title: Effects of common anti-epileptic drug monotherapy on serum levels of homocysteine, vitamin B12, folic acid and vitamin B6.
abstract: There is emerging evidence to support the unfavorable effects of some anti-epileptic drugs on the plasma homocysteine concentrations. Elevated homocysteine levels induced by anti-epileptic drug administration can theoretically increase not only the risk of vascular occlusive diseases, but also the risk of resistance to anti-epileptics and development of refractory epilepsy. To investigate the effect of common anti-epileptic drugs on the homocysteine metabolism, a total of 75 epileptic patients receiving phenytoin (n=16), carbamazepine (n=19), or valproic acid (n=22) and no anti-epileptic drug (n=18) were enrolled. Eleven age- and sex-matched healthy subjects served as the control group. Blood concentrations of homocysteine, folic acid, Vitamin B12 and pyridoxal 5'-phosphate (active circulating form of Vitamin B6) were measured. Compared to the control group, epileptic patients on anti-epileptic drug had higher blood levels of homocysteine. No difference in homocysteine concentrations was observed among epileptic patients in terms of the anti-epileptic drug used. Patients receiving phenytoin had significantly lower folic acid levels and those receiving carbamazepine had marginally lower pyridoxal 5'-phosphate levels in comparison with those using other anti-epileptic drugs. A negative correlation between homocysteine and folic acid concentrations was detected in epileptic patients on anti-epileptic drug. The duration of anti-epileptic drug use was correlated to the decrease of folic acid levels, but not with changes observed in homocysteine, Vitamin B12 and pyridoxal 5'-phosphate levels. No relationship between seizure frequency and homocysteine levels was observed in epileptic patients. Our results confirm that common anti-epileptic drugs has disadvantageous effects on homocysteine status. Because there was no significant change in homocysteine concentrations in epileptic patients who were not receiving an anti-epileptic drug, and no positive correlation between seizure frequency and homocysteine levels, we suggest that increase of homocysteine levels may be due to anti-epileptic drug use, rather than being epileptic in origin. Additionally, the underlying mechanism for homocysteine increase seems to be a decrease of cofactor molecules in patients using carbamazepine and phenytoin (pyridoxal 5'-phosphate and folic acid, respectively). However, changes observed are not related to the alteration in the levels of cofactors and remain unclear in the patients using valproic acid.
authors.affiliation: SSK Tepecik Teaching Hospital, Department of Neurology, Izmir, Turkey. usener2003@yahoo.com
authors.forename: Ufuk
authors.initials: U
authors.lastname: Sener
authors.forename: Yasar
authors.initials: Y
authors.lastname: Zorlu
authors.forename: Oguz
authors.initials: O
authors.lastname: Karaguzel
authors.forename: Ozlem
authors.initials: O
authors.lastname: Ozdamar
authors.forename: Isil
authors.initials: I
authors.lastname: Coker
authors.forename: Murat
authors.initials: M
authors.lastname: Topbas
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D002220:Carbamazepine / Q000009:adverse effects; D016022:Case-Control Studies; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000009:adverse effects; D011732:Pyridoxal Phosphate / Q000097:blood*; D012016:Reference Values; D014635:Valproic Acid / Q000009:adverse effects; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D000927:Anticonvulsants; D006710:Homocysteine; D002220:Carbamazepine; D011732:Pyridoxal Phosphate; D014635:Valproic Acid; D010672:Phenytoin; D005492:Folic Acid; D014805:Vitamin B 12