Folic acid fears for fetus unfounded: Study

By Stephen Daniells

- Last updated on GMT

Related tags Folic acid

Supplements containing folic acid, a key recommendation for women of child-bearing age, do not produce an accumulation of un-metabolized folic acid in the fetus, says a new study from Germany.

The findings, published in the American Journal of Clinical Nutrition​, support the safety of folic acid, with no accumulation of folic acid measured in 87 pregnant women, 29 cord blood samples, and 24 mother-infant pairs.

“Our findings in this non-fortified population imply that most of the folic acid in the region of 400 micrograms folic acid given to pregnant women was converted to active folates in most individuals,”​ wrote researchers led by Rima Obeid from the University Hospital of Saarland.

In an accompanying editorial by Arthur Beaudet and Robin Goin-Kochel from Baylor College of Medicine in Texas, the study was described as “relatively reassuring with regard to the possibility of harm through accumulation of un-metabolized folic acid”​.

B for baby benefits

An overwhelming body of evidence links folate deficiency in early pregnancy to increased risk of neural tube defects (NTDs) - 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.

Preliminary evidence indicates that the measure is having an effect with a reported 15 to 50 per cent reduction in NTD incidence. A total of 51 countries now have some degree of mandatory fortification of flour with folic acid.

However, similar measures in other countries have been opposed by concerns that the folate/folic acid may mask vitamin B12 deficiency, which leads to a form of neurological problems.

Concerns had also been raised for a potential build up of folic acid in the fetus, and the effects of this are unknown.

“The question of whether folic acid supplementation during pregnancy might cause the accumulation of un-metabolized vitamin in maternal or fetal circulation is a very important issue,”​ explained the researchers.

The new study was located in Germany – a population that does not have mandatory fortification with folic acid, and that relies on recommendations for folic acid supplementation to increase intake levels.

Study details

The German researchers investigated levels of total folate, folic acid, tetrahydrofolate (THF), 5-methyltetrahydrofolate (5-MTHF), formyl-THF, and 5,10-methenylTHF in the blood of 87 pregnant women, 29 umbilical cords, and 24 mother-infant pairs.

Results showed that “concentrations of folic acid were non-significantly higher in cord blood from supplemented women than in cord blood from non-supplemented women”​, while “proportions of folic acid to total folate in cord serum did not differ according to maternal supplement usage”​.

The researchers noted that, while folic acid is “not likely”​ to accumulate in the fetus, 5-MTHF and THF are likely to accumulate in the fetus.

“Our results show that concentrations of 5-MTHF and THF, but not of folic acid, were higher in cord than in maternal serum,” ​wrote the researchers. “Maternal folic acid supplement use did not explain the detection of un-metabolized folic acid in maternal blood or cord blood.”


In the editorial, Beaudet and Goin-Kochel said that the German study “provides reassuring information that suggests that unmetabolized folic acid does not accumulate substantially in the cord blood of newborns; this reduces concern regarding the possible toxicity of unmetabolized folic acid”​.

“The likelihood that increased intake of folic acid has harmful effects is low but perhaps not zero,”​ they added. “Most important, increased intake of folic acid definitely reduces the incidence of NTDs and therefore has a major, well-documented benefit.

“Thus, there should be no argument for decreasing intake of folic acid, but perhaps more research is needed regarding the small possibilities of harm or of additional benefits,”​ they concluded.

Source: AJCN
Volume 92, Pages 1416-1422, doi:10.3945/ajcn.2010.29361
“Concentrations of unmetabolized folic acid and primary folate forms in pregnant women at delivery and in umbilical cord blood”
Authors: R. Obeid, M. Kasoha, S.H. Kirsch, W. Munz, W.Herrmann

Editorial: AJCN
Volume 92, Pages 1287-1288; doi:10.3945/ajcn.110.004473
“Some, but not complete, reassurance on the safety of folic acid fortification”
Authors: A.L. Beaudet, R.P. Goin-Kochel

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