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Folic acid (FA) remains the predominant folate source in prenatal multivitamins (PMVIs), but its conversion to active methyltetrahydrofolate (MTHF) varies among individuals, raising concerns about unmetabolized FA accumulation during pregnancy.
Prenatal multivitamins containing 6S-5-methyltetrahydrofolate prevent unmetabolized folic acid buildup during pregnancy while maintaining equivalent folate status
Folic acid (FA) remains the predominant folate source in prenatal multivitamins (PMVIs), but its conversion to active methyltetrahydrofolate (MTHF) varies among individuals, raising concerns about unmetabolized FA accumulation during pregnancy.
Excess FA exposure is increasingly linked with metabolic and clinical risks, heightening the need for safer, bioactive alternatives such as 6S-5-MTHF. Hence, researchers compared the efficacy of a 6S-5-MTHF–based PMVI with a FA formulation in preventing unmetabolized FA accumulation during a 24-week pregnancy period.
This 24-week, double-blind, randomized controlled trial involved 62 first-trimester pregnant women. Volunteers were assigned to receive a PMVI containing either 1000 mcg dietary folate equivalent (DFE) 6S-5-MTHF or 1360 mcg DFE FA (n=31 per arm). Dietary intake was assessed using standardized dietary recalls, and fasting blood samples were obtained at baseline, week 12, and week 24. Folate metabolites, including unmetabolized FA, were quantified using validated liquid chromatography–tandem mass spectrometry (LC-MS/MS) assays.
Plasma folate concentrations did not differ significantly between the two supplementation groups over time. By week 24, nearly one-third of participants in the FA group exceeded the established upper tolerable intake level (UL), whereas none in the 6S-5-MTHF group surpassed this threshold (p=0.001).
The frequency of detectable unmetabolized FA declined in the 6S-5-MTHF group but persisted in the FA group. At week 24, the FA arm demonstrated substantially higher rates and concentrations of unmetabolized FA than the 6S-5-MTHF arm (p<0.01).
The team of investigators concluded that use of a PMVI containing 6S-5-MTHF provided equivalent folate status while minimizing the risk of excessive FA intake and preventing the accumulation of unmetabolized FA in maternal serum.
Journal of the Academy of Nutrition and Dietetics
Prenatal Multivitamin with 6s-5-methyltetrahydrofolate Prevents Unmetabolized Folic Acid Accumulation During Pregnancy in a 24-week Double-blind, Randomized, Controlled trial
F. Draicchio et al.
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