Carnitine levels in valproic acid-treated psychiatric patients: a cross-sectional study.
BACKGROUND
Carnitine facilitates the transport of long-chain fatty acids across the mitochondria for beta oxidation, and the removal of potentially toxic acylcoenzyme-A metabolites from the inner aspect of mitochondrion as acylcarnitines. Previous studies suggest a significant decrease in carnitine concentrations and changes in the ratio of acylcarnitine to free carnitine in seizure-disoriented patients treated with valproic acid (VPA), which may lead to clinical manifestations of carnitine deficiency. This study sought to explore whether the same decrease in plasma free carnitine and increase in acylcarnitines are seen when VPA is used in the treatment of patients with psychiatric disease.


METHODS
Thirty psychiatric patients treated with VPA for at least six months were selected for the study and granted informed consent for participation. Exclusion criteria included liver disorder or pancreatitis, metabolic defects known to affect plasma carnitine levels, or noncompliance with VPA regimen. Plasma free carnitine, total carnitine, VPA, and amylase levels were determined, and liver function tests (LFTs) were performed. Pearson correlations were conducted between VPA levels, levels and ratios of carnitines, as well as LFTs and amylase levels.


RESULTS
Plasma free and total carnitine levels were lower than the reported normal range for the laboratory performing the assay, and the ratio of acylcarnitine to free carnitine was increased. There was a significant positive correlation of VPA levels and acylcarnitine-free carnitine ratio, a trend toward significance between VPA levels and acylcarnitine levels, and a marginal negative correlation between VPA levels and free carnitine levels. VPA levels correlated also with several LFTs and acylcarnitine levels. Octanoyl carnitine and acylcarnitine levels, as well as acylcarnitine-free carnitine and octanoyl-free carnitine ratios, correlated significantly with amylase levels.


CONCLUSIONS
Although the study was limited by a cross-sectional design without direct control comparison, the findings suggest that patients with various psychiatric conditions treated with polypharmacy that includes VPA may have lower plasma carnitine levels than would be expected in healthy controls.
Department of Psychiatry, College of Medicine, University of Arizona Health Science Center, 1501 N. Campbell Avenue, 7-OPC, Tucson, AZ 85724, USA. fmoreno@u.arizona.edu
Francisco A
FA
Moreno
Helen
H
Macey
Brian
B
Schreiber
D000328:Adult; D000368:Aged; D000681:Amylases / Q000097:blood; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood* / Q000172:deficiency* / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D001523:Mental Disorders / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D014635:Valproic Acid / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000927:Anticonvulsants; C116917:acylcarnitine; D014635:Valproic Acid; D000681:Amylases; D002331:Carnitine