When people discover they have a methylation issue like MTHFR, COMT, MTR, or BHMT mutations—maybe through a gene test or blood work—one of the first things they’re told is to take folate and vitamin B12. And yes, these are essential nutrients for methylation, but taking them in isolation is rarely the whole solution.

Methylation is a networked process, not a single switch you can flip with two nutrients. The methylation cycle relies on several cofactors, enzymes, and pathways that all have to work together. If one part of the network is under-functioning—or if something else in the body is creating excess demand—simply adding more folate and B12 may not fix the problem (and in some cases can make symptoms worse).

MTHFR mutations are variants of a specific gene that codes for making the MTHFR enzyme. This enzyme plays an important role in a process called methylation. Methylation is one of three key processes that controls how our genes are expressed. It puts a tiny chemical tag on certain genes (depending on what signals your cells are getting from their external environment) to silence them. Other signals can lead to de-methylation, where methylation takes the tag away, allowing the genes to be expressed.