Diet- and valproate-induced transient hyperammonemia: Effect of L-carnitine

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 mould 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 (NH3), and VPA concentrations, Mean VPA trough concentrations did not differ significantly at any time, After protein ingestion, 2-hour NH3, concentration increased 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 NH3 concentrations decreased toward baseline values, We conclude that (1) modest protein ingestion can result in significant transient increases in NH3 in VPA-treated children, (2) significant increases may occur in patients with normal fasting NH3 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. (C) 1997 by Elsevier Science Inc. All rights reserved.