Homocysteine concentrations and methionine loading in patients on antiepileptic drugs

Acta Neurol Scand. 2000 Apr;101(4):217-23. doi: 10.1034/j.1600-0404.2000.101004217x./.


Objectives: A few reports have shown elevated fasting total plasma homocysteine (tHcy) in patients taking antiepileptic drugs (AEDs). In this study we determined the influence of AEDs on plasma tHcy levels prior to and following methionine loading.

Material and methods: Thirty-four patients on different AEDs and 34 matched controls were recruited. Blood samples were drawn prior to and 6 h post-methionine loading (6h-PML).

Results: The patients on AEDs inducing the cytochrome P450 (carbamazepine, phenytoin, phenobarbital, primidone), had higher fasting and 6h-PML plasma tHcy concentrations than the controls (P = 0.01 and P<0.001). Patients on AED inhibiting the cytochrome P450 (valproate [VPA]), had lower 6h-PML p-tHcy concentrations than controls (P = 0.01).

Conclusions: Our data indicate that not only fasting but also 6h-PML tHcy levels should be determined in order to identify hyperhomocysteinemia among patients on AEDs. Inducer AEDs seem to have an opposite effect than the inhibitor VPA on plasma tHcy, erythrocyte folate and serum folate levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anticonvulsants / adverse effects
  • Anticonvulsants / pharmacology*
  • Carbamazepine / pharmacology
  • Case-Control Studies
  • Cytochrome P-450 Enzyme System / drug effects*
  • Epilepsy / drug therapy
  • Female
  • Folic Acid / blood
  • Homocysteine / blood*
  • Homocysteine / drug effects*
  • Humans
  • Hyperhomocysteinemia / blood
  • Hyperhomocysteinemia / chemically induced*
  • Hyperhomocysteinemia / enzymology
  • Male
  • Methionine*
  • Middle Aged
  • Phenobarbital / pharmacology
  • Phenytoin / pharmacology
  • Primidone / pharmacology
  • Treatment Outcome
  • Valproic Acid / pharmacology
  • Vitamin B 12 / blood


  • Anticonvulsants
  • Homocysteine
  • Primidone
  • Carbamazepine
  • Valproic Acid
  • Phenytoin
  • Cytochrome P-450 Enzyme System
  • Folic Acid
  • Methionine
  • Vitamin B 12
  • Phenobarbital