Does valproic acid cause carnitine deficiency?

Carnitine is an essential amino acid necessary in beta-oxidation of fatty acids and energy production in cellular mitochondria. It has been hypothesized that valproic acid may induce a carnitine deficiency in children and cause nonspecific symptoms of deficiency, hepatotoxicity, and hyperammonemia.

What causes low carnitine levels?

Carnitine deficiency results from inadequate intake of or inability to metabolize the amino acid carnitine. It can cause a heterogeneous group of disorders. Muscle metabolism is impaired, causing myopathy, hypoglycemia, or cardiomyopathy. Infants typically present with hypoglycemic, hypoketotic encephalopathy.

How does valproic acid cause hyperammonemia?

The mechanism is decreased production of mitochondrial acetyl CoA, which causes decrease in N -acetylglutamate, an activator of carbamoyl phosphate synthetase. Thus, patients with partial enzyme deficiencies may be at increased risk of developing symptomatic hyperammonemia during treatment with valproate.

What is valproic acid toxicity?

Manifestations of acute valproic acid toxicity are myriad, and reflect both exaggerated therapeutic effect and impaired intermediary metabolism. Central nervous system depression is the most common finding noted in overdose, and may progress to coma and respiratory depression. Cerebral edema has also been observed.

When to take carnitine For valproic acid treatment?

Carnitine supplements in the prevention of valproic acid toxicity. Until further data become available, L-carnitine supplementation may be recommended in those children on VPA therapy at greatest risk for hepatotoxicity (<2 years of age, more than one anticonvulsant, poor nutritional status, ketogenic diet).

Can a carnitine deficiency cause acute VPA intoxication?

Some data suggest that VHT and VHE may be promoted by carnitine deficiency. Acute VPA intoxication also occurs as a consequence of intentional or accidental overdose and its incidence is increasing, because of use of VPA in psychiatric disorders.

Are there any studies on oral L-carnitine?

Several studies or isolated clinical observations have suggested the potential value of oral L-carnitine in reversing carnitine deficiency or preventing its development as well as some adverse effects due to VPA.

Is there a link between carnitine and VHE?

Some data suggest that VHT and VHE may be promoted either by a pre-existing carnitine deficiency or by deficiency induced by VPA per se. Acute VPA intoxication also occurs as a consequence of intentional or accidental overdose. Its incidence is increasing [ 2 – 5 ], probably because of the use of VPA in psychiatric disorders.