Why Methylated B12 Is Often Paired With L-Methylfolate — Especially With Metformin or AEDs
B12 and folate are partners in one-carbon metabolism, essential for neurotransmitter synthesis, DNA repair, and neurologic function.
Using folate without ensuring adequate B12 can reduce effectiveness and mask deficiency.
Why methylated B12 matters
L-methylfolate donates methyl groups, but B12 is required to complete the cycle. Without adequate B12, methylation stalls.
Metformin and B12 deficiency
Metformin interferes with calcium-dependent absorption of the B12–intrinsic factor complex, leading to gradual depletion—even when serum levels appear normal.
The American Diabetes Association recommends considering periodic B12 monitoring in long-term metformin users.
Other medications that lower B12
- Proton pump inhibitors
- H2 blockers
- Certain AEDs (phenobarbital, topiramate)
👉 For AED-specific risks, see:
“Antiepileptic Drugs (AEDs), Folate, and B12 Deficiency.”
“L-methylfolate for depression”
FAQ
- If my B12 is normal, can I still be deficient? Yes—functional deficiency is possible
- Why pair B12 with L-methylfolate? To complete methylation cycles
- Which labs help most? Serum B12, MMA, homocysteine
Sources
Bauman WA et al., Arch Intern Med, 2000
American Diabetes Association, Standards of Care, 2025
O’Leary F & Samman S, Nutrients, 2010
Medical Disclaimer
This content is educational and not medical advice. Always consult your healthcare provider before starting or changing supplements or medications.