Vitamin B9 is crucial for a healthy pregnancy and newborns.
Although many women think of “folic acid” to prevent or reduce the risk of birth defects in their offspring, they should look for supplements featuring active folate — or 5-methyltetrahydrofolate (5-MTHF) — which is far more efficient.
Unlike folic acid, 5-MTHF is immediately recognised by the body. Folic acid undergoes conversion steps to become 5-MTHF.
However, approximately 40% of the global population has a genetic polymorphism that impairs this process, preventing them from converting folic acid to 5-MTHF and receiving the benefit.
As an essential nutrient for pregnant women, folate supports DNA synthesis, cell division and the proper neurological development of the foetus.
Folate is critical for the 140 million women who give birth each year — and their newborns.
Evidence supporting 5-MTHF for healthy pregnancies and fertility continues to grow.
New evidence
A 12-week study comparing the bioavailability of 5-MTHF (as Quatrefolic®) and folic acid in 96 pregnant women found favourable results for active folate.1
- Efficiency: Although each group received a comparable dose, 5-MTHF produced a greater increase in plasma folate status in maternal, foetal and placental blood samples, as well as decreases in plasma homocysteine with time.1
- Superior metabolism: The 5-MTHF group showed a significant increase in plasma folate concentrations and red blood cell folate (a marker of long-term status).1
- Reduced unmetabolised folic acid (UMFA): High UMFA levels are a growing concern in prenatal nutrition. 5-MTHF was associated with lower UMFA accumulation, offering a potential safety benefit.1
The authors concluded that prenatal vitamins containing 5-MTHF “may offer an efficacious alternative to those containing folic acid in the latter two trimesters of pregnancy as they reduce concentrations of UMFA in maternal and foetal tissues … without compromising total folate status.”1
This research aligns with another recent study on vitamin B9 forms. Although both folic acid and 5-MTHF supplementation achieved adequate folate status, the quality and efficiency of that status differed significantly.
Individuals consuming folic acid were substantially more likely to exhibit supranutritional folate levels (29% of participants) compared with 0% in the 5-MTHF group.
In this study, UMFA was present in 31% of the folic acid group compared with just 7% in the 5-MTHF group.2
These clinical results are supported by earlier pharmacokinetic data showing that a single dose of either HY-FOLIC® (a finished product containing Quatrefolic) has twice the bioavailability of folic acid — as indicated by much higher Cmax and AUCt for the active form (5-MTHF).3
Protecting hearts and pregnancies
Evidence also indicates that superior metabolism (lower UMFA) translates to better functional outcomes, such as homocysteine management.
Active folate is essential in managing homocysteine, especially during pregnancy.
High homocysteine levels (hyperhomocysteinemia) can impact pregnancy by causing epithelial dysfunction, increasing the risk of blood clots and impairing cellular growth.
Researchers demonstrated the capacity of 5-MTHF (400 μg of Quatrefolic plus B6 and B12) to lower homocysteine more effectively than a conventional vitamin with high-dose folic acid (5 mg/day).
The ideal homocysteine levels were achieved in 55.8% of participants.4
In the latest study involving 96 pregnant women, Quatrefolic was found to reduce plasma homocysteine, a marker of folate-dependent metabolism.1
Collectively, these study results reinforce the idea that active folate (5-MTHF) may be a superior form of vitamin B9 to folic acid in terms of metabolic efficiency.
This growing body of evidence supports 5-MTHF as a clinically effective and metabolically advantageous alternative to folic acid supplementation for healthy pregnancy.
References
- E. Ernawati, et al., Clin. Nutr. ESPEN. 76, 105107 (2026).
- F. Draicchio, et al., Front. Nutr. 13, 1679067 (2026).
- N. Nafrialdi and F.D. Suvarna, Int. J. Appl. Pharma. 16(6), 64–68 (2024).
- A. Mazza, et al., J. Biol. Regul. Homeost. Agents 30(3), 921–927 (2016).
