Epilepsy treatment by sacrificing vitamin D

Abstract

Epilepsy is one of the most common neurologic disorders in childhood that often requires long term treatment with antiepileptic drugs. Both antiepileptic treatment and the comorbidities associated with epilepsy have a negative impact on bone health in growing children. Given the fact that vitamin D deficiency is a major public health problem worldwide, clinicians caring for children with chronic diseases should be aware of effects of the medication on the bone metabolism. Yet, vitamin D deficiency due to antiepileptic treatment is an overlooked issue among neurologists. In this review, we briefly describe vitamin D metabolism and the effect of vitamin D in the brain. We also discuss the literature in terms of vitamin D deficiency and antiepileptic treatment in the pediatric population.

Keywords::

• antiepileptic therapy
• bone health
• children
• epilepsy
• vitamin D deficiency

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

• Long-term antiepileptic therapy has been associated with increased rates of bone fractures and abnormalities in bone and mineral metabolism.

• Anticonvulsant effect of vitamin D was reported in a small pilot study conducted in patients with pharmacoresistant epilepsy and low vitamin D levels.

• Calcitriol is the most potent form of vitamin D, and its biological acts are mediated mainly through the vitamin D receptor (VDR), a member of the steroid/thyroid/VDR gene superfamily of the nuclear-transcription-activating factors.

• The key enzyme for degradative hydroxylation of both calcitriol and calcidiol is mitochondrial 25-OHD-24 hydroxylase, an inducible cytochrome P450 enzyme.

• A multicenter cross-sectional study has demonstrated that 13.3% of otherwise healthy children who received antiepileptic monotherapy had severe vitamin D deficiency.

• Limited mobilization and disability, low dietary intake of vitamin D, intractable epilepsy and polytherapy are the main factors that contribute to vitamin D deficiency and poor bone health in children receiving antiepileptic medication.

• For a child on antiepileptic treatment, a more active lifestyle that includes regular outdoor activities and consumption of vitamin D-rich diet (dairy products and fatty fish) should be encouraged.

• Many antiepileptic drugs, including phenytoin, carbamazepine, phenobarbital and primidone, are inducers of hepatic P450 system. Increased hepatic metabolism of vitamin D leads to enhanced bone resorption.

• Patients with BsmI polymorphism of the VDR who receive antiepileptic therapy have lower serum 25-OH vitamin D levels.

• There are scarce literature regarding ‘newer’ antiepileptic drugs and vitamin D status.