Study: EU should consider mandatory folic acid fortification

26 Nov 2015

A study published in the British Medical Journal concludes that EU authorities should take note of work done on the relationship between folic acid consumption and the reduction of neural tube defects and look at compulsory fortification.

Study: EU should consider mandatory folic acid fortification

In 1991 the UK Medical Research Council published the finding that women who took folic acid before conception could reduce their babies’ risk of a neural tube defect by as much as 72%, notes an editorial in the BMJ (British Medical Journal). The US Public Health Service met and quickly issued a recommendation that all women of childbearing age capable of becoming pregnant should take 400 µg folic acid daily. Some of us who attended the meeting, the authors continue,had doubts that women would take folic acid as instructed. Half of pregnancies are unplanned, and these women could be less motivated to take folic acid. In fact, many folate related neural tube defects were not prevented despite this recommendation and voluntary fortification in the United States. This led the United States to institute mandatory fortification of all enriched cereal grains (cereal, bread, rice, pasta) in 1998. Almost 80 countries have now instituted similar programs, and countries that fortify have experienced dramatic falls in rates of neural tube defects. Given that the recommendation that women take supplements had a modest effect in the United States, it is not surprising that Khoshnood and colleagues have shown that the European Union’s current strategy of recommending supplements, although useful, is failing to prevent many folate related neural tube defects.

How should the EU authorities react to these findings? A great deal has been written about the benefits and risks of food fortification—far too much to review here, the authors say. In brief, it is very clear that fortification will prevent approximately half of all neural tube defects. From both human and financial perspectives, this is a great benefit. Fortification has helped other segments of the population by greatly reducing rates of folate deficiency. One major problem is the masking of the diagnosis of vitamin B12 deficiency when high doses (1 mg/day) are consumed.

Other benefits and risks are less clear. Population studies suggest that folic acid in the doses present in fortified food does not prevent other birth defects.7 Attempts to reduce recurrence of cardiovascular disease with folic acid and related B vitamins have produced largely negative results but have shown no adverse effect on cardiovascular disease either. These trials of supplements have provided an opportunity to examine other outcomes potentially associated with folic acid intake, notably cancer.

The literature on cancer is inconsistent. The EU could use some standard criteria to determine whether a causal association is present between folic acid and cancer. The criterion of consistent positive findings is not met. The strength of association between folic acid and cancer is weak, if present at all. Biological plausibility could be argued either way. Folic acid may promote the growth of existing cancers, yet folate also provides carbon atoms for repair of DNA, potentially averting carcinogenesis. An important, unanswered question is, “What does folic acid do to pre-malignant lesions?” Again, the limited data are inconsistent. There is no coherence across various types of study, so another criterion is not met. Thus, the evidence to date does not demonstrate a causal link between fortification and cancer.

Because cancer is very common, even a small increase in relative risk, if real, could cause a serious increase in the number of cancers. Does evidence exist for an increase in cancer rates since fortification began? Although one cannot draw definitive conclusions from ecological data, rates of all cancer, colorectal cancer, and prostate cancer have decreased significantly since folate fortification began in the United States.

The safety of folic acid has been the subject of intensive investigation. Asthma, cognition, autism, twinning, telomere shortening, and blocking of the effects of anti-folate drugs are among the outcomes studied. An expert panel convened by the National Toxicology Program and Office of Dietary Supplements at the US National Institutes of Health has recently identified four priority areas for further research into the potential risks of high dose folic acid: cancer, hypersensitivity related problems, thyroid/diabetes, and cognition. The concern is exposure to high doses of more than 1 mg/day.

One of the challenges to implementing compulsory fortification is choosing a level that will prevent neural tube defects without exposing the population to excessive doses, the authors say. Current levels of fortification in the United States (140 µg folic acid/100 g enriched cereal grain) provide on average 163 µg/day to women of childbearing age. Fortunately, this level is highly successful in preventing folate related neural tube defects. Thus, providing women at risk with enough folic acid without exposing others to excessive amounts should be possible. Doing so will require careful consideration of the effect of other fortified foods and supplements to avoid excess exposure.

Khoshnood and colleagues have shown that the EU’s current strategy is failing to prevent many neural tube defects. Mandatory fortification has been shown to work in many countries, including the United States. No important adverse effects have been identified to date, probably because a modest level of fortification has proved very effective in preventing these devastating birth defects. Khoshnood and colleagues’ findings should prompt the relevant authorities in the EU to take a further look at the compulsory fortification option.