Methylation is an extremely important biochemical reaction that’s happening every second in every cell of your body. On the cellular level, methylation is the process of transferring a methyl group (CH3) to a molecule, which activates the molecule so it can be used by the body. For example, attaching a methyl group to folate transforms it into the active form known as L-5-MTHF (L-methylfolate), which is the predominant form of folate found in the body and the only form that can cross the blood-brain-barrier. Likewise, adding a methyl group to homocysteine (a marker of inflammation and cardiovascular disease) converts it back into methionine, a harmless amino acid. The addition and removal of methyl groups to and from DNA are responsible for turning genes on and off. People with the MTHFR gene mutation (especially the C677T variety) can have significant reductions in methylation (even if they take plenty of folate) and may benefit from supplementing with activated folate, B12 and other methyl-supportive nutrients. When you have two copies of the MTHFR gene (homozygous) it becomes even more important to provide methylation support for your body, however, taking high doses of methylfolate can lead to over methylation. Common symptoms of too much methylation support include headaches, irritability, insomnia, runny nose, body pain, and itchy skin. L-5-methylfolate (L-5-MTHF) requires no additional metabolic steps to be used by the body, thus it is often the preferred choice for those with absorption or metabolic defects. Folinic acid (not folic acid) quickly converts to L-methylfolate as needed in the body, but is not “pre-methylated.” Folinic acid may be easier for individuals who are sensitive to methylated nutrients to tolerate than supplemental L-methylfolate.