Study may allay folic acid concerns

By Stephen Daniells

- Last updated on GMT

Related tags: Folic acid

Concerns over folic acid promoting embryos in the womb with
genotypes that increase the risk of disease in the offspring may be
unfounded, according to new research.

Folate and folic acid during pregnancy are well established to reduce the incidence of neural tube defects (NTD) - most commonly spina bifida and anencephaly - but Spanish researchers reported in 1998 that folic acid supplementation may increase the selection of embryos with a mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, which has been linked to an increase in the risk of the offspring developing disease. The new study, published in BJOG: An International Journal of Obstetrics and Gynaecology​, did not support these findings and offer support for the introduction of mandatory folic acid fortification. The connection between the B vitamin and NTDs 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. "Folic acid is known to be effective in reducing the incidence of [NTD], but concerns over possible effects on embryo selection continue to be cited as a potential reason for not fortifying the diet with folic acid and reservations about the use of folic acid supplements,"​ wrote lead author Paul Haggarty from Rowett Research Institute, Aberdeen. "We found no evidence to support these concerns."New data ​ Haggarty and co-workers conducted an observational prospective cohort study involving 1,234 women and 1,083 infants. The genotypes of mother and child were examined, with five specific genes targeted: MTHFR C677T and A1298C, MTR A2756G, MTRR A66G and TCN G776C. The mothers' supplement intake, and dietary intakes of folate and vitamin B12, along with the mothers' blood levels of these vitamins were measured at week 19 of the gestation period. No significant differences were found in any the five genotype frequencies between the mothers and their babies, with no link observed between the babies' genotypes and the mothers' use of supplements, dietary folate intake, or blood levels of folate. Perspective and ethics ​ The Spanish study reported a doubling of the frequency of the MTHFR 677 TT genotype. "These are very large effects and, if they arose as a result of folic acid use in pregnancy, would be of serious concern in relation to public health,"​ wrote Haggarty and co-workers. "The best study design to test this observation would be a randomised controlled trial of folic acid supplements in women intending to become pregnant. However, the evidence for a beneficial effect of folic acid on NTD is such that the inclusion of a placebo group would be unethical; therefore, an observational study such as that reported here is the only ethically acceptable design,"​ they said. A plausible biological mechanism does exist to explain the potential selection of genotypes that increase the risk of disease in the offspring, wrote the authors. However, their results did not prove that such an effect was occurring in reality. Haggarty also sits on the UK Scientific Advisory Committee on Nutrition that provides advice on folic acid fortification to the UK Food Standards Agency and Department of Health. Source: BJOG: An International Journal of Obstetrics and Gynaecology​ (Wiley-Blackwell) Volume 115, Pages 851-856, doi: 10.1111/j.1471-0528.2008.01737.x "Folic acid use in pregnancy and embryo selection"​ Authors: P. Haggarty, D.M. Campbell, S. Duthie, K. Andrews, G. Hoad, C. Piyathilake, I. Fraser, G. McNeill The Lancet​ 1998, Volume 352, pages 1120-1121, doi: 10.1016/S0140-6736(05)79761-0 "Genetic selection and folate intake during pregnancy"​ Authors: E. Munoz-Moran, J.L. Dieguez-Lucena, N. Fernandez-Arcas, S. Peran-Mesa, A. Reyes-Engel

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