Possible Interaction: Valproic Acid and Folate

“Since methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate interconversion and homocysteine metabolism, we addressed the possibility that VPA might have different teratogenicity in Mthfr+/+ and Mthfr+/− mice and that VPA might interfere with folate metabolism through MTHFR modulation.”

“However, long-term exposure to valproic acid (VPA) affected the expression of folate carriers (FOLR1, SLC46A1).”

“ VPA treatment for 24h increased folate receptor-α (FRα) and proton-coupled folate transporter (PCFT) mRNA expression; however, it did not affect reduced folate carrier expression.”

“Patients receiving VPA or LTG had significantly lower serum folate levels in comparison with controls (p<0.001).”

“ Sodium valproate and lamotrigine, commonly used mood stabilizers for the treatment of bipolar disorder, can potentially interfere with folate and homocysteine metabolism.”

“ VPA downregulated levels of superoxide dismutase (SOD), glutathione (GSH), histone deacetylase (HDAC) and folate , and upregulated H(2)O(2) and homocysteine.”

“Chronic treatmennt of rats with sodium valproate caused a decrease in liver folate concentration with concomitant increases in brain and plasma folate concentrations.”

“ VPA considerably reduced maternal plasma folate and B12 concentrations.”

“The mechanism of teratogenicity remains unclear, but it has been hypothesized that VPA interferes with folate metabolism.”

“ Folate concentrations decrease during normal pregnancy and treatment with antiepileptic drugs, including VPA.”