Effect of Prolonged Anticonvulsant Medication in Epileptic Patients: Serum Lipids, Vitamins B₆, B₁₂, and Folic Acid, Proteins, and Fine Structure of Liver

Abstract

Twenty-seven epileptic patients, most from low socioeconomic groups and aged 15-54 years, were studied for effects of prolonged anticonvulsant medication. They had received the usual doses of phenobarbitone and diphenylhydantoin (PHT) regularly for 3-32 years, with control of seizures, and had not taken any B-vitamins in the year before investigation. Besides reduced serum and cerebrospinal fluid (CSF) folate levels, significantly increased levels of total vitamin B6 in CSF and serum and of vitamin B12 in serum were found in patients as compared with normal healthy subjects. The bone marrow was normoblastic, and significant elevation of serum triglycerides and/or cholesterol was observed in patients. The total protein level was only slightly reduced as compared with that of controls, but there was significant increase in beta-lipoprotein fraction on gel electrophoresis. Plasma proteins concerned with vitamins and lipid transport showed no remarkable change, and no abnormal protein was detected. Although there was no clinical hepatic involvement, liver biopsy performed in 9 of 27 patients revealed fine structural changes in hepatocytes suggestive of varying degrees of drug-induced changes. A ramifying network of short, smooth, endoplasmic cisternae with depleted rough endoplasmic reticulum (RER), distended sinusoids with Kupffer cells, dark shrunken hepatocytes with reduced mitochondria, and increased lipofuscin were observed. This suggested an adaptive response of the liver, a reversible change, possibly related to the increased serum lipids in the same patients.

Carnitine and Liver Functions Assessment in ChildrenTreated with Anticonvulsant Drugs

“…The significantly increased triglycerides values are detected mainly in the carbamazepine treated group (P < 0.05). This finding is in accordance with that of Datsur and Dave [26] . The possible mechanism of the increased level of triglycerides is the inhibition of β-oxidation of fatty acids due to carnitine deficiency and as a result, the fatty acids will be directed to triglyceride synthesis [27] .…”

Antiepileptic drug use for treatment of epilepsy and dyslipidemia: Systematic review

“…Being on phenytoin and phenobarbital was associated with statistically higher levels of total cholesterol (Dastur and Dave, 1987), while higher levels of HDL were found when phenytoin and phenobarbital were used together. (Luoma et al, 1982(Luoma et al, , 1980 On the other hand, being on carbamazepine and valproic acid was associated with significantly lower levels of HDL.…”

Relation between serum vitamin B₁₂ level and duration of treatment with carbamazepine in epilepsy patients

“…17 On the contrary, in a study showed that serum vitamin B12 concentration were elevated in all patients. 11 Increased circulating vitamin B12 level, however, served as a sensitive biochemical index of hepatic damage due to anticonvulsants 18 . Prolonged drug treatment was possibly the cause of the slightly impaired ability of the liver to store vitamin B12.…”