Antiepileptic Drugs (AEDs), Folate, and Vitamin B12 Deficiency
Antiepileptic drugs (AEDs) are essential for seizure control, but long-term use is associated with alterations in folate and vitamin B12 metabolism, which can affect mood, cognition, and neurologic function.
How AEDs affect folate
Strongest associations are seen with:
- Phenytoin
- Phenobarbital / primidone
- Carbamazepine
- Valproate
Mechanisms include hepatic enzyme induction and accelerated folate turnover.
AEDs and vitamin B12
Some AEDs—particularly phenobarbital, primidone, pregabalin, and topiramate—have been associated with lower B12 levels in observational cohorts.
Homocysteine elevation
Reduced folate and B12 frequently result in elevated homocysteine, reflecting disrupted one-carbon metabolism.
👉 For how these deficiencies interact with depression treatment, see:
“L-Methylfolate (5-MTHF) for Depression: Who Is Most Likely to Respond?”
“B12 deficiency and functional deficiency”
Clinical consequences
- Fatigue and depression
- Cognitive slowing
- Peripheral neuropathy
- Macrocytosis or anemia
FAQ
- Do all AEDs cause deficiencies? No, but many do
- Who needs monitoring? Long-term use, polytherapy, high doses
- Does supplementation worsen seizures? No evidence when used appropriately
Sources
Linnebank M et al., Epilepsia, 2011
Gorjipour F et al., Iran J Neurol, 2013
Bochyńska A et al., Epilepsy & Behavior, 2012
Medical Disclaimer
This article is for educational purposes only and does not replace medical advice. Patients should consult their healthcare provider before making medication or supplement changes.