Evidence for a potential protective effect of carnitine-pantothenic acid co-treatment on valproic acid-induced hepatotoxicity

Abstract

Valproic acid is approved for treatment of seizures and manic episodes of bipolar disorder, and continues to be one of the most commonly prescribed antiepileptic drugs in the world. Hepatotoxicity is a rare but serious side effect resulting from its use, particularly in young patients. This adverse effect does not display normal dose–response curves and can be lethal in children. A review of the purported mechanisms of action suggest hepatotoxicity results from increased oxidative stress, caused by a reduction in beta-oxidation and an increase in activation of certain metabolizing enzymes. There is also evidence that both carnitine and pantothenic acid are involved in the regulation of valproic acid-induced hepatotoxic processes, and clinical evidence has shown that treatment with either compound shows protective effects against hepatotoxicity. These results suggest a potential increase in protective effects with cotreatment of carnitine and pantothenic acid.

Keywords::

• beta-oxidation
• carnitine
• coenzyme A
• CYP2A6
• CYP2B6
• CYP2C9
• CYP2C9*1/*1 genotype
• hepatotoxicity
• metabolic activation
• oxidative stress
• pantothenic acid
• valproic acid

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• In the case of valproic acid-induced hepatotoxicity in young children, the research emphasis should be directed to clinical outcome rather than to continued efforts on finding the putative reactive metabolites.

• Dietary supplements used to treat or ameliorate a drug-induced adverse condition should be subject to a standardized review, possibly similar to generally recognized as safe procedures at US FDA.

• Consumers, and particularly parents of young children, should have access to standardized dosage forms when dietary supplements are suggested as part of a medical treatment.

• Incentives should be created to reward those groups that resolve drug-induced toxicities with dietary supplements or naturally derived products.

Notes