Is folic acid still effective if you have a MTHFR polymorphism?

Folic acid at a sufficient dose should still increase folate levels regardless of a methylenetetrahydrofolate reductase (MTHFR) polymorphism, although the response may be slightly less than in someone without an MTHFR polymorphism.^[1]

MTHFR is the key rate-limiting enzyme required for the conversion of folic acid into L-methylfolate, the main active form of folate in the body. MTHFR is prone to genetic mutations called single-nucleotide polymorphisms (SNPs) which can reduce the functioning of the enzyme, leading to impaired production of L-methylfolate and lower overall folate levels.^[2][3] Accordingly, people with MTHFR polymorphisms have an increased need for folate.

Approximately 25% of the global population has an MTHFR polymorphism, and these polymorphisms are associated with an increased risk of various medical conditions including heart and blood vessel disease, infertility, certain types of cancer, and NTDs.^[4][1] However, there’s evidence that when folate levels are adequate, disease risk may be the same as for those without MTHFR mutations.^[5] When comparing how people with and without MTHFR polymorphisms respond to folic acid supplementation, people with polymorphisms do see a slightly lower increase in plasma folate levels. Still, folate increases to an adequate level regardless.^[1]

Supplementing with L-methylfolate bypasses MTHFR and may be more efficient at raising folate levels in people with MTHFR polymorphisms, but this supplemental form of folate is much less researched than folic acid.