Folic acid fortification and public health: report on threshold doses above which unmetabolised folic acid appear in serum

Abstract

Background: All flour in the USA is fortified with folic acid at a level of 140 microg/100 g which is estimated to supply an extra 100 microg daily to the average diet. Some researchers have advocated that this be increased to double and even four times this amount. Based on previous research these higher levels are likely to lead to the appearance of unmetabolised vitamin in the circulation, which may have safety implications for sub-groups of the population. The UK and the Republic of Ireland will likely introduce mandatory fortification also in the next year or so. The aim of this study was to capture the short-term effect of folic acid fortification on unmetabolised folic acid in serum after chronic consumption of folic acid.

Methods: After pre-saturation with 400 microg folic acid supplements daily for 14-weeks, healthy folate replete adults (n = 20) consumed folic acid fortified bread, at three different levels (400 microg, 200 microg, 100 microg) over a period of one week each. The dose was administered in two-equal sized slices consumed at 09.00 hrs and 13.00 hrs. Serum samples for total folate and folic acid were collected at baseline, after 14-weeks of supplementation, and pre and post (at 1, 2, 3 and 4 hours) each dose tested.

Results: Unmetabolised folic acid was detected after the 14-week supplementation period. Folic acid was not detected in either the 200 microg or 100 microg (current US regime) doses tested but was present at the highest level (400 microg) tested.

Conclusion: Our findings suggest that persons exposed to the current US fortification programme supplying an average of 100 microg per day or less are unlikely to have unmetabolised folic acid in serum. It also seems that daily consumption of the higher level of 200 microg or less is unlikely to be problematic. Increasing the level however to 400 microg on the other hand is likely to lead to unmetabolised folic acid appearance.

Figure 1

This flow diagram illustrates diagrammatically the interventions and sampling points. Schematic summary of intervention phases and sample collection. * = Folate and Folic Acid blood sample. RCF = Red cell folate blood sample. § = Day 7, trial of bread regimes (200 μg, 100 μg, 50 μg).

Figure 2

Mean total serum folate (μg/L) and mean serum unmetabolised folic acid (μg/L) pre and post regime C bread (n = 19). This graph illustrates mean total serum folate (μg/L) and mean serum unmetabolised folic acid (μg/L) concentrations in a group of healthy adult subject (n = 19) exposed to a folic fortified bread for 1-week. Subject were pre-saturated with folic acid supplements for 14-weeks prior to the bread. The bread was fortified with 200 μg folic acid per slice, which was administered twice a day for seven days. The samples shown here were collected on the 7^th day of bread consumption pre-prandially and post-prandially.