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

Background: All flour in the USA is fortified with folic acid at a level of 140 mu g/100 g which is estimated to supply an extra 100 mu g 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 mu g folic acid supplements daily for 14-weeks, healthy folate replete adults (n = 20) consumed folic acid fortified bread, at three different levels (400 mu g, 200 mu g, 100 mu g) 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 mu g or 100 mu g (current US regime) doses tested but was present at the highest level (400 mu g) tested. Conclusion: Our findings suggest that persons exposed to the current US fortification programme supplying an average of 100 mu g 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 mu g or less is unlikely to be problematic. Increasing the level however to 400 mu g on the other hand is likely to lead to unmetabolised folic acid appearance.