Long term effects of folic acid fortification questioned

By Stephen Daniells

- Last updated on GMT

Related tags: Folic acid

Since the introduction of mandatory fortification of grain products in the US, circulating levels of folic acid have doubled, says a new study.

The average blood concentration of folic acid has increased from 0.25 to 0.50 nanomoles per litre among non-supplement users, according to a study of about 3,000 Americans published in the American Journal of Clinical Nutrition​.

Amongst people who used supplements, folic acid concentrations rose from 0.54 to 0.68 nanomoles per litre, report the researchers from the Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Boston University School of Medicine.

“The biochemical and physiologic consequences of this are unknown, but these findings highlight the need to understand the effects of chronic exposure to circulating folic acid,”​ wrote lead author Renee Kalmbach.

The study’s findings are important around the world as other countries are considering introducing folic acid fortification.

Folate is found in foods such as green leafy vegetables, chick peas and lentils, and an overwhelming body of evidence has linked folate deficiency in early pregnancy to increased risk of neural tube defects (NTD) - most commonly spina bifida and anencephaly - in infants.

This connection led to the 1998 introduction of public health measures in the US and Canada, where all grain products are fortified with folic acid - the synthetic, bioavailable form of folate.

While preliminary evidence indicates that the measure is having an effect with a reported 15 to 50 per cent reduction in NTD incidence, parallel measures in European countries, including the UK and Ireland, are still on the table.

Study details

The researchers analysed blood samples of participants from the cross-sectional Framingham Offspring Cohort before and after the introduction of folic acid fortification to measure circulating levels of folic acid and its metabolite 5-methyltetrahydrofolate (5-MeTHF).

The predominant form found in the blood should be 5-MeTHF, but excessive folic acid intake may overload the body's capacity to metabolise folic acid to 5-MeTHF, which would lead to a build-up of folic acid.

Kalmbach and co-workers found that blood levels of folic acids had indeed increased. Moreover, the prevalence of high circulating folic acid had increased by almost 10 per cent, from 9.4 to 19.1 per cent, among non-supplement users. Among users of supplements, the prevalence of high circulating folic acid increased from 15.9 to 24.3 per cent, said the researchers.

With measures to introduce mandatory fortification of grain products in other countries, the need to better understand the effects of these chronic levels of circulating folic acid is important, concluded the researchers.

Source: American Journal of Clinical Nutrition​September 2008, Volume 88, Number 3, Pages 763-768“Circulating folic acid in plasma: relation to folic acid fortification”​Authors: R.D. Kalmbach, S.F. Choumenkovitch, A.M. Troen, R. D'Agostino, P.F. Jacques, J. Selhub

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