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.
Melegh
B
B
Department of Pediatrics, University Medical School of Pécs, Hungary.
Pap
M
M
Morava
E
E
Molnar
D
D
Dani
M
M
Kurucz
J
J
D000293:Adolescent; D001481:Basal Metabolism / Q000187:drug effects*; D002331:Carnitine / Q000008:administration & dosage / Q000172:deficiency*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004040:Dietary Carbohydrates / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D014635:Valproic Acid / Q000494:pharmacology*
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D014635:Valproic Acid; D002331:Carnitine