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MTHFR, Homocysteine & Epilepsy: What the Research Says

If you’ve heard people link MTHFR to epilepsy, here’s the short science thread you can share.

MTHFR

1) MTHFR -> higher homocysteine can be pro-convulsant
A well-studied MTHFR variant (C677T) is associated with moderately higher homocysteine levels. Homocysteine has pro-convulsant activity, which helps explain why this genetic variant has been explored as a biologically plausible risk factor in seizures/epilepsy.

Epilepsy

2) People with epilepsy often show higher homocysteine & lower folate/B12
Multiple clinical studies report that patients with epilepsy, especially those on certain anti-epileptic drugs (AEDs), tend to have higher homocysteine and lower folate/B12 compared to controls. Some AEDs interfere with folate/B12 status, which can drive homocysteine up.

MTHFR + AEDs:

3) MTHFR + AEDs: a double hit on methylation
Research in adults and children shows that AED use is a risk factor for hyperhomocysteinemia, and that folate/B12 levels can drop on many common AEDs (notably with exceptions like levetiracetam/benzodiazepines). In some cohorts, homocysteine elevations were linked to endothelial dysfunction and worse vascular markers an added reason to monitor.

Supplementation

4) Supplementation can lower homocysteine (clinical data)
Randomized and observational work indicates that adding folate and vitamin B12 to AED therapy is a safe, low-cost way to reduce homocysteine in many patients. That doesn’t replace medical care, but it shows the pathway is modifiable.

Homocysteine and seizure control

5) Homocysteine and seizure control
Some studies suggest biology beyond “just a blood test.” For example, one cohort found MTHFR C677T status related to seizure control among epileptic patients with hyperhomocysteinemia; others have reported that drug-resistant epilepsy groups tend to show higher homocysteine and lower folate/B12 than well-controlled groups. These are associative findings, but they point to something real happening in the methylation axis.

Takeaway (not medical advice)

• MTHFR variants (especially C677T) can raise homocysteine.

• AEDs may further lower folate/B12 → pushing homocysteine higher.

• Lowering homocysteine (diet, folate/B12 under clinician guidance) is feasible and may support overall neurologic and vascular health.

Always discuss testing and supplementation with your neurologist/GP especially if you or your child have epilepsy or are on AEDs

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