Carnitine-dependent changes of metabolic fuel consumption during long-term treatment with valproic acid

Energy metabolism was measured in children receiving long-term treatment with valproic acid. In 8 of 10 randomly selected subjects, the resting respiratory quotient was higher than in age- and sex-matched control subjects (0.91 ± 0.01 vs 0.87 ± 0.01; p <0.05). A shift was observed in fuel consumption, and a significant reduction was found in the amount of fats oxidized (0.68 ± 0.23 vs 1.18 ± 0.18 gm · kg^-1 · day^-1), which was accompanied by increased utilization of carbohydrates (5.31 ± 0.79 vs 3.81 ± 0.39 gm · kg^-1 · day^-1) in comparison with the control subjects. The resting total energy expenditure was not affected by the treatment. The children with an altered energy consumption pattern (n = 8) received carnitine supplementation for a month; the respiratory quotient then decreased (0.87 ± 0.02), the oxidation of fats increased (1.42 ± 0.25), and the consumption of carbohydrates decreased (3.87 ± 0.79), but no changes in resting energy expenditure were observed. We conclude that carnitine depletion, a known adverse effect of valproic acid administration, may result in inhibited fatty acid oxidation, leading to a shift of substrates utilized from fats to carbohydrates. (J PEDIATR 1994;125:317-21).