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Oxford Project to Investigate Memory and Ageing (OPTIMA)
Department of Physiology, Anatomy and Genetics
Parks Road
University of Oxford
Oxford OX1 3PT
United Kingdom
E-mail: david.smith{at}pharm.ox.ac.uk
Dear Sir:
The information presented by Berry et al is of considerable interest, but perhaps not very surprising in that it shows that 92% of the elderly with the highest blood folate concentrations are consuming supplements containing folic acid. I did point out in my editorial that high blood folate concentrations, particularly unmetabolized folic acid, are not only a consequence of fortification but also of supplement use (1). What is irrefutable is that blood concentrations of folate increased dramatically in the United States after mandatory fortification was introduced, with the concentration of serum folate increasing from a median of 12.5 nmol/L to a median of 32.2 nmol/L (2). Furthermore, the skewness toward higher levels apparent before fortification is just as marked as after fortification (2); this skewness might be due in part to the use of supplements (3).
Whereas Berry et al focus on the elderly, these changes also relate to young children. The data reported by Pfeiffer et al (2) show that the section of the US population with the highest blood folate concentrations after fortification was children aged 5 y, 43% of whom had serum folate concentrations >45.3 nmol/L. Ten percent of these children had concentrations >77.3 nmol/L. Using the formula provided by Quinlivan and Gregory (4), we can estimate the dietary folate intake in folic acid equivalents: 43% of children aged <5 y are consuming the equivalent of >780 µg folic acid/d, ie, double the Institute of Medicine's proposed tolerable upper limit (300–400 µg/d) for children of that age. What is of greater concern is that 10% are consuming the equivalent of >1320 µg folic acid/d, which is well above the tolerable upper limit of 1000 µg/d for adults. The next highest blood concentrations were found in children aged 6–11 y. It is plausible, as Berry et al suggest for the elderly, that such high concentrations are in part the result of supplement use in young children (5). However, it is perhaps more likely that the high concentrations in children are the consequence of 2 factors: the consumption of large amounts of bread and a diet rich in fortified ready-to-eat breakfast cereals. We simply do not know whether these high blood concentrations cause harm, but it must be of concern that such concentrations occur in children during a rapid stage of development. The study by Morris et al (6) highlights the potential importance of the correct balance between folate and vitamin B-12 in the elderly and we should consider whether a similar balance is important in young children, especially in parts of the world where many children have a low vitamin B-12 status.
Berry et al believe that a delay in implementing folic acid fortification in other countries would be detrimental to public health. This is likely to be the case in relation to neural tube defects, but should millions of people have to eat food fortified with folic acid without choice? The point that I was trying to make in my editorial is that fortification might potentially harm more people than it would benefit. The benefit of fortification in relation to neural tube defects would be negated if only 1 in 100 000 subjects eating folic acid–fortified food in the United Kingdom and North America experienced a serious adverse effect. Mandatory fortification exposes the entire population to extra folic acid, including those that might be susceptible to harm from such. This situation is quite different from the individual choice of taking supplements and from targeted interventions that might in the future be indicated for some sectors of the population (7) in addition to women planning to become pregnant. What we can all agree on is that more research is needed concerning the benefit and harm of folic acid. In my opinion, it is the responsibility of health authorities to conduct such research before folic acid fortification is introduced in additional countries on the basis of the evidence that is currently available.
ACKNOWLEDGMENTS
The author had no conflict of interest to report.
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