Folic acid: when to supplement and by how much

Introduction

In 1931, Dr. Lucy Wills demonstrated that yeast extract was effective against the tropical macrocytic anemia seen in late pregnancy in India.1 In the subsequent decade, the compound responsible for this effect, folate, was isolated. Folate is a water-soluble B vitamin, found particularly in such foods as leafy green vegetables, citrus fruits, and legumes. Folic acid is the synthetic form of the vitamin, which is given as a supplement or added to fortified foods. The value of preconceptual dietary supplementation with folate in women of child bearing age in reducing major congenital malformations (MCMs) and neural tube defects (NTDs) has been demonstrated in a number of large studies. This has led to explicit guidelines from the American Academy of Neurology (ANN) and the European Registration of Congenital Anomalies and Twins (Eurocat) regarding such supplementation and fortification,2, 3 and has to led to folic acid fortification of food in many countries as a public health measure for the reduction of NTD occurrence rates.4

Abstract

INTRODUCTION

Folate is a water-soluble B vitamin, found particularly in such foods as leafy green vegetables and citrus fruits. Folic acid is the synthetic form of the vitamin. The value of pre-conceptual dietary supplementation with folic acid in women of child bearing age in reducing major congenital malformations (MCMs) and neural tube defects (NTDs) has been demonstrated in a number of large studies. However, the role and dosing of folic acid in women with epilepsy (WWE) who are taking anti-epileptic medication (AEDs) is less clear.

OBJECTIVE

To review the role of folate in the development of the neural tube and the evidence underlying the recommendations for folic acid supplementation in women of child bearing age and in WWE.

METHODS

We performed a formal literature search and from the results we reviewed the available studies and guidelines on the use of folic acid in the general population and in WWE.

CONCLUSION

Standard dose (0.4mg) of folic acid use should be encouraged in all women of childbearing potential, but the evidence to support the use of high-dose (ie, 5mg) folic acid in women who do not have a personal or family history of NTD/MCM occurrence is not strong. The evidence that folic acid supplementation will protect WWE from MCMs and NTDs is poor. However, given the potential interference in the metabolism of folate by some AEDs, high dose folic acid (5mg) should be prescribed in WWE but only in those without a personal history of malignancy.

Keywords

folic acid, women with epilepsy, supplementation, major congenital malformations