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Alterations in the carnitine metabolism in epileptic children treated with valproic acid
1Department of Pediatrics, College of Medicine, Kyung Hee University, Seoul, Korea.
Insights
Valproic acid (VPA) epilepsy treatment lowers serum carnitine levels. Supplementation with L-carnitine effectively increased carnitine concentrations in patients with hypocarnitinemia.
Area of Science:
- Biochemistry
- Clinical Neurology
- Pharmacology
Background:
- Valproic acid (VPA) is a widely used antiepileptic drug.
- Carnitine plays a crucial role in fatty acid metabolism.
- VPA therapy has been associated with potential carnitine depletion.
Purpose of the Study:
- To investigate serum carnitine levels in epileptic patients treated with VPA.
- To compare carnitine levels between VPA monotherapy and polytherapy groups.
- To explore correlations between carnitine levels, VPA treatment duration, and liver enzymes.
Main Methods:
- Serum concentrations of total, free, and acylcarnitine were measured.
- Forty-one epileptic patients (14 monotherapy, 27 polytherapy) and 41 controls were analyzed.
- Correlations with VPA dosage, treatment duration, and serum GOT/GPT activities were assessed.
Main Results:
- Significantly lower total and free carnitine levels were observed in both VPA monotherapy and polytherapy groups compared to controls.
- No significant difference in carnitine levels between monotherapy and polytherapy groups, though polytherapy patients showed lower levels.
- An inverse correlation was found between serum carnitine and VPA treatment duration; no significant correlation with VPA levels or liver enzymes.
- L-carnitine supplementation significantly increased carnitine concentrations in eleven patients with hypocarnitinemia.
Conclusions:
- Valproic acid treatment, both monotherapy and polytherapy, leads to reduced serum carnitine levels in epileptic patients.
- Longer duration of VPA treatment is associated with lower carnitine concentrations.
- L-carnitine supplementation appears effective in restoring carnitine levels in VPA-treated patients with hypocarnitinemia.
Abstract:
Serum concentrations of total carnitine, free carnitine and acylcarnitine were measured in forty-one epileptic patients treated with valproic acid (VPA). Among them, 14 patients were on VPA monotherapy and 27 were on VPA polytherapy. Forty-one age and sex matched healthy normal controls were also evaluated for carnitine metabolism. The mean total and free carnitine were significantly lower in both the VPA monotherapy and polytherapy groups compared with the controls. However, there were no significant differences in concentrations of carnitine between the VPA polytherapy and VPA monotherapy groups. Patients treated with VPA polytherapy had lower carnitine than those treated with VPA monotherapy. An inverse correlation was found between serum concentrations of carnitine and duration of treatment in patients treated with VPA. However, there was no significant correlations between serum concentrations of carnitine and those of VPA. Also, correlation between serum concentrations of carnitine and the activities of serum GOT and GPT was not significant. After L-carnitine supplementation in eleven patients with hypocarnitinemia, the concentrations of carnitine were significantly increased.