What Are Methylated Vitamins?

Choosing vitamins these days can feel more complicated than it needs to be. There’s unending information, conflicting opinions, multiple forms of the same nutrient, and no shortage of trending health claims. During the prenatal, perinatal, and postpartum years, that noise can feel even louder, and the stakes even higher—these windows require key nutrients to support maternal and fetal health, and can have lasting long-term effects on both mom and babe. 

One such topic? Methylated vitamins, especially when it comes to a couple of key pregnancy must-haves, like Folic Acid. Let’s break down what methylation actually means and why methylated nutrients are included in some supplements (including prenatals).

We get our nutrients from food and supplements, but some nutrients need to be metabolized and converted in the body so that they can be used. The form we consume isn’t necessarily the most bioavailable form for our body, and so they’re converted to be more usable. 

This is especially true for:

• Folate
• Vitamin B12
• Choline
• Betaine
• Methionine
• other B vitamins 

Methylation is that conversion. It’s a biochemical process where methyl groups (which have 1 carbon atom bonded to 3 hydrogen atoms, known as CH3) are added to the nutrients listed above so they can support DNA, proteins, or other molecules, ensuring your body works properly. 

Methylation is helped along by S-adenosylmethionine (SAM), known as the universal methyl donor, which makes methylation possible, but also requires enough methylated Folate, B12, and B6 to work well. This all happens in the body naturally, but some people have trouble converting Folic Acid to Methylated Folate (more on that shortly), which makes the natural methylation that happens in the body less efficient. 

Methylated vitamins have already undergone the process of adding the methyl donor and don’t require further conversion in the body. Simply, methylated vitamins come pre-converted, so your body does less work to make the nutrients useful. 

The methylated form of Folate is L-5-methyltetrahydrofolate (5-MTHF). Folic Acid, the synthetic form found in most supplements, is inactive and must be converted in the body to 5-MTHF. 

The process is multi-step:

1. Folic Acid is first converted to dihydrofolate
2. Then dihydrofolate to tetrahydrofolate
3. And finally tetrahydrofolate to 5-MTHF

This conversion happens primarily in the liver and is dependent on enzymes like dihydrofolate reductase (DHFR) and Methylenetetrahydrofolate Reductase (MTHFR).

Methylated vitamins like methylfolate (5-MTHF) and methylcobalamin (Vitamin B12) are generally considered more bioavailable compared to their non-methylated counterparts. The main benefit of methylated forms is that they are already in their active state and can be more readily used by the body. This is especially true for individuals with genetic variations that affect their ability to convert non-methylated forms efficiently (more on this later).

For the most part, yes. Methylated B-vitamins are generally safe for most people—always talk to your health care provider before starting a new supplement, to ensure it’s a safe option for you. Some populations (including those with or at higher risk of cancer, or who are taking immunosuppressant or antimicrobial medication) will need to be very careful of getting too much of methylated doses.

The activation of B-vitamins requires enzymes to convert them into their bioavailable, methylated forms. These enzymes are genetically coded and mutations can be tested through simple blood or saliva DNA tests. While methylation disorders (where your body isn’t converting vitamins effectively into their methylated forms and therefore you get less of the dose) in the general population are low, there are certain groups at higher risk. For reproductively-aged females, polymorphisms (or genetic variations) in the methylenetetrahydrofolate reductase (MTHFR) gene are high, impacting up to 60% of the population. And we know that getting enough Folate is essential for neural tube defect (NTD) prevention and the health of an ongoing pregnancy.

Not necessarily. It’s important to note that research still supports the intake of at least 400 mcg of Folic Acid for the prevention of neural tube defects (NTDs). Large-scale trials demonstrating the same effect for methylfolate are lacking (meaning you shouldn’t just swap one for the other). Many countries require foods to be fortified with Folate, which has significantly reduced Folic Acid deficiency rates and the incidence of NTDs since the program started in the 1990s. Supplementation of at least 400 mcg Folic Acid, should be started around 2 to 3 months before trying to conceive to make sure there’s enough in your system before pregnancy is achieved. If you’re concerned about gene status, and trying to conceive or pregnant, look for a prenatal that includes both the doctor-recommended and study-backed dose of Folic Acid (400 mcg) and a dose of 5-MTHF so that you’re covered.