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.