High dose folic acid supplementation in women with epilepsy: Are we sure it is safe?

Abstract

Most experts agree that folic acid supplementation is a key preconception intervention, particularly in women with epilepsy who take anti-epileptic drugs (AEDs). Primary prevention of neural tube defect through folic acid supplementation results in reduction of risk in an otherwise healthy population. The current folic acid supplementation recommendation is that all women of childbearing potential be supplemented with at least 0.4 mg of folic acid daily prior to conception and during pregnancy. It is recommended that all women with epilepsy and of childbearing potential be supplemented with folic acid daily prior to conception and during pregnancy. However, considering the potential significant drug-drug interactions between high doses of folic acid and some AEDs in patients with epilepsy and also with the emerging evidence from animal studies that high levels of folic acid throughout gestation may have adverse effects on fetal brain development, it is not suggested to advocate high dose folic acid supplementation in women with epilepsy until more information is available about its appropriate, safe and optimal dosing.

Verbal abilities in children of mothers with epilepsy

“… 2 The safety of high-dose folic acid supplement use in women with epilepsy and in the general population is still debated. 41 , 42 Folic acid dose recommendations cannot yet be specified for individual AEDs, although several AEDs interact with folic acid metabolism. 4 , 5 , 37 …”

Epilepsy in pregnancy

“…• The optimal dose for women with epilepsy is not clear for those taking antiepileptic drugs (some of which may be folate antagonists) 52 : 5 mg once daily is suggested in UK guidelines for at least the first trimester, but this could be continued throughout pregnancy without likelihood of harm. [44][45][46][47] US guidelines suggest at least 0.4 mg/day preconceptually and during pregnancy 48…”

High-dose folic acid supplementation results in significant accumulation of unmetabolized homocysteine, leading to severe oxidative stress in Caenorhabditis elegans

“…Moreover, folic acid supplementation reportedly has health-promoting effects as it prevents various diseases, such as type 2 diabetes and cardiovascular diseases (including stroke) [ 4 ]. However, excessive folic acid intake has been linked to the masking of cobalamin deficiency [ 5 ], and concern is now growing with regarding the adverse effects of long-term intake of high-dose synthetic folic acid [ [6] , [7] , [8] , [9] ]. In fact, high-dose folic acid supplementation has resulted in an increase in folic acid levels in the blood circulation [ 10 , 11 ].…”