Health QuestionsCategory: MedicationsAbstract:  AED’s effect on folic acid, B6/12
gretl asked 3 years ago

New study, Pubmed abstract:

Effects of common anti-epileptic drug monotherapy on serum levels of homocysteine, Vitamin B12, folic acid and Vitamin B6.
Sener U, Zorlu Y, Karaguzel O, Ozdamar O, Coker I, Topbas M.
SSK Tepecik Teaching Hospital, Department of Neurology, Izmir, Turkey.

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.
Seizure. 2006 Jan 13; [Epub ahead of print]

And in a related study, Pubmed abstract:

Executive dysfunction in hyperhomocystinemia responds to homocysteine-lowering treatment.
Boxer AL, Kramer JH, Johnston K, Goldman J, Finley R, Miller BL.
Memory and Aging Center, Department of Neurology, UCSF, San Francisco, CA 94143-1207, USA.

An elevated serum homocysteine level is a risk factor for the development of cognitive impairment. Reported is a late-onset case of hyperhomocystinemia due to a vitamin B12 metabolic deficit (cobalamin C) with cognitive impairment, primarily in frontal/executive function. After homocysteine-lowering therapy, the patient’s functional and neuropsychological status improved in conjunction with a decrease in leukoariosis on his MRI scan. These findings suggest that homocysteine-related cognitive impairment may be partially reversible.
Neurology. 2005 Apr 26;64(8):1431-4.

Might be worth discussing with our doctors.

1 Answers
StrungOutOnLife answered 3 years ago

Re: Abstract:  AED’s effect on folic acid, B6
It looks like valproate might actually lower homocysteine. It says that here, too, in a study where lamotrigine was found not to affect it either way. This one here and this one and this one disagree (on the matter of valproate and its homocysteine decreasing effects, not on lamotrigine and its lack of action in that department).
ETA: If you “ethnic Omani” as defined by the authors of Hereditary thrombophilia in ethnic omani patients, and you have had deep vein thrombosis and/or pulmonary embolism then you should really talk to your doctor if you take anticonvulsants.

Of these patients, 43.58% had either or both the hyperhomocysteinemic mutations studied, whereas in 38.46% of these patients, no underlying cause for thrombophilia could be documented.

ETA2: Holy crap:
Elevated homocysteine levels in euthymic bipolar disorder patients showing functional deterioration
Homocysteine and B Vitamins Relate to Brain Volume and White-Matter Changes in Geriatric Patients With Psychiatric Disorders
High homocysteine serum levels in young male schizophrenia and bipolar patients and in an animal model.