Everything You Need To Know, From Experts

Before we dive into the genetic variants and what they mean, let’s talk about MTHFR itself and its role in the body when everything is functioning optimally. 

MTHFR, or methylenetetrahydrofolate reductase, is an enzyme that converts dietary folate (from foods like leafy greens) and folic acid (from fortified foods and supplements) into a bioactive, methylated form called 5-methyltetrahydrofolate (5-MTHF).

This activated folate acts as a highly effective and required methyl donor and plays a key role in a biochemical process called methylation—i.e., the transfer of methyl groups (simple structures of one carbon and three hydrogen molecules) to and from different molecules to support overall health.*

Specifically, 5-MTHF donates a methyl group to the amino acid homocysteine to convert it to the amino acid methionine (building block for proteins throughout the body); and methionine, in turn, can be activated to form S-adenosylmethionine (SAM-e), which travels around the body donating methyl groups to a variety of acceptors and helping regulate the activity of our neurological, cardiovascular, reproductive, and detox systems in the process. 

Holistically, this process or path is known as the methylation cycle. And as Ashley Jordan Ferira, Ph.D., RDN, mbg’s vice president of scientific affairs, explains, “that first step, bioactive folate donating a methyl group to transform homocysteine to methionine, is a rate limiting step.”

What does that mean? Ferira shares more: “It means that without adequate methylated folate (5-MTHF) around, homocysteine can’t move along to its next critical step. It can build up, and the rest of the methylation cycle is also slowed, deprived, or halted. As it turns out, that’s a huge deal for your health.”*

So what’s the big deal? Methylation is a foundational process in the body (i.e., our cells) that takes place approximately one billion times per second and plays a role in just about everything—from keeping homocysteine levels in check (which is directly relevant to our cardiovascular and neurological health) to manufacturing important molecules like neurotransmitters and the antioxidant glutathione to influencing gene expression, says functional medicine physician Robert Rountree, M.D. (Learn more about methylation here.)

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