Diet- and valproate-induced transient hyperammonemia: effect of l-carnitine

Abstract

Hyperammonemia is an adverse effect of valproate (VPA) treatment. In particular, transient hyperammonemia has been reported to occur in VPA-treated patients after protein-rich meals. This phenomenon may occur secondary to a VPA-mediated carnitine insufficiency. We sought to confirm that protein ingestion would result in transient hyperammonemia and to determine whether supplementation with l-carnitine would prevent this effect. We studied the effect of consumption of a standardized protein-rich meal (45 g protein) before (phase I) and after (phase II) administration of l-carnitine 50 mg/kg/day for 7 days in 11 epileptic children (13.3 ± 2.3 years of age) receiving VPA. Venous blood was obtained during fasting (baseline) and at 2 and 4 hours after the protein-rich meal for analysis of ammonia (NH 3), and VPA concentrations. Mean VPA trough concentrations did not differ significantly at any time. After protein ingestion, 2-hour NH 3 concentration increase by 86% ( P < .05) from baseline in phase I as compared with a 38% increase in phase II. In both phases I and II, 4-hour NH 3 concentrations decreased toward baseline values. We conclude that (1) modest protein ingestion can result in significant transient increases in NH 3 in VPA-treated children, (2) significant increases may occur in patients with normal fasting NH 3 concentrations, (3) these increases can be significantly attenuated by l-carnitine supplementation, and (4) these changes do not appear to be related to changes in VPA concentration.