The Potential Mechanisms of Effect of Valproic Acid on Lipid Profiles: An Updated Review

Abstract

Introduction. Valproic acid is commonly used for the treatment of epilepsy, psychiatric disorders such as bipolar disorders, anxiety and prophylaxis migraine. Long-term use of valproic acid is related with metabolic disorders such as the increase of body weight and changes of lipid profiles which are contributed to cardiovascular events, however, these associations remain unclear, furthermore, the mechanisms of these effects have not been fully elucidated. Aim. To summarize and discuss the potential mechanisms of valproic acid-related changes of lipid profiles so as to get a better understanding of the side effects of valproic acid on lipid metabolism. Methods. Literature reviews were conducted through the survey of the literature utilizing the Pubmed electronic databases, with the aim to identify all literature regarding the metabolic effects of valproic acid. This review has been written to summarize the latest evidence of valproic acid's effects on lipid profiles. Review and Discussion. The possible mechanisms of valproic acid-related changes of lipid profiles could be through insulin resistance and hyperinsulinemia in several ways, resulting in the alteration of lipogenesis and clearance of triglyceride and lipoproteins. Conclusion. The effect of valproic acid on lipid profiles is complex and there is a need for further investigation. Consequently the monitoring and follow up of lipid profiles from patients prescribed valproic acid is recommended.

Evaluation of Metabolic Parameters on Use of Newer Antiepileptics Versus Conventional Antiepileptics in Patients of Generalised Tonic-Clonic Seizure: An Observational Study

“…The mechanism behind the lipid profile changes due to valproic acid is still unclear. A possible mechanism may be insulin resistance and hyperinsulinemia, resulting in impaired lipid transport and lipogenesis [17].…”

“…The mechanism behind the lipid profile changes due to valproic acid is still unclear. A possible mechanism may be insulin resistance and hyperinsulinemia, resulting in impaired lipid transport and lipogenesis [ 17 ]. Another possible mechanism may be the induction of cytochrome p (CYP) enzymes that play a role in metabolism and the biosynthesis of cholesterol.…”

Long-Term Effects of Antiseizure Medications

“…21 VPA has multiple metabolic effects, including adiponectin and glucose transporter inhibition that raise insulin levels, protein binding which increases the circulating free fatty acids in serum, and a hypothalamic-mediated effect on appetite which indirectly raises lipid fractions. 22 Triglycerides are often elevated in valproate users as part of the metabolic syndrome. Therefore, it follows that with longer durations of therapy, multifactorial processes will counteract the initial enzyme-inhibiting effects of VPA on cholesterol.…”

effect of patient’s characteristics on CYP2C19 polymorphisms based on weight and gender groups of epileptic seizure patients taking divalproex sodium

“…A study conducted by Verotti et al (2011) and El-Khatib et al (2007) reported that a significant increase in body weight (≥ 5 kg) occurred in 43.6% of women and 23.5% of men who received VPA therapy. The mechanisms of valproic acid-related alter of lipid profiles through the insulin resistance and hyperinsulinemia (Jaeri and Islamiyah, 2018).…”