Concern has been raised about the potential negative effects of unmetabolized folic acid (UMFA), but research on the safety of UMFA is lacking.
After consumption, folic acid must be converted into a usable form by the enzyme dihydrofolate reductase (DHFR). However, DHFR can become easily saturated, leading to a build-up of UMFA. The 2007–2008 National Health and Nutrition Examination Survey (NHANES) found that UMFA was detectable in >95% of Americans who provided serum samples.[1]. UMFA doesn’t behave like natural folate in the body and is generally thought to have no biological effects. However, exactly how UMFA interacts with the body is poorly understood, and it’s unclear whether there are any health risks with long-term exposure.[2]
Preliminary research has raised the concern that UMFA might negatively affect immune function and have an inhibitory effect on normal folate metabolism, but further research is needed.[3][4][5]