To the Editor: The editorial on mandatory fortification of flour with folic acid by Maberly and Stanley is subtitled: “The scientific benefit is clear, but translating this into practice requires advocacy”.1

The only benefit that is scientifically clear is the reduction in the incidence of neural tube defects. All the other “benefits” listed by the authors are observational and have occurred in a setting where myriad environmental changes have occurred concurrent with folic acid fortification. To imply that the reduction in the rate of heart attacks and stroke is the result of folic acid fortification is, at best, anecdotal, because it is not supported by any randomised controlled studies, and is an extrapolation from the relationship between reduced homocysteine levels and the incidence of stroke and heart disease.

The authors also did not mention the increased incidence of multiple pregnancies that has been observed with folate supplementation (relative risk, 1.02; 95% CI, 0.97–1.07).2 While this represents only a slight increase in the risks associated with the birth process, it should not be ignored when considering perceived risks. It is also possible that in a planned pregnancy where the mother is prescribed folic acid before conception, the additional folate intake from fortified flour may further increase the risk of multiple pregnancy.

It seems to me that the editorial was in fact an item of advocacy rather than a dispassionate scientific assessment of the arguments for and against mandatory folic acid fortification. At the very least, if mandatory folic acid fortification is implemented, prospective mothers will have to be made aware of the increased risk of multiple pregnancy and the as yet unknown risk of combining the fortified diet with medically prescribed folic acid.

In reply: Ekert suggests that in our article advocating for mandatory fortification with folate to reduce neural tube defects,1 we omitted to mention the “increased risk of multiple pregnancies”. He then misquotes the Lumley meta-analysis “(relative risk, 1.02; 95% CI, 0.97–1.07)” — the real relative risk was 1.40 (95% CI, 0.93–2.11). This Cochrane systematic review shows that folate supplementation does not carry a statistically significant risk for multiple births, but confirms the dramatic reduction in neural tube defects.2 Another study, which did suggest an increased risk, did not control for the known increased risk of multiple births following infertility treatments, which could explain the increase observed.3

Ekert suggests that we inform women about this unsubstantiated risk and “the as yet unknown risk” which mandatory fortification might add to “medically prescribed folic acid”. Folic acid is found in leafy green vegetables and in many fruits, nuts and other components of a healthy diet. Tablets are available over the counter. What advice would he give to women about these “risks”? Our evidence is that we are not reaching many women in our society by education and voluntary fortification, and that countries that have fortified their flour have achieved much better reductions in these major defects than we have in Australia. Hence our advocacy.

We acknowledge that the evidence for stroke and heart disease reduction is not as solid as that for neural tube defects. However, there is an increasing literature on the protective effects of folate on cardiovascular risk and possible mechanisms.4-8

Hence, with consideration of the proven benefits and the unsubstantiated risks, we will continue to advocate for the mandatory fortification of flour with folate.