DRUG AND ENVIRONMENTAL-FACTORS ASSOCIATED WITH ADVERSE PREGNANCY OUTCOMES PART III - FOLIC-ACID - PHARMACOLOGY, THERAPEUTIC RECOMMENDATIONS, AND ECONOMICS

OBJECTIVE: To review folic acid's mechanism of action, adverse effects , therapeutic recommendations, compliance, and cast. DATA SOURCES: A M EDLINE search was conducted through December 1997. Additional sources were obtained from Current Contents and citations from the references obtained. Search terms included folate, folic acid, neural tube defect , homocysteine, and methylenetetrahydrofolate reductase. STUDY SELECTI ON: Animal and human studies examining the effects of folate were revi ewed. DATA EXTRACTION: Data collected included mechanism of action, sa fety issues, dosing recommendations, compliance with recommendations, and economics. DATA SYNTHESIS: Folic acid decreases neural tube defect risk through an effect on methionine-homocysteine metabolism. In addi tion, increased folate intake may reduce cardiovascular morbidity and mortality. Since toxicity is minimal, everyone can potentially benefit from increased folate consumption. To help achieve this, the Food and Drug Administration has mandated that cereal grain be fortified with 140 mu g of folic acid per 100 g of grain, which will add approximatel y 0.1 mg of folate to the average diet. Studies recommend supplementin g with 0.2 mg to promote optimal homocysteine concentrations and for p reventing neural tube defects. CONCLUSIONS: Despite fortification, mos t women will still receive less folate than the 0.4 mg/d recommended b y the Public Health Service. Ail population groups would benefit from increased folate intake. Current studies indicate 200 mu g/d may be th e minimum effective amount of fortification needed for normalizing hom ocysteine concentrations and preventing a significant number of neural tube defects; thus, a higher level of food fortification may be warra nted.