Methylfolate: what it is, who it suits, and how to choose a supplement
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- L-methylfolate capsule with the amount shown in mcg DFE. Best for: Adults who prefer the 5-MTHF form after checking with their doctor. See options on Amazon
- Methylfolate combined with vitamin B12 (methylcobalamin). Best for: People who want folate and B12 in one product. See options on Amazon
- Prenatal vitamin that includes folic acid. Best for: Anyone who could become pregnant, including people with an MTHFR variant. See options on Amazon
- Folic acid 400 mcg tablet. Best for: People who simply need to meet the RDA, including MTHFR carriers. See options on Amazon
What methylfolate is
Folate is the general name for a B vitamin found naturally in food and, as folic acid, in fortified foods and most supplements. The NIH Office of Dietary Supplements (ODS) explains that some supplements use a different form, 5-methyl-tetrahydrofolate (5-MTHF), which also goes by L-5-MTHF, L-methylfolate and methylfolate. These names describe the same nutrient, so "l methylfolate" and "methylfolate" on a label mean the same thing.
ODS says the bioavailability of 5-MTHF in supplements is the same as or greater than that of folic acid. That is the main reason some people choose it. It does not mean methylfolate works better for every purpose.
Methylfolate vs folic acid, and the MTHFR question
Many people look up methylfolate because they have heard about the MTHFR gene. A common variant (677C>T) lowers the body's ability to make 5-MTHF. ODS says about 25% of Hispanic people, 10% of Caucasian and Asian people and 1% of African American people carry two copies of it, and that research on whether these people benefit from taking 5-MTHF is inconclusive.
CDC is direct on this point. Its page says people with an MTHFR variant can process all types of folate, including folic acid. People with the TT genotype have blood folate levels about 16% lower on average at the same folic acid intake, but CDC says intake matters more than genotype. CDC addresses the claim that people with the variant should avoid folic acid and says plainly that it is not true.
For pregnancy planning, folic acid comes first. CDC says folic acid is the only type of folate shown to help prevent neural tube defects, and that anyone who could become pregnant should get 400 mcg of folic acid daily, even with an MTHFR variant. If you are looking at prenatal vitamins with methylfolate, check whether the label also lists folic acid, and ask your obstetric clinician. See our folic acid and prenatal vitamin guides.
How much folate you need, and the upper limit
ODS gives the Recommended Dietary Allowance (RDA) in micrograms of dietary folate equivalents (mcg DFE), which account for how well each form is absorbed.
| Group | RDA (mcg DFE per day) |
|---|---|
| Children 1 to 3 years | 150 |
| Children 4 to 8 years | 200 |
| Children 9 to 13 years | 300 |
| Teens 14 to 18 and adults | 400 |
| Pregnancy | 600 |
| Breastfeeding | 500 |
The upper limit (UL) for synthetic folate from supplements and fortified foods is 1,000 mcg a day for adults 19 and older and 800 mcg for ages 14 to 18. It is 300, 400 and 600 mcg for ages 1 to 3, 4 to 8 and 9 to 13. ODS does not set a separate UL for 5-MTHF, so use these numbers as your guide and let a doctor decide on anything higher.
Reading a methylfolate label. ODS notes there is no formal DFE conversion for 5-MTHF, and FDA lets makers use a factor of up to 1.7. So a label might show 400 mcg of methylfolate as 680 mcg DFE (400 times 1.7). Follow the label and compare products by the mcg DFE line.
What methylfolate supplements can and cannot do
The FDA does not approve dietary supplements for safety or effectiveness before they are sold. Be wary of methylfolate benefits that sound too broad.
- Depression. ODS says evidence on folate and depression is mixed. Some studies suggest 5-MTHF may have more promise than folic acid as an add-on to antidepressants. A meta-analysis of three trials found 15,000 mcg a day might be an effective add-on to SSRIs, but the evidence was low quality, and other trials found no benefit. ODS says doses this high exceed the UL and should be used only under medical supervision.
- Neural tube defects. As above, CDC says folic acid is the form shown to help.
Safety: vitamin B12 and medicine interactions
- Vitamin B12. ODS explains that large amounts of folate can correct the anemia of vitamin B12 deficiency but not the nerve damage, and may make some symptoms worse. Ask your doctor whether your B12 level should be checked, and consider a product that pairs methylfolate with B12. See our methylcobalamin guide.
- Methotrexate. People taking it for cancer should ask their oncologist before taking folate, ODS says.
- Seizure medicines. Phenytoin, carbamazepine and valproate can lower folate, and folate may lower their blood levels. Check with your provider first.
- Sulfasalazine. It reduces folate absorption; ask your provider how to handle folate.
FDA advises talking with a doctor, pharmacist or dietitian before starting any supplement.
How to choose a methylfolate supplement
- Form. Look for "L-methylfolate" or "5-MTHF" on the Supplement Facts panel.
- Amount. Check the mcg DFE number against the RDA for your age. More is not better.
- Quality mark. USP says its Verified Mark means a product contains the listed ingredients in the declared strength and amounts, does not contain harmful levels of specified contaminants, breaks down within a set time, and was made under FDA good manufacturing practices. It does not mean the product works.
- Kids. Methylfolate for kids should come only on a pediatrician's advice, within the age RDA and UL above.
What to look for when you buy
L-methylfolate capsule with the amount shown in mcg DFE
Best for: Adults who prefer the 5-MTHF form after checking with their doctor
ODS says 5-MTHF is absorbed as well as or better than folic acid. A label that states mcg DFE lets you compare it with the 400 mcg DFE adult RDA.
Watch out: Not shown to prevent neural tube defects; if you could become pregnant, you still need folic acid, per CDC.
See options on AmazonMethylfolate combined with vitamin B12 (methylcobalamin)
Best for: People who want folate and B12 in one product
ODS warns that large amounts of folate can hide the anemia of B12 deficiency while nerve damage continues. Pairing the two avoids taking folate alone.
Watch out: A combination is not a substitute for testing B12 if you have numbness, tingling or memory changes.
See options on AmazonPrenatal vitamin that includes folic acid
Best for: Anyone who could become pregnant, including people with an MTHFR variant
CDC says folic acid is the only form of folate shown to help prevent neural tube defects and recommends 400 mcg a day. If a prenatal lists methylfolate, check that it also lists folic acid.
Watch out: Check the label for the folic acid line and ask your clinician before taking more than one folate product.
See options on AmazonFolic acid 400 mcg tablet
Best for: People who simply need to meet the RDA, including MTHFR carriers
CDC says people with an MTHFR variant can process folic acid, and ODS says folic acid taken without food is almost fully absorbed.
Watch out: Stay within the UL of 1,000 mcg a day from supplements and fortified foods for adults unless your doctor advises more.
See options on AmazonQuestions people ask
- Is L-methylfolate the same as methylfolate?
- Yes. ODS lists L-5-MTHF, L-methylfolate and methylfolate as names for the same form of folate, 5-MTHF.
- Is methylfolate better than folic acid?
- It is absorbed as well as or better than folic acid, according to ODS. But CDC says folic acid is the only form shown to help prevent neural tube defects, and people with MTHFR variants can process it.
- Do I need methylfolate if I have an MTHFR variant?
- Not necessarily. CDC says the claim that MTHFR carriers should avoid folic acid is not true and still recommends 400 mcg of folic acid daily for anyone who could become pregnant. Ask your doctor about your situation.
- Can kids take methylfolate?
- Only if a pediatrician advises it. Children's folate needs and upper limits are much lower than adults', from 150 mcg DFE a day at ages 1 to 3.
- What are the side effects of too much methylfolate?
- The main concern ODS describes is that high folate intake can mask vitamin B12 deficiency. Folate can also interact with methotrexate, some seizure medicines and sulfasalazine.
Sources
- Folate: Fact Sheet for Health Professionals (ods.od.nih.gov), NIH Office of Dietary Supplements
- MTHFR Gene Variant and Folic Acid Facts (cdc.gov), Centers for Disease Control and Prevention
- FAQs: USP Verified Mark (quality-supplements.org), U.S. Pharmacopeia (USP)
- FDA 101: Dietary Supplements (fda.gov), U.S. Food and Drug Administration