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Late Breaking/Rapid Science Oral Session

(LB04-05-25) Using Methyltetrahydrofolate Instead of Folic Acid in Prenatal Multivitamin Reduces Unmetabolized Folic Acid Levels in the Mother-Fetus Dyad: A Randomized Controlled Trial

Sunday, June 1, 2025
2:48 PM – 3:00 PM ET
Location: S230 CD
Objectives: Most prenatal multivitamins (PMVIs) contain the synthetic folic acid (FA), which needs to be reduced to methyltetrahydrofolate (MTHF) for use in vivo. Accumulation of unmetabolized FA (UMFA) in maternal and fetal tissues during pregnancy is a rising concern because it may interfere with folate metabolizing enzymes and receptors. This study examined whether using 6S-5-MTHF instead of FA in a PMVI prevents unmetabolized FA (UMFA) accumulation in maternal and fetal tissues.

Methods: Sixty-two first-trimester pregnant women were recruited and received a PMVI containing 1000 mcg DFE 6S-5-MTHF or 1360 mcg DFE FA for 24 weeks (n=31 per group). Fasting blood samples were collected at week 0, 12, and 24 and cord blood and placental samples were collected at delivery. Folate metabolites were measured with LC-MS/MS.

Results: By week 24 of the study, there were significantly fewer participants (7% versus 31%) with detectable UMFA and lower average UMFA levels in maternal blood of the 6S-5-MTHF group versus the FA group (p < 0.01). UMFA was detected in all placentas collected from the PMVI with FA group, significantly more than the PMVI with 6S-5-MTHF group (p < 0.01). Accordingly, the average UMFA content was lower in the PMVI with 6S-5-MTHF group than the PMVI with FA group accordingly (p < 0.01). Few cord blood samples (n = 2) had UMFA detected and both of them were from the FA group. By contrast, maternal and fetal MTHF and total folate levels did not differ between groups.

Conclusions: PMVI with 6S-5-MTHF may be a safer alternative to FA because it prevents UMFA accumulation in maternal and fetal tissues while not compromising total folate levels.

Funding Sources: This study was supported by Ritual (Natals. Inc)