They pointed out that its intake from food alone is insufficient in preventing neural tube defects in babies. In contrast, supplements provide exceedingly high amounts that could result in adverse effects such as pregnancy loss.
The team highlighted this urgency through their paper titled “Women Taking a Folic Acid Supplement in Countries with Mandatory Food Fortification Programs May Be Exceeding the Upper Tolerable Limit of Folic Acid: A Systematic Review”, published in the journal Nutrients.
“There is a risk that women may be exposed to unintended adverse health outcomes through excess folic acid intake. For this reason, it is imperative that preconception and pregnancy folate intake from all sources for women of childbearing age is more clearly understood,” said the researchers.
In October 2021, they devised a systematic review to assess the total intake of folate in women of childbearing age and pregnant in high-income countries with food fortification programmes. The review encompassed research published from 1998 to 2021, which was narrowed to 36 studies involving 52,580 women aged between 17 to 49.
The included studies were classified into two categories: women of childbearing age and pregnant. Their results were compiled into four areas of discussion: natural folate intake, food fortification intake, supplement intake and the rate of women exceeding the upper tolerable limit.
Understanding folate intake
Based on consensus, women of childbearing age need a minimum of 400mcg of folic acid daily in addition to normal dietary intake to reduce the risk of the foetus developing neural tube defects. The review found that women of that age are not getting enough folate – they are consuming only half the recommended dose on average, and it was derived from food. This insight was based on studies such as Pick (2005) and Hure (2008).
Hence, the US and Australian authorities mandated food fortification in 1998 and 2009, respectively. However, this move did not cap the number of foods being fortified, nor did it scrutinise populations that might be sensitive to large amounts of folic acid, such as children and older adults. No tailored intakes through supplementation were also suggested for women in the preconception and pregnancy stages.
Regarding folate measurement, the studies were shown to base their assumptions that folic acid has higher bioavailability than natural folates. However, emerging evidence conflicts with these studies. In addition, folate amounts are affected by factors such as cooking, intestinal pH and poor subject compliance. Hence, researchers must understand folate metabolism better to avoid underestimating the amount of natural folate and fortification.
Consequently, folate metabolism is affected by the upper tolerable limit of folic acid. There is also a difference between the metabolism of natural folates and folic acid. If mismanaged, there might be an accumulation of unmetabolised folic acid, as shown in studies conducted by Plumptre (2015) and others. This then begs the question of changing folate recommendations.
Moreover, high doses of folic acid could result in various issues like lower pregnancy rates, infertility and abnormal embryos, as highlighted in early studies such as Aarabi M. et al. (2015) and Lambrot, R. et al. (2013). The review has also confirmed that many women, preconceptionally and almost all at some stage of pregnancy, exceed the upper tolerable limit of 1,000 mcg daily. Due to the concerns raised by researchers on unmetabolised folic acid, the limit needs to be re-evaluated.
In conclusion, the researchers reiterated the risks faced by women on the opposite ends of the intake spectrum and urged regulators to review the current approaches for their safety.
“The results of this review warrant close attention from public health researchers and policymakers and may justify a review of the current approach to ensure folate sufficiency in the general population and avoidance of unmetabolised folic acid levels that may influence fertility and pregnancy outcomes,” the team said.
Source: Vitamins and Human Health: Systematic Reviews, Nutrients
“Women Taking a Folic Acid Supplement in Countries with Mandatory Food Fortification Programs May Be Exceeding the Upper Tolerable Limit of Folic Acid: A Systematic Review”
Authors: Carolyn Ledowsky et al.