Methylation Cycle
Folate + Vitamin B12 (Cobalamin)
Folate and B12 are paired cofactors in methylation — supplementing one without the other can mask a deficiency of the other.
Vitamin
Essential B vitamin for DNA synthesis, cell division, and methylation. Critical during pregnancy.
Full Folate profile →Vitamin
An essential water-soluble vitamin required for red blood cell formation, neurological function, and DNA synthesis. Cyanocobalamin is a stable synthetic form commonly used in supplements.
Full Vitamin B12 (Cobalamin) profile →Why they work together
Both vitamins are essential for the methylation cycle (converting homocysteine to methionine) and DNA synthesis. They interact such that adequate folate can mask the anemia of B12 deficiency — blood cell production keeps up, but B12's separate neurological role continues to degrade. This is why high-dose folic acid supplementation without B12 carries a documented risk of irreversible nerve damage in B12-deficient users. Supplementing them together ensures both cycle cofactors are present, and the folate never masks a progressing B12 deficiency.
How to dose them
400 mcg methylfolate (or folic acid) + 500–1,000 mcg methylcobalamin B12 daily. Many multivitamins include both at appropriate doses. For MTHFR variant carriers (40% of population), methylfolate form specifically; cyanocobalamin B12 works for most but methylcobalamin is preferred.
Evidence
Mechanism is textbook biochemistry. The masking phenomenon led to US fortification limits on folic acid specifically because of B12 deficiency masking concerns in unsupervised populations.
Watch-outs
Methotrexate (for rheumatoid arthritis, psoriasis, some cancers) is a folate antagonist — supplementing folate requires physician coordination. High-dose folic acid without B12 is the classic configuration to avoid. Pernicious anemia (autoimmune B12 malabsorption) requires injectable B12, not oral.
Next steps
Educational only. Synergy pairs are not prescriptions. Run any new supplement combination past your clinician if you take prescription medication.