Will increasing folic acid in fortified grain products further reduce neural tube defects without causing harm?: consideration of the evidence.

To reduce neural tube defects (NTDs), the U.S. Food and Drug Administration (FDA) mandated that by January 1998 all enriched grain products should contain 140 microg of folic acid (FA)/100 g of flour. Groups concerned with optimal prevention of NTDs had argued that the level should be 350 microg/100 g. However, when it appeared that the debate might delay implementation of any fortification, these groups petitioned the FDA to implement fortification at the originally proposed level of 140 microg/100 g, anticipating that the FDA might consider increasing the level at a later time. Mandated FA fortification (FAF) has now been in place in the United States for 9 y. The impact of this important public health intervention on NTD rates, the possible benefit to other disease conditions, and potential harms have been evaluated. As background for a possible request that the FDA consider increasing FAF, evidence bearing on the question of whether an increase can further reduce NTD births without causing harm is reviewed here. The published data indicate that it is appropriate that the FDA conduct or commission a balanced analysis of the evidence by scientists who will act on that evidence to decide this important question.