Methylfolate vs Folic Acid: Which Should You Take?

Some prenatals advertise methylfolate instead of folic acid, often with a mention of the MTHFR gene. The public-health guidance is simpler than the marketing: what matters most is getting enough folate early, and folic acid is the form with the proof.

Folic acid vs methylfolate: what is the difference?

Folate is a B vitamin. Folic acid is the synthetic form used in supplements and fortified foods such as breakfast cereals.¹ Methylfolate (L-methylfolate, or 5-MTHF) is another form that some supplements contain instead of folic acid, and people with MTHFR variants are sometimes told to take it.²

The key fact: folic acid is the only type of folate shown to help prevent neural tube defects (NTDs), birth defects of the brain and spine that form in the first weeks of pregnancy, often before you know you are pregnant.¹²

How much folic acid do you need before pregnancy?

The CDC recommends 400 mcg of folic acid every day for everyone who could become pregnant, starting at least one month before conception and continuing through pregnancy.¹ The US Preventive Services Task Force gives folic acid its highest grade (A) and recommends a daily supplement with 400 to 800 mcg for anyone planning to or able to become pregnant.³ ACOG also encourages folic acid as part of prepregnancy care.⁵

If you have had a pregnancy affected by an NTD, the CDC recommendation is 4,000 mcg a day, and you should talk to your doctor first.¹ Your doctor may also suggest more for other health conditions.²

Does folic acid help you get pregnant?

It is recommended to prevent birth defects, not to help you conceive, but there is some supportive observational evidence. A Harvard review of diet and fertility found supplemental folic acid has been consistently linked to a lower frequency of infertility, a lower risk of pregnancy loss and better infertility treatment outcomes.⁶ Those are associations from cohort studies, so the evidence grade is low.

What about MTHFR?

MTHFR variants are common. The CDC says more people in the US have one or two copies of the MTHFR C677T variant than do not.² The CDC’s position is clear:

• People with an MTHFR variant can process all types of folate, including folic acid.²
• Common MTHFR variants are not a reason to avoid folic acid.²
• 400 mcg of folic acid daily raises blood folate whatever your genotype. People with two copies (TT) have blood folate only about 16% lower on average than people with none, given the same amount.²
• The claim that people with MTHFR variants must take 5-MTHF instead of folic acid is, in the CDC’s word, not true.²

The American College of Medical Genetics and Genomics (ACMG) reached a related conclusion about testing. Earlier theories linked MTHFR to blood clots and recurrent pregnancy loss, but later meta-analyses did not support the clot link, and ACMG concluded MTHFR polymorphism testing has minimal clinical utility and should not be ordered as part of a routine thrombophilia evaluation.⁴ It issued a 2020 addendum under the same title, “lack of evidence for MTHFR polymorphism testing.”⁴

Methylfolate vs folic acid: the evidence at a glance

Does folic acid help male partners?

Not as a fertility supplement. In the FAZST trial, 2,370 male partners of couples seeking fertility treatment took 5 mg of folic acid with 30 mg of zinc, or placebo, for six months. Semen quality and live birth rates did not improve (34% vs 35%).⁸ Folic acid recommendations are about preventing birth defects, so they apply to the person who could become pregnant.

So, which should you take?

Folic acid is the evidence-based choice. A prenatal or supplement with 400 to 800 mcg of folic acid covers the recommendation.³ A methylfolate prenatal is not harmful and can be a fine product, but its folate form has not been shown to prevent NTDs. If you prefer methylfolate, consider a product that also contains folic acid, or ask your doctor.

Supplements are not FDA-approved: by law the FDA does not approve them or their labels before they are sold.⁷ So the form on the front of the bottle matters less than the dose on the back and whether the product is third-party tested.

What to do now

Start a prenatal with folic acid at least a month before you begin trying.¹ When you choose one, check the folate form, the dose and whether it has third-party testing. Then work through the rest of our preconception checklist. Folate is not the only nutrient to check on a prenatal label: see choline before pregnancy. Everything else for this stage is in the Prepare hub.