Understanding MTHFR, the Gene Variant Affecting Up to 35% of People

Most people never think about the MTHFR gene until it turns up as a flag on a genetic test or a term they stumble across online. Tania Elliott, M.D., M.B.A., a board-certified physician in internal medicine and immunology, said the gene plays a quiet but important role in how the body processes folate, and variations in it are far more common than most patients realize.

Elliott has navigated an MTHFR variant herself, an experience that shaped how she now counsels patients on nutrient metabolism, lab testing and the limits of a "normal" result. Below, she explains what MTHFR actually does, how she uncovered her own functional folate deficiency and how patients can cut through the noise in the supplement aisle.

Most people have never heard of MTHFR until they stumble across it online or get a genetic test back with a flag on it. What is it in plain language, and how common is it really?

Tania Elliott, M.D., M.B.A.: MTHFR is a gene that helps your body convert folate, a B vitamin, into its active, usable form. Think of it as a conversion switch. When there's a variation in the gene, that process may work less efficiently. MTHFR variants are common, affecting up to 35% of the population.

You have navigated MTHFR personally. What did that experience teach you about the gap between what standard lab results show and what is actually happening in your body?

TE: This is what happened to me. I got a blood panel from a reputable online company, and it came back that I had the mutation. It didn't say which mutation, though. There are two copies of this gene. Some people have a double mutation, and some only have one, which means they have another working copy and may not be as affected.

My folate levels were normal, but normal levels don't tell anything about the function of folate, meaning whether I was converting it to the active form. Activated folate helps recycle the inflammatory marker homocysteine, so I had to have that level checked, and it was high, meaning my folate wasn't functioning properly.

The supplement aisle is overwhelming, and most patients have no idea what they actually need. How do you help patients cut through the noise and figure out which nutrients are genuinely relevant to their specific situation?

TE: If you have the mutation, or if you aren't sure, consider the methylated forms of B12 and folate, methylcobalamin and methylfolate, as these supplements are already in the active form, ready for your body to use.

I take Pure Encapsulations PureGenomics B-Complex, a comprehensive B vitamin supplement targeting common genetic variations that supports cellular health, DNA synthesis, hormone and neurotransmitter production and energy metabolism. It may be especially relevant for people interested in methylated B vitamins, since it includes L-5-MTHF, the active form of folate, along with forms of B12 that support healthy nutrient metabolism.

Methylated B vitamins keep coming up in conversations about MTHFR and energy metabolism, but most people do not know what methylated means or why it matters. Can you break that down for a nonclinical audience?

TE: "Methylated" may sound complicated, but it simply means the vitamin is already in its active, ready-to-use form. Normally, your body converts nutrients into the forms it can use, and the MTHFR gene plays a role in converting folate. If that process is less efficient, methylated forms like methylfolate, instead of folic acid, and methylcobalamin, or B12, can help provide the active form directly.

A few caveats: methylated vitamins often cost more, and for people without an MTHFR variant, the difference may be minimal, since their bodies handle the conversion process normally. I personally take Pure Encapsulations B-Complex.

Energy and brain fog are two of the most common complaints patients bring to their doctors, and two of the least satisfying to get answers about. Where does nutrient metabolism fit into that picture, and what should patients be asking that they probably are not?

TE: Nutrient metabolism and nutrient deficiencies can impact energy levels and cognition. I always tell my patients to get their nutrients from whole food wherever they can, since the body is better at utilizing them that way. Next, get labs for the big things: B12, folate, ferritin, which is a marker of iron stores, and homocysteine. Talk with your doctor about what the ideal number is. Your labs may come back "normal," which is not the same thing as optimal.

Opt for the methylated forms if you can, though this matters less if you don't have the mutation. Consider a multivitamin if you aren't good about getting enough nutrition from food. If you're eating 30 different fruits and vegetables a week and whole food protein from fish, you should be getting enough, but not everyone is.