Bioavailability and intake of folic acid in infants depend on folic acid levels

09.2025
Author Dr. Martin Claßen, Bremen

Folic acid is an essential nutrient because methylation processes and nucleotide biosynthesis depend on it, and amino acid metabolism is influenced by it. Some people do not get sufficient folate from their diet, which is why foods rich in folic acid are recommended and folic acid supplements are sold. Infant formulae are also enriched with folic acid or with (6S)-5-methyltetrahydrofolate calcium salt (5-MTHF-Ca). It is unclear which of the two forms of supplements offer better bioavailability and whether absorption of folic acid or 5-MTHF-Ca depends on the folic acid level.
Two formulae were tested against each other in a prospective study of 240 healthy Serbian newborns: one formula contained 78 μg/100 g milk powder (or 15.2 μg/100 kcal) or an equimolar quantity of 5-MTHF-Ca (81 μg/100 g milk powder or 15.8 μg/100 kcal). The respective formula was given to the children from the age of 20.5 (SD 3.6) days up to the age of 16 weeks. The study analysed a subgroup of 167 children, measuring their folic acid levels at the beginning and end of the observation period. A statistical model was used in the analysis to investigate the extent to which the resulting folic acid level depends on the nature of the supplement, the length of substitution and the basal folic acid concentration in the erythrocytes.
The data shows that the increase in folic acid level was more pronounced when the children had lower levels at the start of the study. This effect also depended on the nature of the folic acid supplement used. 5-MTHF-Ca resulted in a more significant increase in the erythrocyte level, and the reduction in bioavailability with higher blood levels was lower. This is likely to be caused by the binding of the supplement to the specific transporter PCFT.

Comment: Even before it was found that folic acid supplements for pregnant women help reduce the rate of neural tube defects, we knew that folic acid is essential for growing organisms and that people may not get enough of it even in our affluent society. This study improves our knowledge of the physiology of folic acid intake in infants and can help us optimise future supplementation strategies. 5-MTHF-Ca may be beneficial here thanks to its high bioavailability, though the study did not measure clinical endpoints. Separate studies would be required for this, to also determine whether the results can be generalised for older children and adults.
 

Reference:
Obeid, R et al. Dependence of bioavailability of folic acid and (6S)-5-methyltetrahydrofolate on baseline red blood cell folate concentrations in infants. Human Nutrition & Metabolism, Vol. 42, 2025, 200335. DOI: 10.1016/j.hnm.2025.200335