the benefits of folic acid. The European Commission Scientific Committee on Food reportedly consider low folate as a "risk factor" rather than an "important cause" of neural tube defects.

There is also a widely held view that public health involves encouraging personal choice – such as through taking supplements – rather than making choices for everyone.

The authors say that fortification would not give full protection but would be "a population safety net" for women who haven't taken supplements before pregnancy. They give examples of legislation – such as smoking bans and car seatbelts – to reduce harm even if they impinge on personal freedom.

They mention how flour is already fortified with iron, calcium and other B vitamins like thiamine and niacin. They also say how folic acid would have wider benefits than just preventing neural tube defects, including reducing anaemia due to folate deficiency in older adults.

What do they say about possible harms?

The authors say: "with such evidence, the imperative for government to implement fortification is overwhelming." The only factor that could weigh against this is evidence of harms. In this regard they report that the Food and Nutrition Board at the Institute of Medicine (IOM) of the National Academies in the US found no evidence of harm from folic acid or folate.

However, IOM did think folic acid supplementation may be problematic for people with vitamin B12 deficiency, which is a condition where lack of vitamin B12 causes the body to produce abnormally large red blood cells that can't function properly.

As folic acid is similar to vitamin B12, this could partially compensate for the lack of vitamin B12. One concern is that this will lead to a delay in diagnosis which could allow neurological symptoms, such as neuropathy (nerve damage which can result in symptoms such as nerve pain and reduced motor function) to develop.

However, the review argues that with adequate diagnostics this shouldn't be a concern.

The IOM found neurological progression in B12 deficiency with folate intake above 5mg/day. However, it further lowered the "tolerable upper intake" to 1mg per day. The authors say this is impeding a fortification programme as people already consuming high levels of folate through their diet will inevitably go above this. They say that setting this upper limit on the grounds of risk in B12 deficiency was flawed in light of the fact that diagnostic procedures for vitamin B12 deficiency have improved since the IOM recommendations were written (1998). They say that "withholding a benefit is itself a harm."

What did the researchers conclude?

The authors conclude: "The correct public health policy message is simple: flour should be fortified with folic acid so that, on average, folic acid intake is increased by at least 0.2mg a day and preferably by about 0.4mg.

"The use of an upper intake level for folate should be abandoned. We suggest that there are grounds for the US IOM to reconsider its opinion on this issue in the light of the evidence and reasons given in this paper."

Conclusion

The authors present a compelling case for folic acid fortification in flour to prevent neural tube defects.

The main drawback of this review is the lack of information on the research methods. It cannot therefore be considered to be a systematic review as it's not possible to say that all evidence both for and against folic acid supplementation has been comprehensively reviewed. As such this review has to be considered largely the interpretation and opinion of the authors.

Nevertheless, the fact that a majority of women, particularly in more vulnerable groups, do not take folic acid supplements before pregnancy cannot be denied.

Expert reaction to the review was mixed, with many supporting mandatory fortification, but others cautioning against it.

Dr Ian Johnson, Nutrition researcher and Emeritus Fellow, Quadram Institute Bioscience, said: "The new paper … is a timely reminder that the protective effect of dietary supplementation with folates against neural tube defects has been conclusively proven, and that much more could be achieved with mandatory fortification of cereal foods."

Meanwhile Professor David Smith, Professor Emeritus of Pharmacology and Founding Director of the MRC Anatomical Neuropharmacology Unit, University of Oxford, countered:

"I cannot say whether the Institute of Medicine might have made an error in defining the safe upper limit of folic acid intake as 1mg per day from the evidence at their disposal in 1998. The issue clearly needs to be re-examined in the light of current evidence. However, the IOM view is certainly not the only reason why many scientists today are concerned about mandatory folic acid fortification."

He goes on to present two key facts, firstly that folic acid is a synthetic chemical, different from natural food folate, and is metabolised slowly particularly in people with certain genetic defects.

Secondly, to prevent a single neural tube defect, between 580,000 and 844,000 of the UK population would be exposed to extra folic. He says: "Can we be sure that in this large proportion of the population no-one would suffer harm from the folic acid? The answer must be 'No, we cannot be sure'."

It's not possible to say at this stage what future decision the EU authorities will make on this subject.

For now current government recommendations stand: People need 200mcg of folic acid a day, which can be obtained through many foods like green vegetables and fortified cereals. Women are advised to take a daily 400mcg supplement when planning to have a baby and for the first 12 weeks of pregnancy.

Read more about Vitamins, supplements and nutrition in pregnancy.