Antiepileptic drugs as independent predictors of plasma total homocysteine levels

Epilepsy Res. 2001 Nov;47(1-2):27-35. doi: 10.1016/s0920-1211(01)00288-1.


Low folate levels have consistently been reported in patients with epilepsy on phenytoin (PHT), phenobarbital (PB) and primidone (PRD), while data on valproate (VPA) are conflicting. Furthermore, antiepileptic drugs (AEDs) may be associated with high levels of plasma total homocysteine (p-tHcy). Therefore, we have investigated the levels of p-tHcy, serum folate (S-FA) and erythrocyte folate (E-FA) in patients on PHT, PB and PRD (Group 1, n=21) and VPA (Group 2, n=24). Both groups had their own matched controls. Blood samples were drawn fasting and 6 h post methionine loading (6 h-PML). The Group 1 patients had fasting and 6 h-PML p-tHcy levels significantly higher than their controls (P=0.05 and <0.0001, respectively), and patients without dietary multivitamin supplementation (n=14), had lower fasting S-FA and E-FA levels than their controls (P=0.02 and 0.0003, respectively). The Group 2 patients had fasting and 6 h-PML levels of p-tHcy, S-FA and E-FA not different from their controls. In a multiple stepwise regression model comprising all subjects (n=90), the AEDs of Group 1 and the S-FA levels were independent predictors of p-tHcy levels. Thus, PHT, PB and PRD are associated with high p-tHcy and low folate levels, whereas VPA does not influence S-FA, E-FA and p-tHcy levels in adult patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Substitution / genetics
  • Anticonvulsants / therapeutic use*
  • Cholesterol
  • Cholesterol, HDL / blood
  • Confidence Intervals
  • Cysteine / genetics
  • Epilepsy / blood*
  • Epilepsy / drug therapy*
  • Epilepsy / genetics
  • Fasting / blood
  • Female
  • Folic Acid / blood
  • Homocysteine / blood*
  • Humans
  • Hyperhomocysteinemia / blood
  • Hyperhomocysteinemia / epidemiology
  • Male
  • Middle Aged
  • Mutation / physiology
  • Predictive Value of Tests
  • Prevalence
  • Statistics, Nonparametric
  • Threonine / genetics
  • Triglycerides / blood
  • Vitamin B 12 / blood


  • Anticonvulsants
  • Cholesterol, HDL
  • Triglycerides
  • Homocysteine
  • Threonine
  • Folic Acid
  • Cholesterol
  • Cysteine
  • Vitamin B 12