L-carnitine replacement therapy in chronic valproate treatment

Area of Science:

• Biochemistry
• Pediatric Neurology
• Pharmacology

Background:

• Chronic valproic acid (VPA) treatment in epileptic children is associated with carnitine insufficiency.
• Carnitine deficiency can impact metabolic processes, including ketogenesis.

Purpose of the Study:

• To investigate the effect of L-carnitine supplementation on carnitine status in epileptic children on VPA therapy.
• To explore the relationship between carnitine levels, VPA treatment, and metabolic parameters like ketogenesis.

Main Methods:

• A 14-day open-label study involving ten epileptic children treated with VPA.
• Measurement of plasma and urinary carnitine levels, beta-hydroxybutyrate, free fatty acids, and triglycerides before and after L-carnitine administration.
• Comparison with age- and sex-matched control subjects.

Main Results:

• VPA-treated children exhibited carnitine insufficiency prior to supplementation.
• L-carnitine administration significantly increased plasma free and esterified carnitines and urinary excretion of esterified carnitines.
• The depressed level of beta-hydroxybutyrate (hypoketonemia) remained unaffected by L-carnitine supplementation.
• Plasma VPA levels and seizure control were unchanged by carnitine treatment.

Conclusions:

• L-carnitine supplementation effectively replenishes carnitine levels in epileptic children treated with VPA.
• Carnitine insufficiency in VPA-treated children is not directly linked to the observed hypoketonemia.
• VPA's effect on fasting ketogenesis does not appear to be mediated by alterations in lipolysis or hepatic hormonal control.