The Effect of Carnitine Supplementation on Hyperammonemia and Carnitine Deficiency Treated with Valproic Acid in a Psychiatric Setting

Masaru Nakamura, Takahiko Nagamine
Innovations in Clinical Neuroscience 2015, 12 (9-10): 18-24

OBJECTIVE: The aim of this study was to investigate the effect of levocarnitine (active isoform of carnitine, L-Carnitine) supplementation on serum ammonia and carnitine levels simultaneously, and their clinical outcomes in valproic acid-treated psychiatric subjects.

DESIGN: This was a propsective study of 22 psychiatric patients.

METHOD: A fixed dose of levocarnitine was coadministrated over a period of three months in subjects with valproic acid-induced hyperammonemia. Serum ammonia, valproic acid, and carnitine concentrations were measured, and psychiatric symptoms were recorded at baseline and one, two, and three months. Sequential change of the levels of serum ammonia, valproic acid, free carnitine, acylcarnitine, total carnitine, ratios of acylcarnitine/free carnitine, and the scores of Brief Psychotic Rating Scale, Clinical Global Impression-Severity scale, and the Global Assessment of Functioning scale were compared within total subjects and two groups divided by the effectiveness of levocarnitine supplementation against baseline hyperammonemia.

RESULTS: Within total subjects, free carnitine, acylcarnitine, and total carnitine levels were significantly increased without statistical change in serum ammonia, valproic acid levels, and acylcarnitine/free carnitine ratio, while a part of Brief Psychotic Rating Scale scores was decreased. Acylcarnitine levels were significantly increased at all points in the levocarnitine effective group and not in the noneffective group. Acylcarnitine/free carnitine ratio increased in the levocarnitine effective group and decreased in the noneffective group, which was confirmed by negative correlation between the ratio of serum ammonia levels at three months to serum ammonia levels at baseline and the ratio of acylcarnitine/free carnitine levels at three months to acylcarnitine/free carnitine levels at baseline.

CONCLUSION: In valproic acid-treated psychiatric patients, carnitine supplementation resulted in overall improvement in mental status. Improvement of hyperammonemia and carnitine deficiency in this group may be related to mitochondrial function.

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